April 1 2004   Hello Valerie Duffy, Madeleine Sigman-Grant, Maggie Powers,

Despite the date, it is no joke that aspartame is 11% methanol, immediately
released into the GI tract, and within hours converted by the liver into
formaldehyde and formic acid-- potent cumulative toxins that attack every
tissue and trigger hypersensitivity reactions.

The exponentially ever expanding network of science makes it increasingly
evident that this is so.  The house of cards of three decades of denial is
exceedingly unstable, liable to implosion this year.  Indeed, this very
communication is evidence of that.

For five years, as a volunteer layman activist, concerned to serve the
public welfare by supplying civil, lucid, detailed, long, referenced reviews
of mainly mainstream scientific research, I have never had any genuine
two-way communication with anyone on the pro-aspartame side.  I now have an
impulse to send this, sensing that female professionals can not help but act
from the deepest core of their being to actually protect people.

Here is an opportunity to alert families all over the world about an easily
avoidable scourge.  Here is an opportunity to mobilize responsible, capable,
flexible, caring professionals to make the best of an increasingly
difficult, rapidly unstable situation that affects hundreds of thousands of
jobs, the fortunes of great corporations, and public trust in government
worldwide.  Why, like the heedless tobacco industry, continue to march
blindly down a closed corridor that leads to decades of perilous, boring,
humiliating, and exceedingly hazardous legal and financial difficulties,
while needless disease , disability, and death wreck rampant and careless
harm on individuals and societies?

Why not come clean, admit the disaster, apologize, warn the peoples of our
single human family, cease production, sales, and distribution of aspartame
and MSG, and set aside hundreds of billions of dollars into a fund to fairly
recompense the hapless victims and to research alternatives, like stevia,
that hold promise of being a wholly benign solution?  Wouldn't this be fun?
Wouldn't this set an outstanding historical precedent for dealing with
similar situations, as serious, as simmering, just as ready to boil over?
Why can't we cooperate reasonably, daringly, and creatively as free citizen
souls of this wonderful, tortured single world polity?   Wouldn't this be
true democratic action?  Wouldn't this be spiritual service?

I say this to you now, and you do hear me.  You must listen to the truth
within yourself.  Whatever you do, the fact stands and expands inevitably
that this message is said widely, and heard widely.  Truth can not be
managed.  It is essential that you scrutinize the evidence herein and
rethink the entire situation.  Your fate is in your own thinking, nowhere
else.

In mutual service,  Rich Murray

http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review by American Dietetic Association Feb 2004,
Valerie B. Duffy & Madeleine Sigman-Grant: Murray 4.1.4 rmforall

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

[ My critical comments are in square brackets.  I've copied parts of another
recent critique after the end of this critique, and then supplied more
references and links.  I have spaced the lines to make the text a little
easier to comprehend, without changing anything else.
Two similar previous ADA position statements are referenced for 1998 and
1993, both widely cited.
I make a few comments about neotame, a derivative of aspartame.
The journal letter by Anthony Kulczycki competently shows the flaws in the
inadequate effort by Geha et al.
I also draw attention to very interesting results by Yu F. Sasaki's team,
which have aroused remarkably little comment:

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]    ]
************************************************************

American Dietetic Association, 120 South Riverside Plaza, Suite 2000,
Chicago, IL 60606-6995      Phone: (800) 877-1600, ext. 5000
www.eatright.org        sales@...

http://www.eatright.org/Nutritive(1).pdf
J Am Diet Assoc. 2004 Feb; 104(2): 255-75.
Position of the American Dietetic Association: use of nutritive and
nonnutritive sweeteners. American Dietetic Association.
[ p. 275 lists 2 authors and 10 reviewers:
ADA position adopted by the House of Delegates on October 18, 1992, and
reaffirmed on September 6, 1996 and on June 22, 2000.
This position will be in effect until December 31, 2009.
ADA authorizes republication of the position statement/support paper, in its
entirety, provided full and proper credit is given.
Requests to use portions of the position must be directed to ADA
Headquarters at 312/899-0040, ext. 4835, or  ppapers@...   .

Authors:
Valerie B. Duffy, PhD, RD (University of Connecticut, Storrs, CT) [  Valerie
Duffy Assc. Prof.   Organization:  ALLIED HLTH DIETETICS   Status:  Faculty
Building:  KOONS HALL   UBox:  UNIT 2101   Email:  VALERIE.DUFFY@...
Web URL:  M.UCONN.EDU/~VDUFFY/   Phone:  860 486-1997 ];
Madeleine Sigman-Grant, PhD, RD (University of Nevada Cooperative Extension,
Las Vegas, NV, [  http://www.jneb.org/boe/sigman.htm
  MCH Nutrition Specialist and Professor, Cooperative Education,
University of Nevada-Reno, 2345 Red Rock Street, Las Vegas, Nevada
89146-3160   Phone 702-222-3130   msigman@...  ]

Reviewers:
Margaret A. Powers, MS, RD, CDE, International Diabetes Center, Park
Nicollet Institute, Minneapolis, MN, Diabetes Care and Education Dietetic
Practice Group, [ Maggie Powers, Powers and Associates Inc, "a health
communications firm" , " Margaret is president of Powers and Associates,
Inc., a national health and nutrition communications firm.", St. Paul, Minn.
Minnesota Dietetic Association  mda@... ,  Maggie Powers
651-699-0031 mpowers5@... , http://www.parknicollet.com/Institute/   Park
Nicollet Institute, 3800 Park Nicollet Blvd., Minneapolis, MN 55416 
952-993-3350 ,
http://www.parknicollet.com/Diabetes/   International Diabetes Center,
3800 Park Nicollet Boulevard, Minneapolis, Minnesota 55416-2699
Phone: 952-993-3393  Toll-free: 1-888-825-6315  Fax: 952-993-1302
idcdiabetes@...   1-888-637-2675.   ] ;
Denise Elmore, DTR, University of Texas MD Anderson Cancer Center, Houston,
TX, Dietetic Technicians in Practice Dietetic Practice Group;
Esther F. Myers, PhD, RD, FADA (American Diebetic Association, Chicago, IL);
Diane Quagliani, MBA, RD (Quagliani Communications, Inc., Western Springs,
IL);
Gita Patel, MS, RD, CDE, Nutrition Consultant, Etna, NH, Sports,
Cardiovascular and Wellness Dietetic Practice Group;
Marie Spano, MS, RD, Atlanta, GA. Sports, Cardiovascular and Wellness
Dietetic Practice Group;
Kimberly F. Stitzel, MS, RD (American Dietetic Association, Washington, DC);
Sue Taylor, MS, RD (Kellen Company, Atlanta, GA); and
[ADA] Association Positions Workgroup:
Robert Earl, MPH, RD (chair);
Sonja Connor, MS, RD.  ]

Sweeteners elicit pleasurable sensations with (nutritive) or without
(nonnutritive) energy.
Nutritive sweeteners (eg, sucrose, fructose) are generally recognized as
safe (GRAS) by the Food and Drug Administration (FDA), yet concern exists
about increasing sweetener intakes relative to optimal nutrition and health.
Dietary quality suffers at intakes above 25% of total energy (the Institutes
of Medicine's suggested maximal intake level). In the United States,
estimated intakes of nutritive sweeteners fall below this, although one in
four children (ages 9 to 18 years) can surpass this level.
Polyols (sugar alcohols), GRAS-affirmed or petitions filed for GRAS, add
sweetness with reduced energy and functional properties to foods/beverages
and promote dental health.
Five nonnutritive sweeteners with intense sweetening power have FDA approval
(acesulfame-K, aspartame, neotame, saccharin, sucralose) and estimated
intakes below the Acceptable Daily Intake (level that a person can safely
consume everyday over a lifetime without risk).
By increasing palatability of nutrient-dense foods/beverages, sweeteners can
promote diet healthfulness.
Scientific evidence supports neither that intakes of nutritive sweeteners by
themselves increase the risk of obesity nor that nutritive or nonnutritive
sweeteners cause behavioral disorders.
However, nutritive sweeteners increase risk of dental caries.
High fructose intakes may cause hypertriglyceridemia and gastrointestinal
symptoms in susceptible individuals.
Thus, it is the position of The American Dietetic Association that consumers
can safely enjoy a range of nutritive and nonnutritive sweeteners when
consumed in a diet that is guided by current federal nutrition
recommendations, such as the Dietary Guidelines for Americans and the
Dietary References Intakes, as well as individual health goals.
Dietetics professionals should provide consumers with science-based
information about sweeteners and support research on the use of sweeteners
to promote eating enjoyment, optimal nutrition, and health.
Publication Types: Guideline  PMID: 14760578
*************************************************************

http://www.findarticles.com/cf_dls/m0887/n6_v17/20848372/p1/article.jhtml
Valerie B. Duffy and G. Harvey Anderson, Position of The American Dietetic
Association: Use of Nutritive and Nonnutritive Sweeteners, J. American
Dietetic Assoc 98(5): 580-587 (May 1998)

http://www.geocities.com/HotSprings/2455/sugar.html
"Position of The American Dietetic Association: Use of Nutritive and
Non-Nutritive Sweeteners," Journal of The American Dietetic Association, 93:
7: 816-821, July 1993.  Franz, M. J., Maryniuk, M. D.
*************************************************************

p. 263  "Aspartame, a dipeptide (L-a-aspartyl-L-phenylalanine methyl ester)
is 160 to 220 times sweeter than sucrose.
Intestinal esterases hydrolyze aspartame to aspartic acid, methanol, and
phenylalanine (74).
These components are found in much greater amounts in the normal diet in
fruits, vegetables, meat, and milk.  [ standard industry PR spin ]
For example, a serving of nonfat milk provides about six times more
phenylalanine and 13 times more aspartic acid, whereas a serving of tomato
juice has about six time more methanol than an equal volume beverage
sweetened 100% with aspartame (75).
The amino acids are metabolized to provide 4 kcal/g.
Thus, this sweetener does provide energy; however, because of the intense
sweetness of aspartame, only minute amounts need to be added, and the amount
of energy derived is negligible.

[  To summarize the actual and simple reality:

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE. [ an aspartame industry lab ]
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [ This data is the
average of 4 monkeys. ]

In 1981, the FDA approved aspartame as a sweetener for a number of dry uses
(eg, tabletop sweetener, cold breakfast cereal, gelatins and puddings) and
in chewing gum.
This approval was expanded in 1983 to include carbonated beverages.
The Council on Scientific Affairs of the American Medical Association in
1985 concluded that, "Available evidence suggests that consumption of
aspartame by normal humans is safe and not associated with serious adverse
health effects." (76).  [  Note the cautious qualifiers "available",
"suggests", "normal", "serious".  ]
In 1996, the FDA approved aspartame as a "general purpose sweetener" for use
in all foods and beverages.
Aspartame is also approved for use in over 100 nations.

[   http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 7.10.0 rmforall

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9: rmforall

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2 rmforall  ]

The United Nations leads the world in demand for aspartame, accounting for
up to 75% of sales.
Although soft drinks account for above 70% of aspartame consumption, this
sweetener is added to more than 6,000 foods, personal care products, and
pharmarceuticals.
Aspartame is available in liquid, granular, encapsulated, and powder forms
to extend use in food and beverage products.
Aspartame decomposes during excessive heating and loses its sweetening
power.
However, appropriate cooking methods can minimize losses of aspartame
sweetness (77).

Detailed studies have been conducted to determine how ingestion influences
plasma levels of aspartic acid, phenylalanine, and methanol (or the
byproduct formate).  [ Typical of industry PR spin, the alarming fact that
formaldehyde is another inevitable byproduct is omitted. ]
In studies with healthy adults (78), levels of plasma aspartate
concentrations or blood levels of formate did not change with a bolus load
up to four times the ADI for aspartame (ie, 200 mg/kg).  [ The issue is not
blood or plasma levels, but the cumulative levels of formaldehyde and formic
acid toxic products in a variety of body tissues, resulting from long-term,
heavy use (above 6 12-oz cans daily diet soda, about 2L) by many types of
vulnerable persons. ]
Plasma phenylalanine response to aspartame (as well as to other dietary
sources of phenylalanine) varies in persons with phenylketonuria  (PKU), a
homozygous recessive inborn error of metabolism of which affected
individuals cannot metabolize phenylalanine.
In persons with this rare (frequency in approximately one in 10,000 whites)
[  ie, 1,000  in 10 million,  10,000 in 100 million,    30,000 in 300
million ] inborn error, excess intake of this amino acid can cause higher
plasma phenylalanine levels and its adverse effects (79).
MNT involes the control of dietary sources of phenylalanine, including
aspartame.
The FDA requires that foods that contain aspartame have the prominent
display of the following label:
"PHENYLKETONURICS: CONTAINS PHENYLALANINE" (80).

Untreated individuals with PKU appear to tolerate the amount of
phenylalanine in a diet soda sweetened with aspartame (approximately 104
mg/12 oz) (81).
Heterozygotes for PKU do not show changes in cognitive performance or in
electroencephalograms after 12 weeks of consuming either 15 or 45 mg/kg
bw/day of aspartame (82).   [ milligrams per kilogram body weight per day ]
In non-PKU individuals, single-bolus studies of aspartame (up to 50 mg/kg
bw) or repeat dose studies show a plasma phenylalanine response near the
normal postprandial range and considerably lower than that observed in PKU
individuals or those with mild hyperphenylalanemia (78).

Aspartame breaks down to diketopiperazine [ a potent carcincogen ] in liquid
systems with excessive heat exposure.  Animal toxicity studies show that,
even if all aspartame were converted to diketopiperazine in beverages, the
amount would be well below the FDA-established ADI of 3,000 mg/kg bw/day for
this compound (83).

Some individuals report allergic reactions to aspartame, including edema of
the lips, tongue, and throat; dermatologic reactions; and respiratory
problems (84).
[ These are classic formaldehyde allergic reactions.  It is typical that
industry research never explores which breakdown products of aspartame might
be causing allergic reactions.  The disparaging term "some individuals" is
used rather than give specific numbers.  Russell M. Jaffe, MD, PhD found 20
% of fibromyalgia patients were sensitive to aspartame:

http://www.perque.org/Fibromyalgia.pdf
A Novel Treatment for Fibromyalgia Improves Clinical Outcomes in a
Community-Based Study.
Patricia A. Deuster, Russell M. Jaffe.
Journal of Musculoskeletal Pain. 1998; Vol. 6(2): 133-149.

"Using blood tests, the researchers ran a panel of 350 antigens including
environmental chemicals, food additives and preservatives, crustaceans,
diary products, fish, fruits, grains, meats, mollusks, and oils."

"Normal, healthy people react to only two or less of this panel. The
greatest offenders were:

MSG                             42.5 % (17 out of 40 patients)
Candida albicans            37.5 %
Caffeine                          37 %
Chocolate/cocoa             37 %
Food colorings                37 %
Cola beverages                37 %
Cow Dairy Products        25 %
Sulfite/metabisulfite           22.5%
Xylene                             22.5%
Yogurt                             22.5%
Aspartames                      20%
BHA                                20%
Cadmium                          20%
Lead                                 20%
Tylenol                              20%
Yeast                                20%
Sodium benzoate               20%
Orange                              20%                     "

http://www.perque.com/    info@...  800-525-7372

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.    toxicology@...
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall    ]

However, two double-blinded challenge studies report difficulty in
recruiting individuals who claim an allergic respnse to aspartame and a
failure to reproduce the allergic reactions in controlled experimental
conditions (85, 86).
[ A number of standard aspartame industry ploys apply here.  Again and
again, industry funded double-blind laboratory tests are used to justify
ignoring negative clinical feedback.  It happens to be very easy to conduct
misleading double-blind laboratory studies:
by using only healthy subjects, by using too few subjects to generate
statistics that could detect effects rarer than 1% incidence,
by giving the aspartame in delayed release capsules, rather than in fast
release beverages,
by using one-time or limited duration exposures that can not detect
long-term accumulation  and gradual sensitivation, and,
as always, failing to measure the actual disposition of the accumulation of
toxic formaldehyde and formic acid products over time in many specific
tissues.
After the references for this ADA statement, I give the full text of a
journal letter (Feb 1995) by Prof. Anthony Kulczycki, Jr of Washington
University School of Medicine, that gives a detailed critique of reference
(86), the Geha study (1993) .    In general, aspartame industry research and
review papers barely mention  that many competent negative laboratory
studies do exist.

http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity 6.4.1 rmforall   four double-blind studies

Headache 1988 Feb;28(1):10-4
The effect of aspartame on migraine headache.
Koehler SM, Glaros A     PMID: 3277925, UI: 88138777
Shirley  M. Koehler, PhD   904-858-7651   skoehler@...
http://www.med.umich.edu/abcn/alpha/alpha-K.html#Koehler
Alan Glaros  glarosa@...  816-235-2074

They conducted a double-blind study of patients, ages 18-55, who had
a medical diagnosis of classical migraines (normally having 1-3
migraines in 4-weeks), who were not on medications (other than
analgesics), and who suspected that aspartame had a negative effect on
their migraine headaches. The subjects were given 1200 mg daily,
aspartame or placebo, for four weeks, about 17 mg/kg.  The placebo
group had no increase in headaches.  Approximately half of the subjects
(5 of 11) who took aspartame had a large, statistically significant
(p = 0.02), increase in migraine headache frequency, but not in
intensity or duration, compared to baseline or placebo.  Only 11 of
25 subjects completed the program: 8 dropped out, 4 began new
medications, 2 had incomplete records.  They were at home.
Since 1/3 of the subjects dropped out, they may have been choosing
to avoid headaches-- were they unpaid?  To achieve statistical
signifance with only 11 subjects hints that the incidence rate from
aspartame is very high, about 1/2,  for migraine cases who believe
that they are hurt by aspartame.

Walton, RG, "Adverse reactions to aspartame: double-blind challenge in
patients from a vulnerable population," 1993,  with Robert Hudak and
Ruth J. Green-Waite,  Biological Psychiatry, 34 (1), 13-17.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown,
OH 44501    330-740-3621    rwalton193@...
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

Eight depressed patients, ages 24-60, and five non-depressed controls,
ages 24-56, employed at the hospital, were given for 7 days either
aspartame or a placebo, and then after a 3 day break, given the
opposite.  Each got 2100 mg  aspartame daily, 30 mg/kg bodyweight,
equal to 10-12 cans of diet soda daily, about a gallon.  Despite the
very small number of subjects, the results were dramatic and
statistically significant.  The eight depressed patients reported with
aspartame, compared to placebo, much higher levels of nervousness,
trouble remembering, nausea, depression, temper, and malaise. (For each
symptom, p<0.01)  The five normals did not report strong enough
differences between aspartame and placebo to be significant.
Initially, the study was to be on a group of 40, but was halted by the
Institutional Review Board because of severe reactions among 3 of the
depressed patients.

Again, statistical significance with only 8 depressed patients:
"In this study, patients most often began to report significant
symptoms after day 2 or 3."  The incidence rate is very high,
indeed, about 1/3.  The most common symptoms are entirely typical
of thousands of case histories.

Stephen K. Van Den Eeden, T.D. Koepsell, W.T. Longstreth, Jr,
G. van Belle, J.R. Daling, B. McKnight, "Aspartame ingestion and
headaches: a randomized crossover trial," 1994, Neurology, 44, 1787-93
Steven K. Van Den Eeden,PhD  550-450-2202  skv@...
Division of Research, Kaiser Permanente Medical Care Program
3505 Broadway, Oakland, CA 94611-5714
http://www.dor.kaiser.org/dorhtml/investigators/Stephen_Van_Den_Eeden.html

In their introduction, they comment:

"In addition, the FDA had received over 5,000 complaints as of July,
1991 in a passive surveillance system to monitor adverse side effects.
(17)  Neurologic problems constitute the primary complaints in these
and several other case series, with headaches accounting for
18 to 45 %,depending on the case series reported. (17-19)"

Subjects, ages 18-57, were recruited who believed they got headaches
from aspartame, but were otherwise mentally and physically healthy.
They were paid $ 15 total, and were at home. Of the 44 subjects, 32
contributed data to the 38-day trials: a week of inert placebo, a week
of either aspartame or placebo, followed by a week of the opposite, and
then this two-week cycle repeated.  The daily dose was about 30 mg/kg.
"The proportion of days subjects reported having a headache was
higher during aspartame treatment compared with placebo treatment
(aspartame = 0.33, placebo = 0.24; p = 0.04) (table 5)".
Of the 12 subjects not included in the data, 7 reported adverse
symptoms before withdrawing.

Again, statistical significance with a moderate number of healthy
subjects, willing to be recruited by a newspaper ad, who believed
aspartame hurt them.  The number of headaches for each subject
for each treatment week are given: it appears that 4 subjects
had the strongest increase in headaches from the run-in week
or placebo week to their first week on aspartame, jumping from 0 to 5,
1 to 6, 1 to 4, 0 to 5 headaches per week.  So, about 4 of the 44
healthy people recruited for the study, who believed aspartame hurt
them, had a stong increase in headaches from the first week of daily
asparame exposure, while 7 reported adverse symptoms before leaving,
a total of 11 out of 44, an incidence ratio of 1/4.

This is sky high, if we consider that, if the incidence ratio for the
about two hundred million users in the USA is 1 of 100, that is 2
million cases.  It is plausible that the incidence ratio lies between 1
and 10 out of 100 for continuous daily exposure.  These three flames
should have set off alarm bells, with extensive follow-up studies and
much more careful study of thousands of case histories.  But these
little flares were adroitly smothered by thick blankets of industry
funded fluff.

http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers:
aspartame toxicity 6.4.1 rmforall    two double-blind studies

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research 7.31.2 rmforall

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"  Mark D. Gold

"Survey of aspartame studies: correlation of outcome and funding
sources," 1998, unpublished:   http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed
medical literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100%) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91%)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown,
OH 44501    330-740-3621    rwalton193@...
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm    ]

The FDA increased  the ADI for aspartame to its present level of 50 mg/kg
bw/day when it was approve for use in carbonated beverages in 1983 (87).
This ADI would approximate a 60-kg individual consuming 500 to 600 grams of
sucrose per day over a lifetime based on sweetness of aspartame compared
with that of sucrose (75).
Postmarket assessment of aspartame conducted between July 1991 and June 1992
shows that daily intake of aspartaame is below this ADI (88):

Aspartame eaters (at least 90th percentile of consumption) in the
general population consume 6% of the ADI    (3.0 mg/kg bw/day),
those 0 to 5 years of age consume  0.4%       (5.2 mg/kg bw/day),
people with diabetes consume 6.6%               (3.3 mg/kg bw/day), and
women of childbearing age consume 8.4%      (4.2 mg/kg bw/day).

As a tabletop sweetener, packets contain 35 to 40 mg of aspartame and are
equivalent to the sweetness of 2 teaspoons of sugar.
Consumers would need to contact individual companies to determine the amount
of aspartame in each product.
The amount in some common foods is as follows:

up to 225 mg in a 12-oz diet soda,
100 mg in an 8-oz drink made from powder,
80 mg in an 8-oz yogurt or a 4-oz gelatin dessert, and
up to 47 mg in frozen dairy products.

To reach the ADI, an 18-kg child (nearly 40 pound) child would need to
consume 900 mg of aspartame per day, which translates to
24 packets of sweetener (equivalent to 48 teaspoons of sugar),
four 12-oz cans of diet soda, or
nine 8-oz glasses of fruit drink made from a powder.

A comprehensive review of the safety of aspartame has recently been
published (75).
The review covers previous publications as well as new information that
support the safety of aspartame as a food additive and negates claims of its
association with a range of health problems includings brain tumors.
The SCF (89) has also recently evaluated new scientific evidence.
They conclude that current intakes in European countries are well below the
ADI set of JECFA and SCF (40 mg/kg bw/day),  that aspartame is not a
carcinogen and is not associated with neurobehavioral disorders, and thus
that there is no need to revise the risk assessment of, or ADI for,
aspartame.
[ You may not have noticed that the European ADI is 20% lower than the USA
level, or known this:

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall  EU Scientific Committee on Food, a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame (12.4.2): 59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M  ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo.  Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male)  alemany@...

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ].  Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@...    919-684-3303, 660-5657
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall ]

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall   ]

[ The ADA article goes on to devote several long paragraphs to neotame, a
derivative of aspartame, approved in Australia/New Zealand in summer 2000,
and by the USA FDA in summer, 2002-- yet which has, as far as I can search
out, never been put on the market anywhere in the world.  Since it is 40
times sweeter than aspartame, 40 times less of it is necessary, and so it
supplies 40 times less methanol, formaldehyde, and formic acid.   However,
of the "113 preclinical, clinical, and special studies and an additional 32
exploratory and screening studies", precisely no safety studies have been
independenty funded  and exactly one safety study has been  published in a
mainstream, peer-reviewed public access journal.  The FDA has relied
entirely on secret research by industry paid researchers.  If the research
was so good, and neotame is so safe and wonderful and worth billions of
dollars of yearly business, why hasn't the industry sagely hastened to place
their scores of studies in mainstream public research journals, and thereby
boost the public reputations of their expensive scientists?

http://groups.yahoo.com/group/aspartameNM/message/860
FDA: objections to neotame approval  (Section A) : Murray 8.4.2 rmforall

Regul Toxicol Pharmacol. 2003 Oct; 38(2): 144-56.
Long-term food consumption and body weight changes in neotame safety studies
are consistent with the allometric relationship observed for other
sweeteners and during dietary restrictions.
Flamm WG, Blackburn GL, Comer CP, Mayhew DA, Stargel WW.
AAC Consulting Group, Vero Beach, FL, USA

In long-term safety studies with neotame, a new high-intensity sweetener
7000-13,000 times sweeter than sucrose, the percent changes (%Delta) in body
weight gain (BWG) in Sprague-Dawley rats were several-fold greater than the
%Delta in overall food consumption (FC).
This study investigates the question of whether the changes in BWG were
adverse or secondary to small, long-term decrements in FC.
The hypothesis tested in Sprague-Dawley rats was that the relationship
between long-term %Delta in FC and %Delta in BWG is linear and in a ratio of
1:1.
The %Delta in FC were compared to %Delta in BWG after 52 weeks on study in
one saccharin (825 rats), two sucralose (480 rats), two neotame (630 rats),
and five dietary restriction (>1000 rats) studies.
Non-transformed plotting of data points demonstrated an absence of linearity
between %Delta in FC and %Delta in BWG; however, log-log evaluation
demonstrated a robust (R2=0.97) linear relationship between %Delta in FC and
%Delta in BWG.
This relationship followed the well-known allometric equation, y=bxa where x
is %DeltaFC, y is %DeltaBWG, b is %DeltaBWG when DeltaFC=1, and a is the
log-log slope.
Thus, in Sprague-Dawley rats at week 52, the long-term relationship between
%Delta in FC and %Delta in BWG was determined to be:
%DeltaBWG=3.45(%DeltaFC0.74) for males and %DeltaBWG=5.28(%DeltaFC0.68) for
females.
Sexes were statistically different but study types, i.e., the high-intensity
sweeteners saccharin and sucralose versus dietary restriction, were not.
The %Delta in BWG are allometrically consistent with the observed %Delta in
FC for these high-intensity sweeteners, including neotame. BW parameters are
not appropriate endpoints for setting no-observed-effect levels (NOELs) when
materials with intense taste are admixed into food.
An approach using objective criteria is proposed to delineate BW changes due
to toxicity from those secondary to reduced FC.  PMID: 14550756    ]

[ cited references ]
74. Ranney R, Oppermann J, Muldoon E, McMahon F.
Comparative metabolism of aspartame in experimental animals and humans.
J Toxicol Environ Health. 1976; 2: 441-1.  [ Twenty-eight years ago, an
aspartame industry lab proved 30% retention of toxic products (indubitably
formaldehyde and formic acid) of methanol from a single low dose of
aspartame in 4 monkeys.  No humans were tested for methanol product
retention in tissues, then or ever since.  Obviously, this would be
devastating to billions of dollars of yearly sales worldwide.

75. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL,
de Sonneville LM, Geha RS, Hertelendy Z, Koestner A, Leon AS, Liepa GU,
McMartin KE, Mendenhall CL, Munro IC, Novotny EJ, Renwick AG, Schiffman SS,
Schomer DL, Shaywitz BA, Spiers PA, Tephly TR, Thomas JA, Trefz FK.
Aspartame: Review of Safety.
Regul Toxicol Pharmacol. 2002; 35: S1-S93.   [ an industry funded and
staffed organ ]

76. Council on Scientific Affairs.
Aspartame: Review of safety issues.
JAMA. 1985; 254: 400-402.
[ http://www.ama-assn.org/ama/pub/category/1800.html
American Medical Association Council on Scientific Affairs: no reports
listed before 1994 ]

77.  Equal Sweetener.
Available at: www.equal.com
Accessed February 26, 2003.

78. Stegink L, Filer L J.
Effects of aspartame ingestion on plasma aspartate, phenylalanine, and
methanol concentrations in normal adults.
In: Tschanz C, Butchko H, Stargel W., Kotsonis F, eds.
The Clinical Evaluation of A Food Additive. New York, NY: CRC Press; 1996.
[ The term "food additive" is typical, because, unlike a "drug", the
industry does not have to prove safety or collect complaints from users and
physicians.  As usual for industry studies, the amount of accumulation over
long periods of exposure of toxic products of formaldehyde and formic acid
in many specific tissues are not studied. ]

79. Wolf-Novak LC, Stegink LD, Brummel MC, Persoon TJ,  Filer LJ Jr, Bell
EF, Ziegler EE, Krause WL.
Aspartame ingestion with and without carbohydrate in phenylketonuric and
normal subjects: effects on plasma concentrations of amino acids, glucose,
and insulin.
Metabolism. 1990; 39: 391-396.

80. Food and Drug Administration.
Food additives permitted for direct addition to food for human consumption:
Aspartame.
2002.  21CFR172.804.

81. Mackey S, Berlin CJ.
Effect of dietary aspartame on plasma concentrations of phenylalanine and
tyrosine in normal and homozygous phenylketonuric patients.
Clin Pediatr. 1992; 31: 394-399.

82. Trefz F, De Sonneville L, Matthis P, Benninger C, Lanz-Englert B,
Bickel H.
Neuropsychological and biochemical investigations in heterozygotes for
phenylketonuria during ingestion of high dose aspartame (a sweetener
containing phenylalanine)
Hum Genet. 1994. 93: 369-374.

83. Food and Drug Administration.
Food additives permitted for direct addition to food for human consumption:
Aspartame.
Federal Register. 1983; 48: 31376-31382.

84. Health Hazard Evaluation. Summary of Adverse Reactions Attributed to
Aspartame.
Washington, DC: US Dept of Health and Human Services; April 20, 1995.

85. Garriga M, Berkebile C, Metcalfe D.
A combined single-blind, double-blind, placebo-controlled study to determine
the reproducibility of hypersensitivity reactions to aspartame.
J Allergy Immunol. 1991; 87: 821-827.

86. Geha R, Buckley C, Greenberger P, Patterson R, Polmar S, Saxon A, Rohr
A, Yang W, Drouin M.
Aspartame is no more likely than placebo to cause uticaria/angioedema:
Results of a multi-center, randomized, double-blind, placebo-controlled
crossover study.
J Allergy Clin Immunol. 1993: 92;513-520.
[  Typically, this industry funded study manages to avoid the deadly words,
"formaldehyde" and "formic acid", the most potent allergens produced in the body
from the 11% methanol component of aspartame.  It is surely fruitless to attempt
to study allergies while ignoring the most potent allergens. ]

87. Food and Drug Administration.
Food additives permitted for direct addition to food for human consumption:
Aspartame.
1984; 49: 6672-6677.

88. Food and Drug Administration.
Food additives permitted for direct addition to food for human consumption:
Aspartame.
1996; 61(126)(21CFR Part 172): 33654-33656.

89. Scientific Committeee on Food.
Opinion of the Scientific Committee on Food:
Update on the Safety of Aspartame.
Brussels: European Commission; Deacember 2 2002. SCF/CS/ADD/EDUL/222 Final.
************************************************************

[ Geha et al. (1993)  used monocrystalline cellulose in gelatin capsules as
their placebo.   A  recent study suggests that an inhaled cellulose powder
extract may prevent classic hay fever attacks.
Another study  find hypersensitivity reactions in patients [ blood ]
dialysed with cellulose or synthetic membranes".
There are scores of studies on gelatin allergy.

Adv Ther. 2003 Jul-Aug; 20(4): 213-9.
Use of cellulose powder for the treatment of seasonal allergic rhinitis.
Josling P, Steadman S.
Herbal Health Centre, Battle, UK.

This study was designed to determine whether a unique cellulose powder
extract could prevent the classic hay fever attack from occurring among
volunteers who have suffered for some years.
Nasaleze enhances nasal mucus, which allows the filtration of allergens, to
ensure that only clean air reaches the lungs.
One hundred two volunteers were recruited and, using a simple 5-point
scoring system to grade their general well-being and severity of any hay
fever attacks, the overall average score was 3.85, indicating that Nasaleze
was able to control hay fever very well.
Rapid relief of symptoms was also demonstrated, sometimes within minutes
after inhalation.
Overall, 77% of volunteers reported a significant reduction in the number of
challenges throughout the study period and most graded Nasaleze as more
effective and reported fewer side effects than with a wide range of chemical
treatments.  Publication Types:  Clinical Trial  PMID: 14669817

Nephrologie. 1996; 17(3): 163-70.
[Risk factors for acute hypersensitivity reactions in hemodialysis]
[Article in French]
Simon P, Potier J, Thebaud HE.
CH La Beauchee, St-Brieux.

The aim of this prospective study was to evaluate the prevalence of
anaphylactoid reactions (AR) in patients dialysed with cellulose or
synthetic membranes and the possible link with ACE inhibitors....
PMID: 9064565

Biologicals. 2003 Dec; 31(4): 245-9.
Removal of gelatin from live vaccines and DTaP-an ultimate solution for
vaccine-related gelatin allergy.
Kuno-Sakai H, Kimura M.
Department of Public Health and Social Medicine, School of Medicine, Tokai
University, 143 Shimokasuya, Isehara City, Kanagawa, 259-1193, Japan.

From the early 1990s infants started to receive acellular pertussis vaccine
combined with diphtheria and tetanus toxoids (DTaP) before live vaccines
such as measles, rubella, and mumps vaccines, which contained gelatin as a
stabilizer. Then, an increasing number of cases of anaphylactic/allergic
reactions to those live vaccines were reported. Almost all these cases had a
previous history of receiving three or four doses of DTaP containing
gelatin.Anaphylactic/allergic reactions to live measles vaccine were
analyzed using information obtained from the Reporting System, a
retrospective study, as well as from the Monitoring System, a prospective
study. Dramatic decreases in anaphylactic/allergic reactions to live measles
vaccines were observed immediately after each manufacturer marketed
gelatin-free or gelatin (hypo-allergic)-containing live measles vaccine, and
since the end of 1998 reports on anaphylactic/allergic reactions to live
measles vaccine have almost ceased.  PMID: 14624794

Clin Exp Allergy 2000 May; 30(5): 739-43.
Why do some dietary migraine patients claim they get headaches from
placebos?
Strong FC 3rd
Departamento de Ciencia de Alimentos
Faculdade de Engenharia de Alimentos
Universidade Estadual de Campinas, SP, Brasil
http://www.unicamp.br/unicamp/universidade/universidade.html
and Department of Chemistry, Bucknell University
www.bucknell.edu  570-577-2000   Lewisburg, PA, USA.
Strong Frederick C   fstrong@...
c/o C H Clapp Chemistry Dept, Graduate/Special, guest

BACKGROUND: In six double-blind studies involving 182 tests of dietary
migraine patients sensitive to tyramine and beta-phenylethylamine, 18%
reported headaches from placebos which were all concealed in gelatin
capsules. OBJECTIVE: The purpose of this research was to test a hypothesis:
gelatin is partially hydrolysed animal protein;
(partially) hydrolysed vegetable protein (PHVP) is known to cause migraine;
perhaps the gelatin caused some of the headaches.
METHOD: The author tested this hypothesis on himself because he suffers from
dietary migraine.
He proved this in a double-blind test with tyramine hydrochloride (TYH).
The amount required for the test was so small (1 mg) that it was tasteless
and capsules were unnecessary.
The author then undertook tests with a capsule, PHVP, monosodium glutamate
(MSG) aspartame (a dipeptide) and TYH, adjusting quantities to give a
moderate headache.
Samples were mixed with foods to simulate normal eating: the capsule with
potato chips, aspartame with orange juice and the rest with cottage cheese
or ricotta cheese.
Times were measured from ingestion (1) to start of the headache and (2) to
maximum headache intensity.
Each experiment was repeated three times.
The headaches were relieved with caffeine.
RESULTS: Of eight double-blind test samples, the author identified correctly
the two placebos and five of the six samples containing tyramine.
Quantities giving moderate headaches were: 1 gelatin capsule, 400 mg MSG,
118 mg PHVP, 4.0 mg aspartame and 1.0 mg TYH.
Typical times for the three repetitions of the two time periods were 8, 9
and 11 and 17, 19 and 22 min.
CONCLUSIONS: Capsules may give headaches to dietary migraine patients that
are similar to those from foods.
This would explain some of the headaches of patients from placebos.
The double-blind test and the repeatability of the time measurements
demonstrated the validity of the experiments.  PMID: 10792367   ]

J Allergy Clin Immunol. 1995 Feb;  95(2):  639-640.
Aspartame-induced hives.
Anthony Kulczycki, Jr., MD   akulczyc@...
Assc. Prof. of Medicine
Division of Allergy and Immunology, Department of Medicine
Washington University School of Medicine
Box 8122, 660 South Euclid Avenue, St. Louis, MO 63110.

Correspondence:
To the Editor:

The failure by Geha et al. (J Allergy Clin Immunol 1993;  92: 513-20) to
find more than two subjects with aspartame-induced hives may have resulted
from flaws in study design.
After reviewing their study protocol in 1986 to 1987, I declined to take
part because I identified the defects numbered below.

My perspective is based on my own additional experience with
aspartame-induced hives, summarized as follows.

During 1986, after reporting two index cases (1), I was contacted by 88
individuals in the St. Louis area who had heard a direct televised appeal
for subjects and had suspected that their chronic urticaria or angioedema
might be due to aspartame.
By contrast, indirect attempts to recruit subjects (i.e., appeals to local
allergists) yielded no referrals during the same period.
Few of my telephone respondents had consulted an allergist.

Seventy-five of the individuals who telephoned were willing to avoid
aspartame for 2 weeks;
50 experienced complete resolution of hives upon aspartame avoidance;
22 were willing to openly rechallenge themselves with aspartame, and
each re-experienced allergic skin reactions.
With resources to study only six of these individuals, I found four of them
(all women) who experienced hives after double-blind, placebo-controlled
challenges with aspartame.
One subject (age 40) had a reaction 3 hours after challenge, which was
similar to the initial cases (1);
one subject (age 26) had an immediate reaction and a delayed reaction 12
hours after challenge;
one subject (age 29) had an "immediate reaction" 2.5 hours after challenge
and subsequent delay outbreaks of hives at 9, 23, 30, and 43 hours, which
required treatment; and
one subject (age 43) had only a delayed reaction at 22 hours after
challenge;
no subjects reacted to placebo.
Thus it should not be surprising that the subjects B01 and F03 in the study
by Geha et al. experienced delayed reactions to aspartame.
Allergists need to recognize that aspartame-induced hives can be acute,
delayed, or chronic.  [ As in the case of morning-after hangovers from the
formaldehyde produced from the methanol impuritities in wines and dark
liquors, it takes some hours for the liver to process the aspartame-derived
methanol into formaldehyde and formic acid.

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4  ]

The defects I identified in the study by Geha et al. are the following:

1. Subject recruitment methods.

There are two types of recruiting:
direct appeals to subjects and  indirect appeals through physicians.
Indirect recruiting is less successful when subjects rarely visit physicians
and when physicians are not actively looking for a given disorder.
Geha et al. relied primarily on indirect types of recruiting and garnered
only 86 referrals.
I found that direct appeals to patients via television were essential for
adequate recruitment of aspartame-allergic subjects.
From my perspective, the recruiting efforts of Geha et al were inadequate to
address the problem of aspartame-induced hives, and therefore their
conclusion that "the incidence (of aspartame-induced urticaria) is "rare" is
unwarranted.

There remains no study that adequately defines the incidence of
aspartame-induced hives in the population. [ Indeed, the Geha study is
widely used by the aspartame industry to deny the validity of hundreds of
cases of allergic and
dermatological reactions,  disparaging dismissed as "anecdotal reports". ]

2. Convenience, compensation, and safety for subjects.

Geha et al. note that 32 of the individuals contacted "decline to
participate".  Their study design probably tended to discourage the
participation of the subjects who were most likely to be allergic to
aspartame.
Why?
The more a potential subject finds that aspartame consumption correlates
with hives, the less motivation the potential subject has to learn about the
cause of his or her hives and to participate in an inconvenient, 5-day
hospital stay, especially if compensation is inadequate.
The more uncertain the correlation, the more likely a potential subject
might be to welcome an extensive evaluation.
(The authors should disclose the financial compensation to subjects;
it may have been inadequate to encourage sufficient subject participation.)
Also, subjects with more severe or delayed symptoms would be more likely to
decline to participate because of the potential for a severe reaction.
Having once experienced that one diet soda could produce severe or delayed
allergic reactions, some of the potential subjects most sensitive to
aspartame may have been unwilling to participate out of concern for their
safety.
(The study required ingestion of the equivalent of over six cans of diet
soda.)
Obviously, the nine enrolled subjects in the study by Geha et al who had
required no medications did not have severe urticaria or angioedema.

My challenge procedures were more conveniently designed.
They involved two 4-hour outpatient visits, usually on Saturdays, with 50 mg
of aspartame.  [ 2 oz diet soda equivalent ]
The six subjects that I found to have positive responses to aspartame were
unwilling to be referred to the Geha et al. study because they believed it
would be too inconvenient and possibly unsafe.

Thus several aspects of the Geha et al. study design may have contributed to
selectively discourage the participation of the subjects likely to be
allergic to aspartame.

3. Inclusion or exclusion criteria and challenge design.

Avoiding "confounding (but unspecified) medication within three weeks" is
not adequate preparation for aspartame challenges.
The national task force recommendation to avoid astemizole for at least 6
weeks, and also tricyclic antidepressants, before skin testing (2) should
clearly apply to this type of challenge study.
Because astemizole, which can suppress responses to skin tests (and
presumably challenges) for possibly up to 12 weeks, has been commonly used
in treatment of chronic urticaria, prior astemizole use might explain some
of the negative aspartame challenge results.
Withdrawal from the astemizole might account for one or both of the
"positive" placebo challenge results.
I ask the authors, "How many subjects had taken astemizole during the 12
weeks before their challenges?"
(Also, what justifies the authors' apparent assumption that "a positive
histamine skin test" will guarantee a positive challenge?)

Although five subjects in the "population identified as alleged responders"
by Geha et al. had food-induced hives and seven subjects had allergic
respiratory problems, apparently no effort was made to limit the subjects'
diets or to exclude other recognized causes of chronic urticaria (3).

Because of these deficiences in study design, I am concedrned that the
NutraSweet Company-sponsored study by Geha et al. does not accurately
reflect the incidence of aspartame-induced hives.
I hope that, from among the dozens of allergist who have cases of
aspartame-induced hives, additional studies will be forthcoming.

Anthony Kulczycki, Jr, MD

References:

1. Kulczycki A.
Aspartame-induced urticaria.
Ann Intern Med. 1986; 104: 207-208.

2. Bernstein IL.
Proceedings of the Task Force on guidelines for standardizing old and new
technologies used for the diagnosis and treatment of allergic diseases.
J Allergy Clin Immnol. 1988; 82: 494.

3. Kulczycki A, Atkinson JP.
Urticaria and angioedema.
In: Korenblat PE, Wedner HJ, eds. Allergy: theory and practice. 2 ed.
Philadelphia: WB Saunders Co., 1992, 217-228.
*************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 3.30.4 rmforall   [ 150 KB ]

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

[ Comments by Rich Murray are in square brackets.  To increase the
readability of the dense, specialized, condensed text of a brief scientific
letter (usually not peer reviewed), I have added spacing without altering
text, while correcting minor typos.

I then offer some critical analyses and extensions of the references, since
the relevant scientific literature is contaminated by long-term, systematic
influence by corporate vested interests. ]

"A 60-year-old Caucasian woman presented with a 6-month history of eyelid
dermatitis...

By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.

Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.

She had begun using an aspartame-based artificial sweetener 5 months prior
to the onset of her dermatitis. [ 12 months of low-level aspartame use until
stopping. ]

Within 1 week of discontinuing the aspartame, her eyelid dermatitis resolved
completely and has not recurred over 18 months without specific
treatment....

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied."

[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet
soda gives 200 mg aspartame.  An aspartame reactor can have immediate strong
symptoms from an under-the-tongue wafer with 4 mg aspartame.
(Appendix A, for comments, abstracts, and links.) ]

Contact Dermatitis. 2003 Nov; 49(5): 258-9.
Systemic contact dermatitis of the eyelids caused by formaldehyde derived
from aspartame?
Hill AM, Belsito DV.   DBelsito@...
Division of Dermatology, University of Kansas Medical Center, 3901 Rainbow
Blvd., Kansas City, KS 66160, USA.     PMID: 14996049

A. Michele Hill and Donald V. Belsito
Division of Dermatology, University of Kansas Medical Center
3901 Rainbow Blvd., Kansas City, KS 66160, USA  [ (Appendix B, for more
abstracts by Donald V. Belsito, selections, and institutions) ]

Key Words: allergic contact dermatitis; aspartame; eyelids; formaldehyde;
systemic contact dermatitis.

Formaldehyde is a common and ubiquitous contact allergen.
Sources of exposure include hair and skin care products, cosmetics, topical
medications, permanent press clothing, cleaning agents, disinfectants, paper
and even smoke. [ Also, new buildings, mobile homes,  furniture, carpets,
drapes, particleboard,  medical facilities, methanol, aspartame, dimethyl
dicarbonate, dark wines and liquors   ]

Sensitization is reported in between 2.2 and 9.6% of patients patch tested
(1,2).
[ (Appendix C, for abstracts on rates of formaldehyde sensitivity in control
groups, as a possible first estimate of the impact of widespread exposure to
aspartame since 1981.) ]

Case Report

A 60-year-old Caucasian woman presented with a 6-month history of eyelid
dermatitis.
A corticosteroid-containing opthalmologic ointment improved but did not
clear the rash.
She failed to improve when she discontinued the use of all eyelid cosmetics
and nail polishes for 2 months.
She had had a facial dermatitis in 1995, for which she had been patch tested
and found to be allergic to formaldehyde, quaternium-15 and fragrances.
She had also had incidental, non-relevant reactions to neomycin and
ethylenediamine.
Her dermatitis had resolved with a change to formaldehyde-, quaternium-15
and fragrance-free facial and nail cosmetics.

There was no personal or family history of atopy or psoriasis.
Her only oral medication was celecoxib that she had taken for years prior to
the onset of her blepharitis.
She had also taken multivitamins, calcium and flaxseed oil for many years.
She worked as a homemaker and library volunteer. [ It is relevant as to
whether she had the standard urban diet with high protein and animal fats,
meats, milk products, some  inorganic fruits and vegetables, high sugars,
and processed foods.  Mercury dental amalgams and mercury contaminated fish
could also play a role.  Was her water fluoridated or otherwise
contaminated?  Were there toxic mold exposures in her environment?  Was she
exposed to pesticides in her area?  ]

Her eyelid dermatitis was kept clear with tacrolimus 0.03% ointment X2
daily.
She underwent patch testing to the North American Contact Dermatitis Group
standard tray, the University of Kansas' supplemental standard tray, and to
her cosmetics, cleansers, skin and hair care products and topical
medications.
She had relevant positive reactions at days 2 and 4 to formaldehyde (++),
quaternium-15 (++), diazolidinyl urea (+), DMDM hydantoin (+) and
imidazolidinyl urea (++), her hair care products and cleansers containing
multiple sources of these allergens.

She was extensively instructed in avoidance of formaldehyde and formaldehyde
releasers, as well as that of her multiple, currently non-relevant
allergens, including fragrance, benzalkonium chloride, neomycin, bacitracin,
p-phenylenediamine and black rubber mix.   [ As a medical layman, I'm
disturbed to see all these chemicals that I know nothing about. ]

By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.

Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.

She had begun using an aspartame-based artificial sweetener 5 months prior
to the onset of her dermatitis. [ 12 months of low-level aspartame use until
stopping. Aspartame reactors discover this possibiliy usually from the Net,
alternative medicine providers, media, nurses, friends, and pharmacists,
rarely from physicians. ]

Within 1 week of discontinuing the aspartame, her eyelid dermatitis resolved
completely and has not recurred over 18 months without specific treatment.
[ This quick healing response is typical of cases of low-level use with few
symptoms.  Long-term heavy users , above 2 L, about 6 12-oz cans daily for
years, often have severe craving and withdrawal symptoms for weeks, with
gradual recovery for months.  H. J. Roberts, MD has summarized over 1200
cases.  (Appendix H)   Three recent case reports are added here.
(Appendix I) ]

Unfortunately, she refused to undergo rechallenge with the sweetener.
[  This is usually the case.   Commonly, there is inadvertent reexposure,
with immediate painful symptoms, even with low doses. ]

Discussion

The artificical sweetener, aspartame, is consumed by 54% of adults in the
USA (3).

It has been reported to cause dry eyes and difficulty in wearing contact
lenses (3) but never allergic contact dermatitis. [ Reference (3)  is given
in full  here. (Appendix H)   Roberts H J.  Dry eyes from use of aspartame
(Nutrasweet):  Associated insights concerning the Sjogren syndrome.
The Townsend Letter for Doctors, January 1994.   Appendix H also quotes
several cases of eyelid dermatitis from his review of 1200 cases in
Aspartame Disease: An Ignored Epidemic (2001). ]

Aspartame, an L-aspartyl-L-phynylalanine methyl ester, is hydrolysed in the
intestine to phenylalanine (50%), aspartic acid (40%) and aspartaic acid
methyl ester (10%).

The methyl ester is then converted to methyl alcohol (methanol) and carried
by the portal vein to the liver.

Methanol is there oxidized to formaldehyde that is converted into formic
acid (formate) by alcohol dehydrogenase, aldehyde dehydrogenase and the
microsomal oxidase pathway.

This occurs not only in the liver, but also in other organs containing high
levels of these enzymes, including the eye (4,5).

Formaldehyde binds proteins and nucleic acids, forming adducts difficult to
eliminate via metabolism.

Trocho et al. (6) demonstrated the formation of formaldehyde adducts with
DNA and proteins after administration of 20 mg/kg 14C-labelled aspartame to
rats, concluding that these adducts were responsible for functional
alterations of proteins and for DNA mutations leading to autoimmunity, cell
death or malignant transformation.  [ (Appendix E) gives links, comments,
and quotes for the debate on the key Trocho study. ]

In contrast to Trocho et al. (6), McMartin et al. (7) studied formaldehyde
levels after large doses (3,000 mg/kg) of 14C-labelled methanol and
14C-labelled formaldehyde in monkeys, which unlike rats are sensitive to the
toxicities of methanol.

No increased formaldehyde derived from methanol was found.

High levels of formic acid were found in all monkeys that were given
methanol or formaldehyde.

[ (Appendix F) reviews the major studies.  Oppermann et al (1973, 1976)
found that 30% of the methanol from aspartame fed to monkeys remained in
body tissues, indubitably as toxic products of formaldehyde and formic acid.
They did not test methanol product  retention in humans.  McMartin et al
(1979) reported significant formaldehyde retention in the midbrain of one
monkey from oral aspartame, and substantial formic acid in liver, kidney,
optic nerve, cerebrum, and midbrain in two other monkeys.  It is clear that
his formaldehyde assays were too insensitive to give valid measurements.
There has been a dearth of relevant primate and human studies ever since. ]

Based on the work of McMartin and al. (7), Tephly (8) concluded that the
radioactive carbon from methanol, which was found in DNA and protein by
Trocho et al., was due to the normal physiologic flow of single-carbon units
through the folate pathway.

Stegink et al. (9) have shown that doses of 100 mg/kg or greater of
aspartame are required to increase methanol blood levels (and thus,
presumable formaldehyde formic acid levels) above control.

This would be equivalent to consuming 35 cans of diet beverage at one
sitting for a 70 kg person.  [ This is a typical aspartame industry PR ploy,
well designed to plant the impression that only absurdly huge amounts of
diet soda might supply damaging amounts of methanol-derived formaldehyde and
formic acid toxic residuals in body tissues, thus reducing methanol blood
levels.  So, it is a classic red herring tactic to focus on methanol blood
levels.  It is urgent to determine the actual accumulation from long-term
exposure to aspartame of toxic products of formaldehyde and formic acid in
many specific tissues in vulnerable groups of people, especially long-term
heavy users, above 6 12-oz cans diet soda (about 2 L) daily for years, who
have the typical suite of serious symptoms. ]

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12 mg
daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

[ http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall ]

This long-term low-level chronic toxic exposure leads to typical patterns of
increasingly severe complex symptoms, starting with headache, fatigue, joint
pain, irritability, memory loss, and leading to vision and eye problems, and
even seizures. In many cases there is addiction.  Probably there are immune
system disorders, with a hypersensitivity to these toxins and other
chemicals.  (Appendixes D, E, F, G, H, I, J) ]

Leon et al. (10) studied doses of 75 mg/kg of aspartame daily for 24 weeks
and found no change in blood or urine methanol levels and no symptoms of
methanol toxicity.

The dose used in Leon's study is 25 times the 90th percentile daily
consumption of aspartame (11). [ Appendix E gives an abstract by Davoli
(1986), using a properly sensitive assay,  that proved a temporary rise in
blood methanol levels in humans from a single aspartame dose.  Trocho
pointed out that formaldehyde adducts are persistent and thus cumulative. It
is reasonable to state that with long-term chronic formaldehyde exposure, it
may take a long time to both accumulate adducts and develop markedly
increased sensitivity and a series of complex symptoms .  Adequate studies
would have to test substantial exposures over a year or longer with large
numbers of vulnerable types of people and record all symptoms. ]

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied.
[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet
soda gives 200 mg aspartame.  An aspartame reactor can have immediate strong
symtoms from an under-the-tongue wafer with 4 mg aspartame.  (Appendix A,
for comments, abstracts, and links.) ]

However, it is possible that the eye, with its high level of metabolic
activity, could be affected by methanol (and subsequently formaldehyde)
released from these low levels of aspartame and respond as a localized
target organ to minute amounts of her known allergen, formaldehyde, or its
metabolite, formate.

It is also possible that the amplifying effects of cell-mediated immunity
might detect trace amounts of a chemical not identified by more standard
assays, such as blood or urine levels. [ (Appendix D gives Thrasher's data
about immune system reactions from long-term, low-level formaldehyde
exposure, while Martin Pall gives a complex general theory, specifically
discussing formaldehyde as a major trigger.)

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame: Martin L. Pall: Murray:
12.9.2 rmforall

FASEB J 2002 Sep; 16(11): 1407-17.
NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and
organic solvents as the mechanism of chemical sensitivity in multiple
chemical sensitivity.
Pall ML.    PMID: 12205032    [ 162 references, received 1.3.2 ]
School of Molecular Biosciences, Washington State University,
Pullman, Washington 99164-4660, USA.   martin_pall@... ]

Such a hypothesis might explain why her dermatitis was limited to the
eyelids and give clinical support to Trocho's theory of formaldehyde
adducts.

Unfortunately, without rechallenging her with aspartame, we cannot test this
hypothesis.

Nonetheless, her long-lasting remission following discontinuation of
aspartame intake suggests that its breakdown to formaldehyde may have been a
possible mechanism for her prior blepharitis.

References

1. Christophersen J, Menne' T, Tanghoj P, Andersen K E, Brandrup F.
Clinical patch test data evaluated by multivariate analysis.
Contact Dermatitis 1989: 21: 291-299.

2. Fransway AF, Schmitz N A.
The problem of preservation in the 1990s.
II. Formaldehyde and formaldehyde-releasing biocides: incidences of
cross-reactivity and the significance of the positive response to
formaldehyde.
Am J Contact Dermat. 1991: 2: 78-88.

3. Roberts H J. Dry eyes from use of aspatame (Nutrasweet):
Associated insights concerning the Sjogren syndrome.
The Townsend Letter for Doctors, January 1994. [ full text in Appendix H ]

4. Murray T G, Burton T C, Rajani C, Lewandowski M F,
Burke J M, Eells J T.
Methanol poisoning: A rodent model with structural and functional evidence
for reinal involvement.
Arch Opthalmol 1991: 109: 1012-1016.

5. Eells J T.
Methanol-induced visual toxicity in the rat.
J. Pharmacol Exp Ther 1991: 257: 56-63.

6. Trocho C., Pardo R, Fafecas I, Virgili J, Remesar X,
Fernandez-Lopez, J A.
Formaldehyde derived from dietary aspartame binds to tissue components in
vivo.
Life Sci 1998 1988: 63: 337-349. [ abstract and quotes in Appendix E )

7. McMartin K E, Mrtin-Amat G, Noker P E, Tephly T R.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Biochem Pharmacol 1979: 28: 645-649. [ abstract, quotes, discussion, related
studies in Appendix F ]

8. Tephly T R: Comments on the purported generation of formaldehyde from
the sweetener aspartame.
Life Sci 1999: 65: 157-160.   [ letter, usually not peer-reviewed,
abstract in Appendix E  ]

9. Stegink L D, Brummel M C, McMartin-Amat G., Filer L J, Baker G L,
Tephly T R.
Blood methanol concentrations in normal adult subjects administered abuse
doses of aspatame.
J Toxicol Environ Health 1981: 7: 281-290.

10. Leon A S, Hunninghake D B, Bell C, Rassin D K, Tephly T R.
Safety of long-term large doses of aspartame.
Arch Intern Med 1989: 149: 2318-2324.

11. Tschanz C., Butachko H, Stargel W, Kotsonis F N (eds).
The Clinical Evaluation of a Food Additive: Assessment of Aspartame
Boca Raton: CRC Press, 1996.
************************************************************

Appendix A:

http://groups.yahoo.com/group/aspartameNM/message/846
aspartame in Merck Maxalt-MLT worsens migraine,
AstraZeneca Zomig, Eli Lilly Zyprexa,
J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab,
Pfizer Cool Mint Listerine Pocketpaks: Murray 7.16.2 rmforall

Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB  Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology   newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research   RLipton@...

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall

Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches. Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA.   neurotulsa@...
Aspartame, a popular dietetic sweetener, may provoke headache in some
susceptible individuals. Herein, we describe three cases of young women
with migraine who reported their headaches could be provoked by chewing
gum sweetened with aspartame. [ 6-8 mg aspartame per stick chewing gum ]

http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 1.17.2 rmforall

Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following Discontinuation of Dietary
Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is
often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome
for two to 17 years are described.
All had undergone multiple treatment modalities with limited success.
All had complete, or nearly complete, resolution of their symptoms within
months after eliminating monosodium glutamate (MSG) or MSG plus aspartame
from their diet.
All patients were women with multiple comorbidities prior to elimination of
MSG.
All have had recurrence of symptoms whenever MSG is ingested.
PMID: 11408989

Siegfried O. Schmidt, MD  Asst. Clinical Prof.  siggy@...
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
352-376-5071

Several recent pro-aspartame reviews simply ignore these reports by eminent
mainstream researchers, as well as the tidal surge of complaints by users.

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall  EU Scientific Committee on Food, a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame (12.4.2): 59 pages, 230 references

J Am Diet Assoc. 2004 Feb; 104(2): 255-75.
Position of the American Dietetic Association: use of nutritive and
nonnutritive sweeteners.
American Dietetic Association.    PMID: 14760578

http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review by American Dietetic Association Feb 2004:
Murray 4.1.4 rmforall

"Survey of aspartame studies: correlation of outcome and funding sources,"
1998, unpublished:   http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed medical
literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100%) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91%)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown,
OH 44501    330-740-3621    rwalton193@...
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

http://groups.yahoo.com/group/aspartame/messages 770 members 16,692 posts  ]
************************************************************

research on aspartame (methanol, formaldehyde) toxicity:
Murray 4.1.4 rmforall

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 3.30.4 rmforall   [ 150 KB ]

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1065
politicians and celebrities hooked on diet sodas (aspartame):
Murray 3.24.4 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 751 aspartame items.

http://groups.yahoo.com/group/aspartameNM/messages
for 1068 posts in a public searchable archive  120 members

http://groups.yahoo.com/group/aspartame/messages 777 with 16,703 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
( becomes formaldehyde in body ):  EU Scientific Committee on Foods 7.12.1:
Murray 1.22.4 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.  toxicology@...
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1055
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 3.11.4

http://groups.yahoo.com/group/aspartameNM/message/1056
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/946
Functional Therapeutics in Neurodegenerative Disease Part 1/2:
Perlmutter 7.15.99: Murray 1.10.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/97
Lancet website aspartame letter 7.29.99:
Excitotoxins 1999 Part 1/3 Blaylock: Murray 1.14.0 rmforall
The Medical Sentinel Journal  1999 Fall; (95 references)
http://www.dorway.com/blayenn.html
aspartame (methanol, formaldehyde) toxicity: Murray 1.1.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1034
Brain cell damage from amino acid isolates (aspartame releases
phenylalanine, aspartate, methanol [formaldehyde, formic acid]  Bowen &
Evangelista May 6 2002: Murray 11.10.3 rmforall

http://www.aspartame.ca/Brain%20Cell%20Damage.pdf
Brain cell damage from amino acid isolates 5.6.2   41 references
detailed 22 page review by James D. Bowen, MD and Arthur M. Evangelista,
former FDA Investigator  orwilly@...

http://groups.yahoo.com/group/aspartameNM/message/628
Rich Murray: Professional House Doctors: Singer:  EPA: CPSC:
formaldehyde toxicity 6.10.1 rmforall

http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 1.17.2 rmforall
Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is
often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome
for two to 17 years are described.
All had undergone multiple treatment
modalities with limited success. All had complete, or nearly complete,
resolution of their symptoms within months after eliminating monosodium
glutamate (MSG) or MSG plus aspartame from their diet.
All patients were women with multiple comorbidities
prior to elimination of MSG.
All have had recurrence of symptoms whenever MSG is ingested.

Siegfried O. Schmidt, MD  Asst. Clinical Prof.  siggy@...
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
352-376-5071

Debbie J. Hypes   painfreeliving@...  304-872-4141  (Case # 1 of 4)
P.O Box 25  Lookout, WV 25868-0025  She has about 1,000 on her local
mailing list, and has been a volunteer activist since 1997.  Her guide
first came out in 1997:  http://www.Pain-Free-Living.net
"The Food Plan: How To Do It"  $ 5 by mail,  free by email.
Her sister Darlene, now 47,  cured her own severe fibromyalgia in 1995
by using an elimination diet, and then Debbie also cured herself by
1997.  Their doctor, Siegfried Schmidt, paying attention, tried it on
two more patients, who got well, and are his third and fourth cases.

http://groups.yahoo.com/group/aspartameNM/message/846
RTM: aspartame in Merck Maxalt-MLT worsens migraine,
AstraZeneca Zomig, Eli Lilly Zyprexa,
J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab,
Pfizer Cool Mint Listerine Pocketpaks 7.16.2 rmforall
Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB  Headache 2001 Oct; 41(9): 899-901.
[Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg.]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology   newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research   RLipton@...

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches.
Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA.   neurotulsa@...
Aspartame, a popular dietetic sweetener, may provoke headache in some
susceptible individuals. Herein, we describe three cases of young women
with migraine who reported their headaches could be provoked by chewing
gum sweetened with aspartame. [6-8 mg aspartame per stick chewing gum]

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M  ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo.  Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male)  alemany@...

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ].  Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@...    919-684-3303, 660-5657
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall ]

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity 6.4.1 rmforall   four double-blind studies

http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers:
aspartame toxicity 6.4.1 rmforall    two double-blind studies

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame (12.4.2): 59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall  EU Scientific Committee on Food, a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1018
aspartame toxicity coverup increases danger of corporate meltdown:
Michael C. Carakostas of Coca-Cola: Murray 8.11.3 rmforall
http://www.isrtp.org/new_members/members1.htm
The International Society of Regulatory Toxicology and Pharmacology
Carakostas, Michael C., DVM, PhD Director/Scientific & Regulatory
Affairs   The Coca-Cola Company PO Drawer 1734 Atlanta, GA 30301
T. 404/676-4234   F. 404/676-7166   E-mail: mcarakostas@...
http://www2.coca-cola.com/ourcompany/columns_aspartame.html  [photo]
Aspartame: The world agrees it's safe   By Michael Carakostas, DVM, PhD
Director, Scientific and Regulatory Affairs, Coca-Cola

It is commendable that Carakostas mentions the core problem, albeit
disparagingly:   "During digestion, aspartame yields a very small amount
of methanol-- as do many other food substances. The body converts this
methanol to formaldehyde, which is instantly converted to formate.
Formate is quickly eliminated as carbon dioxide and water."

Plenty of evidence in the mainstream scientific literature since 1973
shows that as much as 30% of the formaldehyde is retained in the body as
toxic, cumulative adducts to the DNA, RNA, and proteins in all cells and
tissues, leading to pointed reports by informed doctors and experts.
Clearly, there are no safe levels for chronic, low-level formaldehyde
exposure.  If just 10% of the methanol from six cans of diet soda is
retained in the body as toxic products of formaldehyde and formic acid,
that is sixty times the EPA limit for allowable formaldehyde from daily
drinking water.

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Formaldehyde was administered for 104 weeks in drinking water supplied
ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
rats beginning at six weeks of age at concentrations of 2,500, 1,500,
500, 250, 50, or 0 mg/L.
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase in total
malignant tumors in the treated groups and showed specific carcinogenic
effects on various organs and tissues.  PMID: 12562630

Surely the authors deliberately emphasized that aspartame is well-known
to be a source of formaldehyde, which is an extremely potent, cumulative
toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested
aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No.      No. of Bioassays  Species    No.       Route of Exposure
108.  "Coca-Cola"     4     Rat       1,999    Ingestion, Transplantal Route
109.  "Pepsi-Cola"    1      Rat          400         Ingestion
110.   Sucrose          1      Rat          400         Ingestion
111.   Caffeine          1      Rat          800         Ingestion
112.   Aspartame      1      Rat       1,800         Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]

http://www.dorway.com/tldaddic.html  5-page review
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter  2000 Jan;  HJRobertsMD@...
http://www.sunsentpress.com/    sunsentpress@...
Sunshine Sentinel Press  P.O.Box 17799  West Palm Beach, FL 33416
800-814-9800 561-588-7628 561-547-8008 fax

http://groups.yahoo.com/group/aspartameNM/message/669
1038-page medical text   "Aspartame Disease: An Ignored Epidemic"
published May 30  2001    $ 60.00 postpaid    data from 1200 cases
available at  http://www.amazon.com
over 600 references from standard medical research

http://www.dorway.com  David O. Rietz  over 12,000 print pages
Mission-Possible-USA    Betty Martini   770-242-2599
Bettym19@...     dorietz@...
http://www.dorway.com/asprlink.html   many links
http://www.dorway.com/nslawsuit.txt    Jeff Martin, Attorney
http://www.dorway.com/doctors.txt
What many informed doctors are saying/have said about aspartame

http://www.HolisticMed.com/aspartame    603-225-2100
Aspartame Toxicity Information Center    Mark D. Gold
mgold@...    12 East Side Drive #2-18 Concord, NH 03301
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

Aspartame Consumer Safety Network and Pilot Hotline  [1987-2001]
Mary Nash Stoddard, Founder & President
P.O. Box 780634  Dallas, TX 75378   .
214-352-4268   marystod@...
http://web2.airmail.net/marystod/index.html
http://web2.airmail.net/marystod/espanol.htm
Toxicology Sourcebook: "Deadly Deception: Story of Aspartame"

http://groups.yahoo.com/group/aspartameNM/message/802
RTM: 700.club.com: CBN:
Totheroh & Robertson: aspartame expose 2.13.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/805
RTM: Ive: UK Daily Mirror Magazine: aspartame toxicity 2.18.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research 7.31.2 rmforall

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 7.10.0 rmforall

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9: rmforall

http://groups.yahoo.com/group/aspartameNM/message/927
Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall  EU Scientific Committee on Food

http://groups.yahoo.com/group/aspartameNM/message/841
RTM: Merisant Co., MSD Capital, Dell Computer Corp., NutraSweet Co.,
JW Childs Assc.: aspartame-neotame toxicity 7.10.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/876
hyperthyroidism (Graves disease) in George and Barbara Bush, 1991--
aspartame toxicity?  Roberts 1997: Murray 10.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/874
re "dry drunk": Bisbort: danger to President Bush from aspartame
toxicity: Murray: 2.24.2  9.29.2 rmforall

Many scientific studies and case histories report:  * headaches
* many body and joint pains (or burning, tingling, tremors, twitching,
spasms, cramps, stiffness, numbness, difficulty swallowing)
*  fever, fatigue, swollen glands  * "mind fog", "feel unreal", poor
memory, confusion, anxiety, irritability, depression, mania, insomnia,
dizziness, slurred speech, sexual problems,  poor vision, hearing
(deafness, tinnitus), or taste  * red face, itching, rashes, hair loss,
burning eyes or throat, dry eyes or mouth, mouth sores, burning tongue
* obesity, bloating, edema, anorexia, poor appetite or excessive hunger
or thirst    * breathing problems, shortness of breath * nausea,
diarrhea or constipation  * coldness  * sweating  * racing heart, low or
high blood pressure, erratic blood sugar levels  * hypothryroidism or
hyperthyroidism  * seizures  * birth defects  * brain cancers
* addiction  * aggrivates diabetes, autism, allergies, lupus, ADHD,
fibromyalgia, chronic fatigue syndrome, multiple chemical sensitivity,
multiple sclerosis, and interstitial cystitis (bladder pain).
***********************************************************

http://www.readthelabel.org.uk/  Additives Survivors' Network (UK)
Geoff Brewer <geoffbrewer@...>
http://www.chem.ox.ac.uk/mom/aspartame/aspartame.html
http://www.chm.bris.ac.uk/webprojects2000/srogers/sarah.html
Sarah Rogers <sr8442@...>
http://www.react.ie/Health/Nutrition/Aspartame.htm Ireland
http://members.tripod.com/~mission_possible/scotland_branch.html
http://www.aspartame.ca/indexa.html John T. Linnell <admin@...>
http://www.cybernaute.com/earthconcert2000/AspartaMalcache.htm
http://www.fedupwithfoodadditives.info/  Australia   FAILSAFE diet
http://www.bradymax.com/nzaa/  New Zealand
http://www.reseauproteus.net/therapies/nutritio/aspartame.htm  France
http://ww2.grn.es/avalls/aspa1.htm   Spain
http://www.geocities.com/HotSprings/Falls/8669/   Brazil
http://www.phd.com.br/aspartame.htm
http://hem.passagen.se/mission.possible.sweden/
http://home.online.no/~dusan/foods/aspartame.html   Norway
http://www.ostara.org/aspartam/#menue  Germany
http://www.aspartaam.nl/info/product.html   Holland, in Dutch
http://www.laleva.org/  <archimede@...>  Italy   9 languages
http://www.laleva.cc/alimenti/alimenti.html  aspartame vs stevia 4.17.03
http://users.westnet.gr/~cgian/aspartame.htm   Greece
http://www.cseindia.org/html/cola-indepth/index.htm India
***********************************************************

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall

Dr. Woodrow C. Monte  Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984;  36 (1):  42-54.
(62 references)   Professsor of Food Science [retired 1992]
Arizona State University,  Tempe, Arizona 85287  woodymonte@...
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame.  The EPA limit for water is 7.8 mg daily
for methanol (wood alcohol), a deadly cumulative poison. Many users
drink 1-2 L daily. The reported symptoms are entirely consistent
with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but,
like all juices, has 16 times more ethanol, which strongly protects
against methanol.)

"Fruit and vegetables contain pectin with variable methyl ester
content. However, the human has no digestive enzymes for pectin (6, 25)
particularly the pectin esterase required
for its hydrolysis to methanol (26).

Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3).  In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6)  (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120 deg C produced
only traces of methanol (3).  Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).  Entrapment of these
volatiles probably accounts for the elevation in methanol levels of certain
fruits and vegetable products during canning (31, 33)."

Recent research [see links at end of post] supports his focus on the
methanol to formaldehyde toxic process:

"The United States Environmental Protection Agency in their Multimedia
Environmental Goals for Environmental Assessment recommends a minimum
acute toxicity concentration of methanol in drinking water at 3.9 parts
per million, with a recommended limit of consumption below 7.8 mg/day
(8). This report clearly indicates that methanol:

"...is considered a cumulative poison due to the low rate of excretion
once it is absorbed.  In the body, methanol is oxidized to formaldehyde
and formic acid; both of these metabolites are toxic." (8)...

Recently the toxic role of formaldehyde (in methanol toxicity) has been
questioned (34).  No skeptic can overlook the fact that, metabolically,
formaldehyde must be formed as an intermediate to formic acid
production (54).

Formaldehyde has a high reactivity which may be why it has not been
found in humans or other primates during methanol posisioning (59)....

If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave.

Formaldehyde is a known carcinogen (57) producing squanous-cell
carcinomas by inhalation exposure in experimental animals (22).  The
available epidemiological studies do not provide adequate data for
assessing the carcinogenicity of formaldehyde in man (22, 24, 57).

However, reaction of formaldehyde with deoxyribonucleic acid (DNA)
has resulted in irreversible denaturation that could interfere with DNA
replication and result in mutation (37)..."

http://www.dorway.com/barua.html
Dr. J. Barua (ophthalmic surgeon), Dr. Arun  Bal (surgeon)
Emerging facts about aspartame.
Journal Of The Diabetic Association Of  India 1995; 35 (4):
(79 references)    barua@...
"...the total amount of methanol absorbed will be approximately
10% of aspartame ingested. An EPA assessment of methanol states
that methanol, 'is considered a cumulative poison due to the low rate
of excretion once it is absorbed.  The absorbed methanol is then
slowly converted to formaldehyde...'"
"Reaction of formaldehyde with DNA has been observed,
by spectrophotometry and electron microscopy, to result in
irreversible denaturation."   "DKP [from aspartame] has been implicated
in the occurence of brain tumors."
************************************************************

http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 1.5.3 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr   gkokotos@...
"K.H. Schulpis" <inchildh@...>  "G.J. Reclos" <reklos@...>

http://groups.yahoo.com/group/aspartameNM/message/960
aspartame & MSG: possible role in autoimmune hepatitis:
Prandota Jan 2003: Murray 1.15.3 rmforall

Roberts, Hyman J., 1924- ,
Useful insights for diagnosis, treatment and public heath: an updated
anthology of original research, 2002, 798 pages,
Palm Beach Institute for Medical Research, Inc.
P.O. Box 17799,  West Palm Beach, FL 33416
fax 561-547-8008   dr.roberts@...
aspartame disease pages 627-685, 778-780

http://groups.yahoo.com/group/aspartameNM/message/859
RTM: Roberts: the life work of a brilliant clinician:
aspartame toxicity 8.2.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/790
RTM: Moseley:
review Roberts "Aspartame Disease: An Ignored Epidemic" 2.7.2  rmforall

http://groups.yahoo.com/group/aspartameNM/message/858
RTM: Samuels: Strong: Roberts: Gold:  flaws in double-blind studies re
aspartame and MSG toxicity  8.1.2 rmforall

"Survey of aspartame studies: correlation of outcome and funding
sources," 1998, unpublished:   http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed
medical literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100%) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91%)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown,
OH 44501    330-740-3621    rwalton193@...
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

http://groups.yahoo.com/group/aspartameNM/message/938
aspartame harms mice brain cells: Hetle & Eltervaag: 2001 thesis
abstract: Sonnewald 1995 study, full text: Murray 1.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/346
WebMD: Barclay: Barth:
survey shows aspartame hurts memory in students 11.9.00
http://www.psy.tcu.edu/psy/barth.htm
Timothy M. Barth Department of Psychology    t.barth@...
Texas Christian University TCU Box 298920 Fort Worth, TX 76129
Chairman, Physiological Psychology   817-921-7410

http://groups.yahoo.com/group/aspartameNM/message/760
Kovatsi L, Tsouggas M
The effect of oral aspartame administration on the
balance of magnesium in the rat.
Magnes Res 2001 Sep;14(3): 189-94.
Laboratory of Forensic Medicine & Toxicology, Faculty of Medicine
Aristotle University of Thessaloniki, Greece  kovatsi@...

http://groups.yahoo.com/group/aspartameNM/message/943
aspartame, cell phones, brain cancer July 1999 Hardell:
Murray 1.9.3 rmforall
http://www.medscape.com/MedGenMed/braintumors
Lennart Hardell, M.D., PhD, in 1999 reported in Sweden that both
cell phone use and heavy aspartame use correlate with increased
brain cancers    lennart.hardell@...   +46 19 602 15 46

http://groups.yahoo.com/group/aspartameNM/message/31
Murray: Wurtman: aspartame & seizures 11.9.85 10.30.99
Wurtman RJ   Aspartame: possible effect on seizure susceptibility.
Lancet 1985 Nov 9; 2(8463): 1060.
Richard J. Wurtman, Ph.D.  dick@...  617-253-3091
Professor of Neuroscience
Prof. of Health Sciences and Technology
Massachusetts Institute of Technlogy  Cambridge, Mass. 02139

http://groups.yahoo.com/group/aspartameNM/message/32
Murray:  Drake: aspartame & panic attacks 9.13.86 10.30.99 rmforall
Miles E. Drake, MD
Panic attacks and excessive aspartame ingestion.
Lancet 1986 Sep 13; 2(8507): 631.
Department of Neurology and Psychiatry,
Ohio State University Medical Center,  Columbus, Ohio 43210, USA

http://www.truthinlabeling.org/    Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD   The toxicity/safety of processed
free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999;  6:  259-310.  52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333   adandjack@...

http://www.msgmyth.com/   Debby Anglesey <avenger@...>
Battling the "MSG Myth", A Survival Guide and Cookbook - $19.00
P.O. Box 895  Richland, WA 99352    509-735-3397

Russell L. Blaylock, MD  601-982-1175  Madison, Mississippi
"Excitotoxins: The Taste that Kills", 1977, 298 p., 493 references.
"Health and Nutrition Secrets that can save your life", 2002, 459 p.,
558 + 30 references, $ 30   http://www.russellblaylockmd.com/

George R. Schwartz, MD "In Bad Taste: The MSG Syndrome", 1988
http://www.healthpress.com/  goodbooks@...
PO Box 37470 Albuquerque, NM 87176 505-888-1394
Kathleen Frazier, Publisher

http://groups.yahoo.com/group/aspartameNM/message/841
RTM: Merisant Co., MSD Capital, Dell Computer Corp., NutraSweet Co.,
JW Childs Assc.: aspartame-neotame toxicity 7.10.2 rmforall
****************************************************************

http://www.vegsource.com  extensive vegan information
http://www.vegsource.com/articles/kradjian_milk.htm
Robert Kradjian MD Discusses Milk

http://groups.yahoo.com/group/aspartameNM/message/971
Joel Fuhrman critique of Atkins diet in "Eat To Live":
Murray 3.1.3 rmforall

Substitute stevia (at health food stores).
Avoid all products with aspartame and MSG. Gradually reduce alcohol,
caffeine (coffee, cocoa, and teas), meat, fish, eggs, milk, butter, and
cheese, food additives and colors, fluoride, city water.  Enjoy organic
rice, beans, nuts, almond butter, vegetables, fruits, with modest use of
soy products and sprouted grain breads, flax seed and olive oils, vitamins
and minerals, 4-8 1,000 mg fish oil capsules, and fill your jugs with
deionized water.
*****************************************************************

************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 3.30.4 rmforall   [ 150 KB ]

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

[ Comments by Rich Murray are in square brackets.  To increase the
readability of the dense, specialized, condensed text of a brief scientific
letter (usually not peer reviewed), I have added spacing without altering
text, while correcting minor typos.

I then offer some critical analyses and extensions of the references, since
the relevant scientific literature is contaminated by long-term, systematic
influence by corporate vested interests. ]

"A 60-year-old Caucasian woman presented with a 6-month history of eyelid
dermatitis...

By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.

Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.

She had begun using an aspartame-based artificial sweetener 5 months prior
to the onset of her dermatitis. [ 12 months of low-level aspartame use until
stopping. ]

Within 1 week of discontinuing the aspartame, her eyelid dermatitis resolved
completely and has not recurred over 18 months without specific
treatment....

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied."

[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet
soda gives 200 mg aspartame.  An aspartame reactor can have immediate strong
symtoms from an under-the-tongue wafer with 4 mg aspartame.  (Appendix A,
for comments, abstracts, and links.) ]

Contact Dermatitis. 2003 Nov; 49(5): 258-9.
Systemic contact dermatitis of the eyelids caused by formaldehyde derived
from aspartame?
Hill AM, Belsito DV.   DBelsito@...
Division of Dermatology, University of Kansas Medical Center, 3901 Rainbow
Blvd., Kansas City, KS 66160, USA.     PMID: 14996049

A. Michele Hill and Donald V. Belsito
Division of Dermatology, University of Kansas Medical Center
3901 Rainbow Blvd., Kansas City, KS 66160, USA  [ (Appendix B, for more
abstracts by Donald V. Belsito, selections, and institutions) ]

Key Words: allergic contact dermatitis; aspartame; eyelids; formaldehyde;
systemic contact dermatitis.

Formaldehyde is a common and ubiquitous contact allergen.
Sources of exposure include hair and skin care products, cosmetics, topical
medications, permanent press clothing, cleaning agents, disinfectants, paper
and even smoke. [ Also, new buildings, mobile homes,  furniture, carpets,
drapes, particleboard,  medical facilities, methanol, aspartame, dimethyl
dicarbonate, dark wines and liquors   ]

Sensitization is reported in between 2.2 and 9.6% of patients patch tested
(1,2).
[ (Appendix C, for abstracts on rates of formaldehyde sensitivity in control
groups, as a possible first estimate of the impact of widespread exposure to
aspartame since 1981.) ]

Case Report

A 60-year-old Caucasian woman presented with a 6-month history of eyelid
dermatitis.
A corticosteroid-containing opthalmologic ointment improved but did not
clear the rash.
She failed to improve when she discontinued the use of all eyelid cosmetics
and nail polishes for 2 months.
She had had a facial dermatitis in 1995, for which she had been patch tested
and found to be allergic to formaldehyde, quaternium-15 and fragrances.
She had also had incidental, non-relevant reactions to neomycin and
ethylenediamine.
Her dermatitis had resolved with a change to formaldehyde-, quaternium-15
and fragrance-free facial and nail cosmetics.

There was no personal or family history of atopy or psoriasis.
Her only oral medication was celecoxib that she had taken for years prior to
the onset of her blepharitis.
She had also taken multivitamins, calcium and flaxseed oil for many years.
She worked as a homemaker and library volunteer. [ It is relevant as to
whether she had the standard urban diet with high protein and animal fats,
meats, milk products, some  inorganic fruits and vegetables, high sugars,
and processed foods.  Mercury dental amalgams and mercury contaminated fish
could also play a role.  Was her water fluoridated or otherwise
contaminated?  Were there toxic mold exposures in her environment?  Was she
exposed to pesticides in her area?  ]

Her eyelid dermatitis was kept clear with tacrolimus 0.03% ointment X2
daily.
She underwent patch testing to the North American Contact Dermatitis Group
standard tray, the University of Kansas' supplemental standard tray, and to
her cosmetics, cleansers, skin and hair care products and topical
medications.
She had relevant positive reactions at days 2 and 4 to formaldehyde (++),
quaternium-15 (++), diazolidinyl urea (+), DMDM hydantoin (+) and
imidazolidinyl urea (++), her hair care products and cleansers containing
multiple sources of these allergens.

She was extensively instructed in avoidance of formaldehyde and formaldehyde
releasers, as well as that of her multiple, currently non-relevant
allergens, including fragrance, benzalkonium chloride, neomycin, bacitracin,
p-phenylenediamine and black rubber mix.   [ As a medical layman, I'm
disturbed to see all these chemicals that I know nothing about. ]

By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.

Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.

She had begun using an aspartame-based artificial sweetener 5 months prior
to the onset of her dermatitis. [ 12 months of low-level aspartame use until
stopping. Aspartame reactors discover this possibiliy usually from the Net,
alternative medicine providers, media, nurses, friends, and pharmacists,
rarely from physicians. ]

Within 1 week of discontinuing the aspartame, her eyelid dermatitis resolved
completely and has not recurred over 18 months without specific treatment.
[ This quick healing response is typical of cases of low-level use with few
symptoms.  Long-term heavy users , above 2 L, about 6 12-oz cans daily for
years, often have severe craving and withdrawal symptoms for weeks, with
gradual recovery for months.  H. J. Roberts, MD has summarized over 1200
cases.  (Appendix H)   Three recent case reports are added here.
(Appendix I) ]

Unfortunately, she refused to undergo rechallenge with the sweetener.
[  This is usually the case.   Commonly, there is inadvertent reexposure,
with immediate painful symptoms, even with low doses. ]

Discussion

The artificical sweetener, aspartame, is consumed by 54% of adults in the
USA (3).

It has been reported to cause dry eyes and difficulty in wearing contact
lenses (3) but never allergic contact dermatitis. [ Reference (3)  is given
in full  here. (Appendix H)   Roberts H J.  Dry eyes from use of aspartame
(Nutrasweet):  Associated insights concerning the Sjogren syndrome.
The Townsend Letter for Doctors, January 1994.   Appendix H also quotes
several cases of eyelid dermatitis from his review of 1200 cases in
Aspartame Disease: An Ignored Epidemic (2001). ]

Aspartame, an L-aspartyl-L-phynylalanine methyl ester, is hydrolysed in the
intestine to phenylalanine (50%), aspartic acid (40%) and aspartaic acid
methyl ester (10%).

The methyl ester is then converted to methyl alcohol (methanol) and carried
by the portal vein to the liver.

Methanol is there oxidized to formaldehyde that is converted into formic
acid (formate) by alcohol dehydrogenase, aldehyde dehydrogenase and the
microsomal oxidase pathway.

This occurs not only in the liver, but also in other organs containing high
levels of these enzymes, including the eye (4,5).

Formaldehyde binds proteins and nucleic acids, forming adducts difficult to
eliminate via metabolism.

Trocho et al. (6) demonstrated the formation of formaldehyde adducts with
DNA and proteins after administration of 20 mg/kg 14C-labelled aspartame to
rats, concluding that these adducts were responsible for functional
alterations of proteins and for DNA mutations leading to autoimmunity, cell
death or malignant transformation.  [ (Appendix E) gives links, comments,
and quotes for the debate on the key Trocho study. ]

In contrast to Trocho et al. (6), McMartin et al. (7) studied formaldehyde
levels after large doses (3,000 mg/kg) of 14C-labelled methanol and
14C-labelled formaldehyde in monkeys, which unlike rats are sensitive to the
toxicities of methanol.

No increased formaldehyde derived from methanol was found.

High levels of formic acid were found in all monkeys that were given
methanol or formaldehyde.

[ (Appendix F) reviews the major studies.  Oppermann et al (1973, 1976)
found that 30% of the methanol from aspartame fed to monkeys remained in
body tissues, indubitably as toxic products of formaldehyde and formic acid.
They did not test methanol product  retention in humans.  McMartin et al
(1979) reported significant formaldehyde retention in the midbrain of one
monkey from oral aspartame, and substantial formic acid in liver, kidney,
optic nerve, cerebrum, and midbrain in two other monkeys.  It is clear that
his formaldehyde assays were too insensitive to give valid measurements.
There has been a dearth of relevant primate and human studies ever since. ]

Based on the work of McMartin and al. (7), Tephly (8) concluded that the
radioactive carbon from methanol, which was found in DNA and protein by
Trocho et al., was due to the normal physiologic flow of single-carbon units
through the folate pathway.

Stegink et al. (9) have shown that doses of 100 mg/kg or greater of
aspartame are required to increase methanol blood levels (and thus,
presumable formaldehyde formic acid levels) above control.

This would be equivalent to consuming 35 cans of diet beverage at one
sitting for a 70 kg person.  [ This is a typical aspartame industry PR ploy,
well designed to plant the impression that only absurdly huge amounts of
diet soda might supply damaging amounts of methanol-derived formaldehyde and
formic acid toxic residuals in body tissues, thus reducing methanol blood
levels.  So, it is a classic red herring tactic to focus on methanol blood
levels.

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12 mg
daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

[ http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall ]

This long-term low-level chronic toxic exposure leads to typical patterns of
increasingly severe complex symptoms, starting with headache, fatigue, joint
pain, irritability, memory loss, and leading to vision and eye problems, and
even seizures. In many cases there is addiction.  Probably there are immune
system disorders, with a hypersensitivity to these toxins and other
chemicals.
(Appendixes D, E, F, G, H, I, J) ]

Leon et al. (10) studied doses of 75 mg/kg of aspartame daily for 24 weeks
and found no change in blood or urine methanol levels and no symptoms of
methanol toxicity.

The dose used in Leon's study is 25 times the 90th percentile daily
consumption of aspartame (11). [ Appendix E gives an abstract by Davoli
(1986), using a properly sensitive assay,  that proved a temporary rise in
blood methanol levels in humans from a single aspartame dose.  Trocho
pointed out that formaldehyde adducts are persistent and thus cumulative. It
is reasonable to state that with long-term chronic formaldehyde exposure, it
may take a long time to both accumulate adducts and develop markedly
increased sensitivity and a series of complex symptoms .  Adequate studies
would have to test substantial exposures over a year or longer with large
numbers of vulnerable types of people and record all symptoms. ]

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied.
[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet
soda gives 200 mg aspartame.  An aspartame reactor can have immediate strong
symtoms from an under-the-tongue wafer with 4 mg aspartame.  (Appendix A,
for comments, abstracts, and links.) ]

However, it is possible that the eye, with its high level of metabolic
activity, could be affected by methanol (and subsequently formaldehyde)
released from these low levels of aspartame and respond as a localized
target organ to minute amounts of her known allergen, formaldehyde, or its
metabolite, formate.

It is also possible that the amplifying effects of cell-mediated immunity
might detect trace amounts of a chemical not identified by more standard
assays, such as blood or urine levels. [ (Appendix D gives Thrasher's data
about immune system reactions from long-term, low-level formaldehyde
exposure, while Martin Pall gives a complex general theory, specifically
discussing formaldehyde as a major trigger.)

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame: Martin L. Pall: Murray:
12.9.2 rmforall

FASEB J 2002 Sep; 16(11): 1407-17.
NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and
organic solvents as the mechanism of chemical sensitivity in multiple
chemical sensitivity.
Pall ML.    PMID: 12205032    [ 162 references, received 1.3.2 ]
School of Molecular Biosciences, Washington State University,
Pullman, Washington 99164-4660, USA.   martin_pall@... ]

Such a hypothesis might explain why her dermatitis was limited to the
eyelids and give clinical support to Trocho's theory of formaldehyde
adducts.

Unfortunately, without rechallenging her with aspartame, we cannot test this
hypothesis.

Nonetheless, her long-lasting remission following discontinuation of
aspartame intake suggests that its breakdown to formaldehyde may have been a
possible mechanism for her prior blepharitis.

References

1. Christophersen J, Menne' T, Tanghoj P, Andersen K E, Brandrup F.
Clinical patch test data evaluated by multivariate analysis.
Contact Dermatitis 1989: 21: 291-299.

2. Fransway AF, Schmitz N A.
The problem of preservation in the 1990s.
II. Formaldehyde and formaldehyde-releasing biocides: incidences of
cross-reactivity and the significance of the positive response to
formaldehyde.
Am J Contact Dermat. 1991: 2: 78-88.

3. Roberts H J. Dry eyes from use of aspatame (Nutrasweet):
Associated insights concerning the Sjogren syndrome.
The Townsend Letter for Doctors, January 1994. [ full text in Appendix H ]

4. Murray T G, Burton T C, Rajani C, Lewandowski M F,
Burke J M, Eells J T.
Methanol poisoning: A rodent model with structural and functional evidence
for reinal involvement.
Arch Opthalmol 1991: 109: 1012-1016.

5. Eells J T.
Methanol-induced visual toxicity in the rat.
J. Pharmacol Exp Ther 1991: 257: 56-63.

6. Trocho C., Pardo R, Fafecas I, Virgili J, Remesar X,
Fernandez-Lopez, J A.
Formaldehyde derived from dietary aspartame binds to tissue components in
vivo.
Life Sci 1998 1988: 63: 337-349. [ abstract and quotes in Appendix E )

7. McMartin K E, Mrtin-Amat G, Noker P E, Tephly T R.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Biochem Pharmacol 1979: 28: 645-649. [ abstract, quotes, discussion, related
studies in Appendix F ]

8. Tephly T R: Comments on the purported generation of formaldehyde from
the sweetener aspartame.
Life Sci 1999: 65: 157-160.   [ letter, usually not peer-reviewed,
abstract in Appendix E  ]

9. Stegink L D, Brummel M C, McMartin-Amat G., Filer L J, Baker G L,
Tephly T R.
Blood methanol concentrations in normal adult subjects administered abuse
doses of aspatame.
J Toxicol Environ Health 1981: 7: 281-290.

10. Leon A S, Hunninghake D B, Bell C, Rassin D K, Tephly T R.
Safety of long-term large doses of aspartame.
Arch Intern Med 1989: 149: 2318-2324.

11. Tschanz C., Butachko H, Stargel W, Kotsonis F N (eds).
The Clinical Evaluation of a Food Additive: Assessment of Aspartame
Boca Raton: CRC Press, 1996.
************************************************************

Appendix A:

http://groups.yahoo.com/group/aspartameNM/message/846
aspartame in Merck Maxalt-MLT worsens migraine,
AstraZeneca Zomig, Eli Lilly Zyprexa,
J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab,
Pfizer Cool Mint Listerine Pocketpaks: Murray 7.16.2 rmforall

Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB  Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology   newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research   RLipton@...

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall

Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches. Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA.   neurotulsa@...
Aspartame, a popular dietetic sweetener, may provoke headache in some
susceptible individuals. Herein, we describe three cases of young women
with migraine who reported their headaches could be provoked by chewing
gum sweetened with aspartame. [ 6-8 mg aspartame per stick chewing gum ]

http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 1.17.2 rmforall

Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following Discontinuation of Dietary
Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is
often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome
for two to 17 years are described.
All had undergone multiple treatment modalities with limited success.
All had complete, or nearly complete, resolution of their symptoms within
months after eliminating monosodium glutamate (MSG) or MSG plus aspartame
from their diet.
All patients were women with multiple comorbidities prior to elimination of
MSG.
All have had recurrence of symptoms whenever MSG is ingested.
PMID: 11408989

Siegfried O. Schmidt, MD  Asst. Clinical Prof.  siggy@...
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
352-376-5071

Several recent pro-aspartame reviews simply ignore these reports by eminent
mainstream researchers, as well as the tidal surge of complaints by users.

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall  EU Scientific Committee on Food, a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame (12.4.2): 59 pages, 230 references

J Am Diet Assoc. 2004 Feb; 104(2): 255-75.
Position of the American Dietetic Association: use of nutritive and
nonnutritive sweeteners.
American Dietetic Association.    PMID: 14760578

http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review by American Dietetic Association Feb 2004:
Murray 4.1.4 rmforall

"Survey of aspartame studies: correlation of outcome and funding sources,"
1998, unpublished:   http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed medical
literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100%) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91%)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown,
OH 44501    330-740-3621    rwalton193@...
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

http://groups.yahoo.com/group/aspartame/messages 770 members 16,692 posts  ]
************************************************************

Appendix B:

D. V. Belsito has 71 items in PubMed since 1982.

Donald (Don) V. Belsito, MD   Professor, Division Director  Dermatology
  +1 913 588-3840  fax +1 913 588-4060      DBelsito@...
Main Phone Number: (913) 588-6028   Fax Number: (913) 588-8300
Mailing Address:  4008 Wescoe Pavilion Mail Stop 2025
3901 Rainbow Boulevard, Kansas City, KS 66160-7319 USA

The University of Kansas Medical Center
3901 Rainbow Boulevard, Kansas City, KS 66160
913-588-5000, 913-588-7963 TDD                   KU Medical Center is a
campus of the University of Kansas and is affiliated with The University of
Kansas Hospital. The School of Medicine has a campus in Wichita.

http://www.centerwatch.com/professional/pro503.html
University of Kansas Medical Center Research Institute
3901 Rainbow Boulevard, Kansas City, KS 66160-7702 USA
Phone: 913-588-1242  Fax: 913-588-5729    lkemble@...

The University of Kansas Medical Center comprises the School of Medicine,
School of Allied Health, School of Nursing, and an independently run
hospital with 415 staffed beds. KUMC is a regional health center treating
approximately 35,000 emergency room patients, 17,000 inpatients, and more
than 180,000 outpatients per year. KUMC is a 35 building, 50 acre campus
with a staff of nearly 5,000 employees.

The University of Kansas Medical Center Research Institute is a private,
non-profit corporation established to promote and support medical research.
The Division of Clinical Trials at the Research Institute serves as the
central liaison between the pharmaceutical industry, faculty investigators
at KUMC, and the Institutional Review Board. The Division of Clinical Trials
also assists the sponsor with identifying suitable clinical investigators.

http://author.emedicine.com/DERM/topic549.htm
Dermatologic Manifestations of Neurologic Disease
Authored by Theresa Conologue, DO, Staff Physician, Department of
Dermatology, National Capital Consortium/Walter Reed Army Medical Center
Coauthored by Jeffrey Meffert, MD, Program Director, Dermatology Service,
San Antonio Uniformed Services Health Education Consortium.
Theresa Conologue, DO, is a member of the following medical societies:
Association of Military Surgeons of the US
Edited by Donald Belsito, MD, Program Director, Professor, Department of
Internal Medicine, Division of Dermatology, University of Kansas; Richard
Vinson, MD, Chief, Department of Dermatology, William Beaumont Medical
Center; Jeffrey P Callen, MD, Chief, Professor, Department of Internal
Medicine, Division of Dermatology, University of Louisville School of
Medicine; Catherine Quirk, MD, Clinical Assistant Professor, Department of
Dermatology, Brown University; and Dirk M Elston, MD, Consulting Staff,
Department of Dermatology, Geisinger Medical Center
Author's Email: Theresa Conologue, DO   Editor's Email: Donald Belsito, MD
eMedicine Journal, March 19 2003, Volume 4, Number 3
INTRODUCTION Section 2 of 12

Many disorders have a combination of neurologic and dermatologic findings in
patients. This chapter provides an overview of neurocutaneous disorders and
organizes them into clinically relevant groupings of use to the practicing
physician.

http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3564t1.pdf
Center for Drug Evaluation
Dermatologic and Opthalmic Drugs Advisory Commitee
Thursday, November 4, 1999
Ballroom, Hilton Hotel, 620 Perry Parkway, Taithersburg Maryland
Guest Speaker: Donald Belsito, M.M.
6516 Aberdeen Road, Mission Hills, KS 66208

http://www.simplywhispers.com/htdocs/html/Press%20Releases/bodypiercing.html
Dr. Donald Belsito, professor of Dermatology at the University of Kansas in
Lawrence and a member of the North American Contact Dermatitis Group, notes,
"Nickel allergies are on the increase - from 10.5 % cited in studies done
from 1985 to 1989 to 14.3 % in studies done in 1996. More men are showing up
with nickel allergies; coincidentally more men are having their bodies
pierced. This indicates a possible correlation between piercing and
allergies to nickel." In addition to setting off allergic reactions, Dr.
Belsito, notes, "Piercing cartilage around the top of the ear poses greater
risks than piercing the lobe. Cartilage is an inert material with very
little blood supply and takes a long time to heal from the puncture. Also,
when cartilage becomes infected, it is difficult to treat because of its low
blood supply.

"Also, the growth of overwhelming scars known as keloids can occur and the
condition is particularly prevalent among African Americans," says Dr.
Belsito, adding, "Keloids can grow to be as big as the ear itself. The cure
requires administering medication that reduces the tendency to develop
scars. If scars do develop, they need to be removed by a plastic surgeon.
The risk, of course, is that people who tend to scar, may not fare well in
surgery which can promote new scar tissue."  When it comes to protecting the
consumer, Dr. Belsito adds, "I think hypoallergenic is a bad term since it
only tells you that the product is manufactured without an ingredient to
which most people are allergic. But it doesn't tell you other possible
allergy provoking ingredients. For example, some rubber gloves labeled
hypoallergenic are made without certain chemicals. However, these gloves
could be made of latex which is lethal to some people."

Drs. Bendetsen, Scheinman and Belsito favor legislation governing body
piercing due to the risk of nickel allergies, loss of sensation and
communicable diseases resulting from poor sterilization procedures. To date,
Arizona, California, Georgia, Michigan and Washington have passed
legislation requiring parental consent for body piercing if you are a minor.
Several states including Delaware, Missouri, Texas and Hawaii have
legislation pending.

D. V. Belsito has 9 additional items that include formaledhyde in PubMed:

2. Ravis SM, Shaffer MP, Shaffer CL, Dehkhaghani S, Belsito DV.
Glutaraldehyde-induced and formaldehyde-induced allergic contact dermatitis
among dental hygienists and assistants.
J Am Dent Assoc. 2003 Aug; 134(8): 1072-8. PMID: 12956347

3: Thompson TR, Belsito DV.
Regional variation in prevalence and etiology of allergic contact
dermatitis.
Am J Contact Dermat. 2002 Dec; 13(4): 177-82.  PMID: 12478532

4: Rietschel RL, Mathias CG, Fowler JF Jr, Pratt M, Taylor JS, Sherertz EF,
Marks JG Jr, Belsito DV, Storrs FJ, Maibach HI, Fransway AF, Deleo VA;
North American Contact Dermatitis Group.
Relationship of occupation to contact dermatitis: evaluation in patients
tested from 1998 to 2000.
Am J Contact Dermat. 2002 Dec; 13(4): 170-6.  PMID: 12478531

5: Deleo VA, Taylor SC, Belsito DV, Fowler JF Jr, Fransway AF, Maibach HI,
Marks JG Jr, Mathias CG, Nethercott JR, Pratt MD, Reitschel RR, Sherertz EF,
Storrs FJ, Taylor JS.
The effect of race and ethnicity on patch test results.
J Am Acad Dermatol. 2002 Feb; 46(2 Suppl Understanding): S107-12.
PMID: 11807472

6: Suneja T, Belsito DV.
Comparative study of Finn Chambers and T.R.U.E. test methodologies in
detecting the relevant allergens inducing contact dermatitis.
J Am Acad Dermatol. 2001 Dec; 45(6): 836-9.   PMID: 11712026

7: Suneja T, Belsito DV.
Thimerosal in the detection of clinically relevant allergic contact
reactions.
J Am Acad Dermatol. 2001 Jul; 45(1): 23-7.  PMID: 11423830

8: Shaffer MP, Belsito DV.
Allergic contact dermatitis from glutaraldehyde in health-care workers.
Contact Dermatitis. 2000 Sep; 43(3): 150-6. Review.  PMID: 10985631

9: Marks JG, Belsito DV, DeLeo VA, Fowler JF Jr, Fransway AF, Maibach HI,
Mathias CG, Nethercott JR, Rietschel RL, Sherertz EF, Storrs FJ,
Taylor JS.
North American Contact Dermatitis Group patch test results for the
detection of delayed-type hypersensitivity to topical allergens.
J Am Acad Dermatol. 1998 Jun; 38(6 Pt 1): 911-8.  PMID: 9631997

10: Fowler JF Jr, Skinner SM, Belsito DV.
Allergic contact dermatitis from formaldehyde resins in permanent press
clothing: an underdiagnosed cause of generalized dermatitis.
J Am Acad Dermatol. 1992 Dec; 27(6 Pt 1): 962-8.  PMID: 1479102
************************************************************

Appendix C:

"Sensitization is reported in between 2.2 and 9.6% of patients patch tested
(1,2)."

Widespread use of aspartame since 1981 must cause some of the formaldehyde
sensitization found in many studies of control groups, so I offer a relevant
abstract, which is the only data I know of that starts to assess
the prevalence of aspartame disease in otherwise healthy people:

"One (2 percent) control subject had a reaction to glutaraldehyde, and one
other (2 percent) had a reaction to formaldehyde."   "51 nondental
professionals "

Aspartame use must sensitize some users.  This study's control group hints
that about 2% of a control group of 51 professionals showed a sensitivity to
formaldehyde in a skin patch test.  Are there any data for nonusers of
aspartame?

J Am Dent Assoc. 2003 Aug; 134(8): 1072-8.
Glutaraldehyde-induced and formaldehyde-induced allergic contact dermatitis
among dental hygienists and assistants.
Ravis SM, Shaffer MP, Shaffer CL, Dehkhaghani S, Belsito DV.
University of Miami, USA.

BACKGROUND: Research has found that among health care workers, dental
personnel are especially likely to have reactions to glutaraldehyde and
formaldehyde.
METHODS: The authors conducted patch test evaluations with a voluntary
cohort of randomly recruited, healthy dental hygienists, or DHs,
and dental assistants, or DAs, and nondental professionals
to determine the incidence of glutaraldehyde-induced and
formaldehyde-induced allergic contact dermatitis, or ACD;
the potential for coreactivity between glutaraldehyde and formaldehyde; and
the correlation between training methods in safe handling of sterilizing
solutions and the sensitivity to glutaraldehyde and formaldehyde among DHs
and DAs.
RESULTS: The researchers enrolled 101 DHs and DAs and 51 nondental
professionals in the study.
All except one DH/DA subject were female.
The dental subjects' mean age was 34.3 +/- standard deviation of 10.7 years;
the nondental subjects', 33.8 +/- 11.0 years.
DHs and DAs had worked in their profession for a mean of 11.0 +/- 9.3 years.
Among the dental professionals, 80 (79.2 percent) had had a known exposure
to cold sterilizing solutions, while the remainder were unable to provide a
known history of exposure.
Eleven (10.9 percent) dental professionals had clear reactions to
glutaraldehyde,
four (4.0 percent) were questionably allergic to glutaraldehyde, and
two (2 percent) were definitively allergic to formaldehyde.
One (2 percent) control subject had a reaction to glutaraldehyde, and
one other (2 percent) had a reaction to formaldehyde.
CONCLUSIONS AND CLINICAL: IMPLICATIONS: The authors found a statistically
significant disparity in the rates of glutaraldehyde sensitivity among
healthy DHs and DAs versus healthy control subjects (10.9 percent versus 2
percent reactively; P = .02).
They found no evidence of cross-reactivity between glutaraldehyde and
formaldehyde. The preponderance of reactions among the DHs and DAs suggests
that their present safety practices are largely ineffective in protecting
against sensitization to glutaraldehyde in sterilizing solutions.  PMID:
12956347
************************************************************

Appendix D:

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

Environ Health Perspect. 2003 Sep; 111(12): 1461-4.
Elevated nitric oxide/peroxynitrite theory of multiple chemical sensitivity:
central role of N-methyl-D-aspartate receptors in the sensitivity mechanism.
Pall ML.
School of Molecular Biosciences, 301 Abelson Hall, Washington State
University, Pullman, WA 99164, USA.  martin_pall@...

The elevated nitric oxide/peroxynitrite and the neural sensitization
theories of multiple chemical sensitivity (MCS) are extended here to propose
a central mechanism for the exquisite sensitivity to organic solvents
apparently induced by previous chemical exposure in MCS.
This mechanism is centered on the activation of N-methyl-D-aspartate (NMDA)
receptors by organic solvents producing elevated nitric oxide and
peroxynitrite, leading in turn to increased stimulating of and
hypersensitivity of NMDA receptors.
In this way, organic solvent exposure may produce progressive sensitivity to
organic solvents.
Pesticides such as organophosphates and carbamates may act via muscarinic
stimulation to produce a similar biochemical and sensitivity response.
Accessory mechanisms of sensitivity may involve both increased blood-brain
barrier permeability, induced by peroxynitrite, and cytochrome P450
inhibition by nitric oxide. The NMDA hyperactivity/hypersensitivity and
excessive nitric oxide/peroxynitrite view of MCS provides answers to many of
the most puzzling aspects of MCS while building on previous studies and
views of this condition.  PMID: 12948884

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

"Inhalation exposure to formaldehyde (HCHO)
is associated with symptoms of irritation to mucous membranes, (1,2)
chronic health problems (e.g., asthma, (2) nasopharyngeal cancer, (3)
and multiple subjective health complaints. (4,5) )
Recent observations have shown that both humoral-and cell-mediated
immunologic mechanisms occur in humans with long-term HCHO exposure.
Antibodies of all isotypes to HCHO conjugated human serum albumin (HCHO-HSA)
are demonstrable in HCHO anaphylaxis, (6) hemodialysis patients, (7)  mobile
home residents, (4) persons with occupational exposures, (5,8)  office
workers, (9) and in persons in other environments. (4)
In addition, changes in cell-mediated immunity include increases in
eosinophils, basophils, and T-suppressor cells following acute exposure of
patients with HCHO asthma. (10)
Moreover, individuals with multiple subjective health complaints associated
with long-term HCHO inhalation have evidence of immune activation and the
presence of autoantibodies. (4,5)

The patients in our study had symptoms and complaints related to several
organs, as described previously, (4,5,9)  which were similar to symptoms of
workers with multiple chemical sensitivity,(11) cacosmia,(12) and other
chemical exposures. (13-15)   We report on the differences in humoral and
cell-mediated immunity in humans with long-term inhalation exposure to HCHO
vs. asymptomatic students (controls) who experienced short-term, periodic
exposure to the chemical."
[ http://lassesen.com/cfids/cacosmia.htm
Cacosmia (a.k.a. Multiple Chemical Sensitivity)  Details:
* Chemical odour intolerance induced headache, itching eyes, irritated or
congested nose, dry and/or sore throat, cough, dizziness, and itching or
rash.
*  Cacosmics reported increased prevalence of physician-diagnosed nasal
allergies, breast cysts, hypothyroidism, sinusitis, food sensitivities,
irritable bowel, and migraine headache.  Resource: http://www.mcsrr.org ]

"Symptoms. All patients in this study had sought continuous medical
attention because of multiple organ symptoms involving the central nervous
system (CNS)  (headaches, memory loss, difficulty completing tasks,
dizziness), upper- and lower-respiratory symptoms, skeletal-muscle
complaints, and gastroenteritis.  Three common symptoms
were expressed:
[1.] and initial flu-like illness from which they had not fully
recovered; [2.] chronic fatigue;  and [3.] an olfactory sensitivity to
ambient conditions containing low concentrations of chemicals.  (4,9,11)"

"It is recognized that chemicals and therapeutic drugs are associated
with a Lupus-like syndrome. (28,29 )  The observations made on the
patients in this study support this concept."

"Five groups of subjects exposed to HCHO,
who gave informed consent, were included in this study.
[1.]  Controls consisted of students of chiropractic medicine
(16 males, 12 females), mean age = 29 +- 9 y) exposed to HCHO
for 13 h/wk for 28 wk while studying human anatomy.   Immunologic tests
were performed 12 mo following the last classroom exposure.
No measurements of HCHO concentrations were made.
It is assumed that classroom ambient concentrations were at least
0.43 ppm. (1)   The students stated that during exposure they experienced
eye, nose and throat irritation and that there was a pungent odor of
HCHO.   They did not have residual health complaints (symptoms), and
they were asymptomatic at the time blood was taken.
[2.]  Mobile home residents consisted of 19 patients (6 males, 13 females),
mean age 41+-20 y) who currently lived in mobile homes.   The patients had
lived in their environments for 2-7 y and reported multiple symptoms. (4,9)
Measured HCHO concentrations ranged from 0.05 to 0.5 ppm at the time
blood samples were taken.
[3.]  Office workers included 21 patients
(5 males, 16 females, mean age of 40 +-10 y)
who worked in new office buildings where there was inadequate ventilation
(closed buildings).  The patients had multiple health complaints. (9)
It was determined from medical histories that their symptoms commenced
with employment, waned when away from work (i.e., weekends, holidays,
vacations) and became worse upon return to work.
No HCO measurements were done;  however, closed buildings have ambient
concentrations ranging from 0.01 to 0.77 ppm. (1,16)
[4.]  This group included 21 patients (10 males, 11 females,
mean age of 35 + -17 y) who had multiple symptoms and who had been
removed from their original sources of HCHO exposure (mobile homes
and/or particleboard subflooring) for at least 1 y.   The HCHO
concentrations measured during their exposures ranged from 0.14 to 0.81 ppm.
[5.]  Ocupationally exposed patients
(6 males, 2 females, mean age of 45 + -11 y)
had HCHO exposures from the following:  biology and human
anatomy classes, mortuary, pathology, physical therapy, formica
furniture (particleboard), and carbonless copy paper.  Information on
six of these patients was previously published. (5)"

"In conclusion, measurements of changes in WBCs, T cells, and H/S
ratios in individuals with apparent chemical sensitivities appear to be
inadequate immune parameters to examine.   If one assumes that these
individuals respond immunogically to environmental chemicals,
investigations into autoimmunity and immune activation and
perturbations in the interleukins, luekotreines, prostglandins, and
other immunologic mediators appear to be fruitful areas for further
research. (29-32)    Thus, it appears that HCHO sensitivity is a real
phenomenon and requires further research. (4,27-32 )"
************************************************************

Appendix E:

"In all, the rats retained, 6 hours after administration, about 5% of the
label, half of it in the liver."

They used a very low level of aspartame ingestion, 10 mg/kg, for rats, which
have a much greater tolerance for aspartame than humans.  So, the
corresponding level for humans would be about 1 or 2 mg/kg. (Many headache
studies in humans used doses of about 30 mg/kg daily.)

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html  full text
Formaldehyde derived from dietary aspartame binds to tissue components in
vivo.
Life Sci June 26 1998; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular,
Facultat de Biologia, Universitat de Barcelona, Spain.
http://www.bq.ub.es/cindex.html    Línies de Recerca: Toxicitat de
l'aspartame     http://www.bq.ub.es/grupno/grup-no.html
Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas,
Sr. Jordi Virgili, Dr. Xavier Remesar,  Dr. Jose Antonio
Fernandez-Lopez, Dr. Marià Alemany [male]
Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
Sra. Carme Trocho "Trok-ho"  Fac. Biologia Tel.:   (93)4021544,
FAX: (93)4021559
alemany@...  bioq@...  josefer@...
rafecas@...  remesar@...

Abstract:
Adult male rats were given an oral dose of 10 mg/kg aspartame,
14C-labeled in the methanol carbon.
At timed intervals of up to 6 hours, the radioactivity in plasma and several
organs was investigated.
Most of the radioactivity found (>98% in plasma, >75% in liver) was bound to
protein.
Label present in liver, plasma and kidney was in the range of 1-2% of total
radioactivity administered per g or mL, changing little with time.
Other organs (brown and white adipose tissues, muscle, brain, cornea and
retina) contained levels of label in the range of 1/12th to 1/10th of that
of liver.
In all. the rats retained, 6 hours after administration, about 5% of the
label, half of it in the liver.

The specific radioactivity of tissue protein, RNA and DNA was quite uniform.
The protein label was concentrated in amino acids, different from
methionine, and largely coincident with the result of protein exposure to
labeled formaldehyde.
DNA radioactivity was essentially in a single different adduct base,
different from the normal bases present in DNA.
The nature of the tissue label accumulated was, thus, a direct consequence
of formaldehyde binding to tissue structures.

The administration of labeled aspartame to a group of cirrhotic rats
resulted in comparable label retention by tissue components, which suggests
that liver function (or its defect) has little effect on formaldehyde
formation from aspartame and binding to biological components.
The chronic treatment of a series of rats with 200 mg/kg of non-labeled
aspartame during 10 days results in the accumulation of even more label when
given the radioactive bolus, suggesting that the amount of formaldehyde
adducts coming from aspartame in tissue proteins and nucleic acids may be
cumulative.

It is concluded that aspartame consumption may constitute a hazard because
of its contribution to the formation of formaldehyde adducts.
PMID: 9714421

[ Extracts ]
"The high label presence in plasma and liver is in agreement with the
carriage of the label from the intestine to the liver via the portal vein.
The high label levels in kidney and, to a minor extent, in brown adipose
tissue and brain are probably a consequence of their high blood flows (45).
Even in white adipose tissue, the levels of radioactivity found 6 hours
after oral administration were 1/25th those of liver.  Cornea and retina,
both tissues known to metabolize actively methanol (21,28) showed low levels
of retained label.  In any case, the binding of methanol-derived carbon to
tissue proteins was widespread, affecting all systems, fully reaching even
sensitive targets such as the brain and retina....

The amount of label recovered in tissue components was quite high in all the
groups, but especially in the NA rats. In them, the liver alone retained,
for a long time, more than 2 % of the methanol carbon given in a single oral
dose of aspartame, and the rest of the body stored an additional 2 % or
more. These are indeed extremely high levels for adducts of formaldehyde, a
substance responsible of chronic deleterious effects (33), that has also
been considered carcinogenic (34,47).  The repeated occurrence of claims
that aspartame produces headache and other neurological and psychological
secondary effects-- more often than not challenged by careful analysis--
(5,9,10,15,48) may eventually find at least a partial explanation in the
permanence of the formaldehyde label, since formaldehyde intoxication can
induce similar effects (49).

The cumulative effects derived from the incorporation of label in the
chronic administration model suggests that regular intake of aspartame may
result in the progressive accumulation of formaldehyde adducts. It may be
further speculated that the formation of adducts can help to explain the
chronic effects aspartame consumption may induce on sensitive tissues such
as brain (6,9,19,50).  In any case, the possible negative effects that the
accumulation of formaldehyde adducts can induce is, obviously, long-term.
The alteration of protein integrity and function may needs some time to
induce substantial effects.  The damage to nucleic acids, mainly to DNA, may
eventually induce cell death and/or mutations. The results presented suggest
that the conversion of aspartame methanol into formaldehyde adducts in
significant amounts in vivo should to be taken into account because of the
widespread utilization of this sweetener. Further epidemiological and
long-term studies are needed to determine the extent of the hazard that
aspartame consumption poses for  humans."

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ].  Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte in (Appendix G). ]
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@...    919-684-3303, 660-5657

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall

Subject:  Re: Murray: Butchko:
Tephly: critique of Trocho report Apr 2002 8.29.2
     Date:   Fri, 30 Aug 2002 09:49:56 +0200
    From:   Marià Alemany <alemany@...>
        To:   "Rich Murray" <rmforall@...>
  References:  1

Dear Rich,

Thank you for the opportunity to say something about the "paper" by Tephly
that followed our study on the incorporation of aspartame-derived methanol
label into DNA and protein of rats.
I don't know if responding to that publication is worth the effort.

Surprisingly, a serious journal, such as Life Sciences published a rebuttal
of our previous paper as a normal "research paper", but including no new
information neither experimental work.  This is only a sample of the
"scientific" power of the advocates of aspartame.

Anybody can extract conclusions from this anomaly, but it seems to me that
there was nothing new in that pamphlet that may add information to what we
already explained in our paper. The responses to the questions raised by
Tephly are already in our paper, which means that either that it was not
read or, worst, it was misread.

The presence of aspartame-derived label in DNA and protein adducts is
unquestionable and unquestioned, and agrees with previous studies.
Then, what importance has the mechanism of incorporation? There were
adducts, and they represent loss of function and mutation.  That was our
thesis.

The reference to previous studies showing very low levels of formaldehyde in
blood do not refute our data.
First of all, measuring formaldehyde is tricky,
and in any case, the circulating levels would be below the current limit of
detection for most of the methods used.  That is the current explanation for
the low levels of methanol in plasma after aspartame loading: they are zero,
using most of the methods available for methanol, since the expected levels
are currently below the limit of detection...

In addition, it is not logical to expect to find measurable levels of
formaldehyde in a medium (blood) containing a huge amount of protein.
Formaldehyde reacts immediately with proteins because it is highly reactive:
that is the reason why we have found it in cell protein and DNA. It is
absurd to expect it to forfeit binding with cell proteins and go all the way
into the bloodstream!   Remember that formaldehyde is used to preserve
corpses precisely because it binds protein (including  those of putrefactive
bacteria) and prevents its degradation.

The "alternative" point expressed by Tephly, suggesting that aspartame
methanol-label goes all the way into formic acid and the C1 pathway was
thoroughly refuted by us, using experimental data.   There was no labelled
methionine nor thymine in protein and DNA respectively in the rat protein we
recovered from rats treated with aspartame. This means--unequivocally-- that
the label present in DNA and protein adducts was NOT incorporated into amino

acids or nucleic acid bases.  The only explanation for our data was that the
label was in the form of formaldehyde adducts.

If this explanation does not satisfy other scientists, they are free to
repeat the experiment and show where we went wrong, or to probe and prove
experimentally their hypotheses.

Otherwise, our results stand unchecked and, consequently, should be deemed
true.

I hope that this information will help any attentive reader understand why
we have left for good this field of study.

Best regards.
------------------------------
Prof.Dr. Marià Alemany
Grup de Recerca Nitrogen-Obesitat
Departament de Nutrició i Bromatologia
Facultat de Biologia, Universitat de Barcelona
Av. Diagonal, 645;  08028 Barcelona      Espanya/España/Spain
tel.  +34 93 403 4606;  fax:  +34 93 403 7064; E-mail: alemany@...

Life Sci 1999;  65(13):  PL157-60.  [ letter, usually not peer reviewed ]
Comments on the purported generation of formaldehyde and adduct
formation from the sweetener aspartame.
Tephly TR   Thomas R. Tephly  319-335-7979  thomas-tephly@...
ttephly@...   Department of Pharmacology
The University of Iowa, Iowa City 52242, USA.

A recent paper by Trocho et al. (1) describes experiments meant to
show that formaldehyde adducts are formed when rats are administered
the sweetener aspartame.
These authors assume that the methanol carbon of aspartame generates
formaldehyde which then forms adducts with protein, DNA, and RNA.
Doses employed range widely.
In this letter, studies which have been published previously and which were
not cited by these authors are reviewed in order to put into perspective the
disposition of methanol and formaldehyde in monkeys and humans, species
relevant to the toxicity of methanol and its toxic metabolite, formic acid.
PMID: 10503962, UI: 99431287

[ A number of pro-aspartame studies by Tephly and associates, invariably
funded by the aspartame industry (Monsanto, NutraSweet)  are criticized in
detail at:

"Scientific Abuse in Aspartame Research"
http://www.holisticmed.com/aspartame/abuse/methanol.html
Aspartame Toxicity Information Center    Mark D. Gold
www.HolisticMed.com/aspartame  603-225-2100
mgold@...  12 East Side Drive #2-18 Concord, NH 03301

Gold points out that industry methanol assays were too insensitive to
properly measure blood methanol levels.

http://groups.yahoo.com/group/aspartameNM/message/34
Davoli: aspartame causes rise in blood methanol 1986: Mario Negri
Institute for Pharmacological Research: Murray 10.30.99 rmforall

[selection]
Davoli, E., Cappellini L, Airoldi L, Fanelli R, 1986.
"Serum Methanol Concentrations in Rats and in Men
After a Single Dose of Aspartame,"
Food and Chemical Toxicology, Volume 24, No. 3, page 187-189.

Abstract:
Serum methanol concentrations were measured in rats and in humans
given oral aspartame.
The dose given to rats was the FDA's projected 99th percentile daily intake
for humans, assuming aspartame were to replace all sucrose sweeteners in the
diet (34 mg/kg).
Four male adult volunteers each received 500 mg, equivalent to 6-8.7 mg/kg,
which is approximately the FDA's estimate of mean daily human consumption.
Both treatments caused a rise in serum methanol.
In rats the mean peak value was 3.1 mg/litre 1 hr after administration;
serum methanol returned to endogenous values 4 hr after treatment.
In the men, the mean rise over endogenous values was 1.06 mg/litre after 45
min.
Two hours after treatment, serum methanol had returned to basal levels.
The temporary serum methanol increase showed peak values within the range of
individual basal levels. PMID: 3957170, UI: 86166135
Enrico Davoli has 22 citations in PubMed.

Regulatory Toxicology and Pharmacology 35, S1-S93 (2002)
doi:10.1006/rtph.2002.1542, available online at
http://www.idealibrary.com  $ 35.00
Aspartame: Review of Safety
page S1  0273-2300/02 $35.00
C 2002 Elsevier Science (USA)  All rights reserved.

Harriett H. Butchko 1
Medical and Scientific Affairs, The NutraSweet Company,
Mt. Prospect, Illinois
1 To whom correspondence should be addressed at Medical and Scientific
Affairs, The NutraSweet Company, 699 Wheeling Road, Mt.
Prospect, IL 60056. Fax: (847) 463-1755. harriett.h.butchko@....
W. Wayne Stargel
Research and Development, The NutraSweet Company,
Mt. Prospect, Illinois
C. Phil Comer
Graystone Associates, Inc., Macon, Georgia
Dale A. Mayhew
Regulatory Affairs, The NutraSweet Company, Mt. Prospect, Illinois
Christian Benninger (EEGs and Cognitive Function in PKU Heterozygotes)
Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
George L. Blackburn (Appetite, Food Intake, and Weight Control)
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, Massachusetts
Leo M. J. de Sonneville (Neuropsychological Function and Phenylalanine)
Departments of Pediatrics and Neurology, Vrije Universiteit, Medical
Center, Amsterdam, The Netherlands
Raif S. Geha (Allergy)
Division of Immunology, The Children's Hospital, Harvard Medical School,
Boston, Massachusetts
Zsolt Hertelendy (Liver Disease)
Division of Pharmaceutical Sciences, College of Pharmacy, University of
Cincinnati, Cincinnati, Ohio
Adalbert Koestner (Brain Tumors)
Department of Veterinary Biosciences, Ohio State University School of
Veterinary Medicine, Columbus, Ohio
Arthur S. Leon (Long-Term Safety in Humans)
Division of Kinesiology, College of Education and Human Development and
Department of Medicine, The Medical School,
University of Minnesota, Minneapolis, Minnesota
George U. Liepa (Renal Disease)
Department of Human, Environmental, and Consumer Resources, Eastern
Michigan University, Ypsilanti, Michigan
Kenneth E. McMartin (Methanol)
Department of Pharmacology and Therapeutics, Louisiana State University
Medical Center, Shreveport, Louisiana
Charles L. Mendenhall (Liver Disease)
Digestive Diseases Section, Department of Veterans Affairs Medical
Center, Cincinnati, Ohio
Ian C. Munro (Preface)
Cantox Health Sciences, Inc., Mississauga, Ontario, Canada
Edward J. Novotny (Seizures and EEGs)
Department of Pediatrics and Neurology, Yale University School of
Medicine, New Haven, Connecticut
Andrew G. Renwick (Preface)
Department of Pharmacology, University of Southampton, Southampton,
United Kingdom
Susan S. Schiffman (Headaches)
Department of Psychiatry, Duke University Medical Center, Durham, North
Carolina
Donald L. Schomer (Neurochemistry, Seizures and EEGs, Behavior,
Cognitive Function, and Mood)
Department of Neurology, Division of Neurophysiology and Epilepsy, Beth
Israel Deaconess Medical Center,
Harvard Medical School, Boston, Massachusetts
Bennett A. Shaywitz (Behavior, Cognitive Function, Mood in Children,
Seizures, and EEGs)
Departments of Pediatrics, Neurology, and Child Study, Yale University
School of Medicine, New Haven, Connecticut
Paul A. Spiers (Behavior, Cognition, and Mood)
Department of Psychiatry, Boston University School of Medicine, and
Clinical Research Center,
Massachusetts Institute of Technology, Boston, Massachusetts
Thomas R. Tephly (Methanol)
Department of Pharmacology, The University of Iowa, Iowa City, Iowa
John A. Thomas (Metabolism and Endocrine)
Department of Pharmacology, The University of Texas Health Science
Center at San Antonio, San Antonio, Texas
Friedrich K. Trefz (Phenylketonuria)
Department of Pediatrics, Children's Hospital of Reutlingen, University
of Tubingen, Reutlingen, Germany
Received January 8, 2002

DEDICATION
The authors dedicate this supplement to the memories of Lewis D.
Stegink, Ph.D., and L. J. Filer, Jr., M.D., Ph.D., from the University of
Iowa. Their early research on aspartame metabolism in humans formed the
basis for
much of the future research on aspartame that is discussed in this
supplement. Their objectivity and long-standing dedication to science as
well as their medical and scientific expertise are greatly missed.

pages S36 to S41 of S1 to S93
Safety of Methanol from Aspartame and the Diet

[Thomas R. Tephly (Methanol)   thomas-tephly@...
Department of Pharmacology, The University of Iowa, Iowa City, Iowa

Kenneth E. McMartin (Methanol)   kmcmar@...
Department of Pharmacology and Therapeutics, Louisiana State University]

page S39 [Extract]
Evaluation of Recent Issues Regarding Methanol Safety from Aspartame

Trocho et al. (1998) concluded from a study in rats that aspartame may be
hazardous because formaldehyde adducts from aspartame may accumulate in
tissue proteins and nucleic acids.
However, according to Tephly (1999), the dose of aspartame used in the study
  (20 mg/kg body wt =2 mg of methanol/kg body wt) would not yield blood
methanol concentrations outside control values.
Further, the administration of aspartame at 200 mg/kg body wt (equal to that
in a single bolus of about 25 liters of beverage sweetened 100% with
aspartame) to adult humans results in no detectable increase in blood
formate concentrations (Stegink et al., 1981).
Administration of  [14 C] methanol itself at 3000 mg/kg body wt to monkeys
produces no detectable [14 C] formaldehyde in body fluids and tissues
(McMartin et al., 1979), while there is ample accumulation of formate.
An alternative explanation for tissue incorporation of label from [14 C]
aspartame as described by Trocho et al. (1998) would be incorporation into
amino acids and nucleotides via one-carbon moieties from the
folate-dependent metabolism of formate.
The lack of formaldehyde accumulation at very high doses of methanol
questions considerably the conclusion that formaldehyde adducts are forming
from low doses of methanol (derived from high doses aspartame).
Thus, Tephly (1999) concluded, "the normal flux of one-carbon moieties
whether derived from pectin, aspartame, or fruit juices is a physiologic
phenomenon and not a toxic event."  (Next, Appendix F critiques the McMartin
study.) ]

Marià Alemany <alemany@...>,
Thomas R. Tephly <thomas-tephly@...>,
Kenneth E. McMartin <kmcmar@...>,
Harriett H. Butchko <harriett.h.butchko@...>,
Susan S. Schiffman <sss@...>,
Arthur S. Leon <leonx002@...>,
Christian Benninger <Christian_Benninger@...>,
George L. Blackburn <gblackbu@...>,
Leo M.J. de Sonneville <lmj.sonneville@...>,
Raif S. Geha <raif.geha@...>,
Edward J. Novotny, Jr. <edward.novotny@...>,
Andrew G. Renwick <agr@...>,
Donald L. Schomer <dschomer@...>,
Bennett A. Shaywitz <bennett.shaywitz@...>
************************************************************

Appendix F:

The exponential fragmentation of science into a fractile structure of ever
more atomized specialties ensures that every expert is a layman outside his
own specialty.

Capable laymen play an essential role by summarizing and integrating
scattered lines of inquiry that certain vested interests have long-term
campaigns for obscuring, since outright opposition would tend to attract
discussion and scrutiny that would soon vitiate billion dollar products.
Most professionals simply do not have the free time to investigate such
arcane, but possibly crucial, details.   Capable laymen now join together on
the Net to establish credibility by common sense,  polite mobilization of
specialized research, backed by support from informed specialists.  For
instance, I started investigating aspartame in early January 1999 and within
two months was being given papers by Woodrow C. Monte and Ralph G.Walton.

The route of aspartame to methanol to formaldehyde to formic acid is a
classic example.   Were this line of inquiry already suspected to be sure to
establish the harmlessness of aspartame, then the industry would have every
motive to spend a few paltry millions to both complete the research in
humans and widely publicize the results.

The fact that on the contrary, there is no industry funded research in
humans at all in the public domain on the specific biochemical and tissue
outcomes of formaldehyde and formic acid from aspartame leads to a
reasonable surmise that the industry has reason to fear, obscure, and derail
this inquiry.  Following the crooked but unmistakable trail of missing
research, i.e., avoided, ignored, misstated, discounted, obscured, explained
away, or simply never mentioned, is an excellent strategy for uncovering the
lurking secret.

In spring 1999, an eminent pro-aspartame scientist Christian Tschanz had
NutraSweet Co. give me their $ 130 review text of their research, "The
Clinical Evaluation of a Food Additive: Assessment of Aspartame" (1996), by
Christian Tschanz, Harriett H. Butchko, W. Wayne Stargel, and Frank N.
Kotsonis, all apartame stalwarts.

Chapter 5: "Metabolism and Pharmacokinetics of Radiolabeled Aspartame in
Normal Subjects", by Aziz Karim and Thomas Burns, has 10 pages and 10
citations. Page 63, Figure 4, Metabolic products derived from aspartame,
beta-aspartame, and DKP, does not list formaldehyde or formic acid.

The tangle of black arrows includes two paths from Aspartame to Methanol to
"CO2 + Body Constituents".   Now, that's pretty good public relations spin,
eh?  "Body Constituents", indeed?  This is systematic and persistent deceit,
as pernicious as it is profitable.  Aziz Karim, PhD is a "Distinguished
Research Fellow and Sr. Director, Clinical Research, G.D. Searle and
Company, Skokie, Illinois", where Thomas Burns, M.S. is a "Clinical Research
Manager".

They state that "in monkeys" with methanol or aspartame labelled in the
methyl ester, both with 14C, "...excretion of 14CO2 in the expired air
occured to the same extent (about 70% of the 14C dose) with both compounds,
indicating complete hydrolysis of the methyl ester moiety of aspartame
(Figure 6)."  They said nothing about resulting levels in blood plasma,
urine, feces, or any body tissues.   This is the typical commission by
omission strategy of industry research on aspartame.

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680

They found that about 70% of the radioactive methanol in aspartame put into
the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours, with little
additional elimination afterwards,  as carbon dioxide in exhaled air and in
the urine.  They did not mention that this meant that about 30% of the
methanol must transform into formaldehyde and then into formic acid, both of
which must remain as toxic products in all parts of the body.  They did not
report any studies on the distribution of radioactivity in body tissues, nor
give the absolute levels  for declining blood plasma proteins.  This study
did not monitor long-term use of aspartame, which might reveal cumulative
effects.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000 mg/kg,
67,000 mmol/kg, used by McMartin (1979).  Two L daily use of diet soda
provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose of 67
mmole/kg, a thousand times more than the dose in this study.

By eight hours excretion of the dose in air and urine had leveled off at
67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine, so 68.7
% was excreted, and 31.3% was retained. [This data is the average of 4
monkeys.]
  "...the 14C in the feces was negligible."
"That fraction not so excreted (about 31%) was converted to body
constituents through the one-carbon metabolic pool."

"All radioactivity measurements were counted to +-1% accuracy..."
This indicates that the results could not be claimed to have a precision of
a tenth of a percent.  OK, so this is a nit-pick-- but I believe espousing
spurious accuracy is a sign of scientific insecurity.

The abstract ends, "It was concluded that aspartame was digested to its
three constituents that were then absorbed as natural constituents of the
diet."
Thus, the concept is very subtly insinuated that methanol, as a constituent
of aspartame, is absorbed as a natural constituent of the diet.  "Dietary
methanol is derived in large part from fresh fruits and vetetables."
Nowhere in this report, or in the book chapter are mentioned the dread
words, "formaldehyde" and "formic acid".

Woodrow C. Monte, a Professor of Food Science at Arizona State University in
Tempe, drew completely opposite conclusions in his seminal review in 1984.
(Appendix G)

The same three reserchers, plus F.G. McMahon of Tulane University Medical
School, published a follow-up study, "Comparative metabolism of aspartame in
experimental animals and humans", J. Toxicology and Environmental Health 2:
441-451, 1976.

The abstract says, "Hydrolysis of the methyl group by intestinal esterases
yielded methanol, which was oxidized in the one-carbon metabolic pool to
CO2."

"The hypothetical pathways of metabolism, which aspartame was expected to
follow, are diagrammed in Fig. 1....The principle used to test the validity
of this hypothetical description of the metabolism of aspartame..."

Figure 1. shows in an nice orderly sequence that:
(a) MeOH --->  one-carbon metabolic pool --->  CO2 +  formyl metabolites .

Meanwhile, this sentence jumps from p. 441 to 442 under Figure 1., "The
absorbed methanol would be incorporated into the one-carbon pool and would
be converted [ page jump in sentence ] primarily to CO2 (Makar et.al., 1968;
Tephly et al, 1964), although a small fraction might be incorporated into
body constituents."

The graphs present the same methanol in monkey data as in 1973, but the
nowhere is the specific percentage of exhaled CO2 mentioned.   Methanol and
aspartame were also given to a few [ unspecified ] number of rats: "The
major fraction of the 14C was excreted in the expired air (Fig. 2)...Plasma
levels of 14C reached a peak [ absolute data not given ] at about 3 hr..."

In this follow-up report, for methanol and the methyl group in aspartame,
excretion in urine and feces were not mentioned in either the former monkey
or the new rat studies, the absolute plasma levels were not given, and, of
course, no measures were taken of 14C in body tissues.  The only hint of the
possible role of formaldehyde and formic acid was the rather diffident term
"formyl metabolites" in Figure 1.  Overall, we see consistent patterns of
avoiding any focus on the actual disposition of extremely  toxic
formaldehyde and formic acid, both persistent and cumulative, products in
body tissues.   Subtle equivocation and qualification was expressed by such
words as "hypothetical", "was expected to follow", "would be", "primarily",
"although a small fraction might be incorporated into body constituents",
"major fraction".

Methanol from aspartame was not studied in the other species: rabbits, dogs,
and humans.

It pays to investigate early studies, because then the coverup was less well
organized, more patchy.   The loosely organized world-wide exponential
growth of science ensures that the line of inquiry of methanol to
formaldehyde and formic acid will pop up here and there, but no one is
encouraged to make the connection with aspartame, widely proclaimed as "the
most thoroughly tested food additive in history"-- until the momentous,
unheralded Trocho study established explosive results in June 1998.
(Appendix E)

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from 11% methanol in aspartame:
Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

Life Sci 1991; 48(11): 1031-41. The toxicity of methanol. Tephly TR.
Department of Pharmacology, University of Iowa, Iowa City 52242.

"Abstract:
Methanol toxicity in humans and monkeys is characterized by a latent period
of many hours followed by a metabolic acidosis and ocular toxicity.
This is not observed in most lower animals.
The metabolic acidosis and blindness is apparently due to formic acid
accumulation in humans and monkeys, a feature not seen in lower animals.
The accumulation of formate is due to a deficiency in formate metabolism
which is, in turn, related, in part, to low hepatic tetrahydrofolate (H4
folate).
An excellent correlation between hepatic H4 folate and formate oxidation
rates has been shown within and across species.
Thus, humans and monkeys possess low hepatic H4 folate levels, low rates of
formate oxidation and accumulation of formate after methanol.
Formate, itself, produces blindness in monkeys in the absence of metabolic
acidosis.
In addition to low hepatic H4 folate concentrations, monkeys and humans
also have low hepatic 10-formyl H4 folate dehydrogenase levels, the enzyme
which is the ultimate catalyst for conversion of formate to carbon dioxide.
This review presents the basis for the role of folic acid-dependent
reactions in the regulation of methanol toxicity.
Publication Types:  Review   Review, Academic    PMID: 1997785"

p. 1035 "In the past, formaldehyde has often been suggested as the methanol
metabolite which produces toxicity (34,35).  Today, a great deal of
information is available concerning its lack of such a role.  The presence
of elevated formaldehyde levels in body fluids or tissues following methanol
administration has not been observed.  No formaldehyde has been detected in
blood, urine or tissues obtained from methanol-treated animals (36,37) and,
in methanol-poisoned humans, formaldehyde increases have not been
observed....
About 85% of a low dose of 14C-formaldehyde [radioactive label] is
excreted as pulmonary 14CO2 (49,50)....."

[  This suggests that 15% of the formaldehyde is indeed retained in the
body, a very significant result, considering its extreme and complex
toxicity.  ]

49. W.B. Neely, Biochem. Pharmacol. 13: 1137-1142 (1964).

50.  Xenobiotica 1982 Feb; 12(2): 119-24.
Formaldehyde metabolism by the rat: a re-appraisal.
Mashford PM, Jones AR.

1. The metabolism of [14C]formaldehyde has been investigated in the male
Sprague-Dawley rat.
It is extensively oxidized to CO2 and formate, which is excreted in the
urine.
2. Two radioactive compounds isolated from the urine of rats dosed with
[14C]formaldehyde have been identified as N-(hydroxymethyl)urea and
N,N'-bis-(hydroxymethyl)urea, and shown to be urinary artefacts.
3. Previous studies of the metabolism of formaldehyde by rats have been
re-appraised.
Differences in the rate of oxidation of formaldehyde in various strains of
rats result in the excretion of different urinary metabolites and, in some
cases, formaldehyde.
Excretion of formaldehyde leads to the formation of several artefacts
depending on the components present in the urine.   PMID: 6806997

Biochemical Pharmcacology 1979: 28; 645-649.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Kenneth E. McMartin, Gladys Martin-Amat, Patricia E. Noker
and Thomas R. Tephly
The Toxicology Center, Dept. of Pharmacology,
University of Iowa, Iowa City, Iowa 52242
K.E. McMartin and T.R. Tephly, authors of many pro-aspartame studies, in
Biochemical Pharmacology (1979) remarked, "It is now generally accepted
that the toxicity of methanol is due to the formation of toxic metabolites,
either formaldehyde or formic acid."  They put damage doses of methanol
into the stomachs of three monkeys, and, using insensitive tests, found no
formaldehyde in many tissues-- except for a single datum in the midbrain,
1.5 times the detection limit.  They did report  widespread accumulation of
formic acid in five tissues. The use of inadequate tests is common in
industry research that is funded to claim the safety of profitable toxins.
Since then, industry scientists have been very wary of doing studies on
primates, which all too easily show the dangers to humans.

"Abstract [ not given in PubMed ]:  [ My briefer comments are in square
brackets. ]
Methanol was administered [ by nasogastric tube ] either to untreated
cynomolgus monkeys [ 2-3.5 kg ] or to a folate-deficient cynomolgus monkey
which exhibits exceptional sensitivity to the toxic effects of methanol.
Marked formic acid accumulation in the blood and in body fluids and tissues
was observed.
No formaldehyde accumulation was observed in the blood and no formaldehyde
was detected in the urine, cerebrospinal fluid, vitreous humor, liver,
kidney, optic nerve, and brain in these monkeys at a time when marked
metabolic acidosis and other characteristics of methanol poisoning were
observed.
Following intravenous infusion into the monkey, formaldehyde was rapidly
eliminated from the blood with a half-life of about 1.5 min and formic acid
levels promptly increased in the blood.
Since formic acid accumulation accounted for the metabolic acidosis and
since ocular toxicity essentially identical to that produced in methanol
poisoning has been described after formate treatment, the predominant role
of formic acid as the major metabolic agent for methanol toxicity is
certified.
Also, results suggest that formaldehyde is not a major factor in the toxic
syndrome produced by methanol in the monkey."

"It is now generally accepted that the toxicity of methanol is due to the
formation of toxic metabolites (1,2), either formaldehyde or formic acid."

So, this is an acute toxicity study, with little relevance for chronic
long-term, low-level exposure.

Monkeys, like people, are susceptible to methanol toxicity.

This team cites their six previous methanol in monkey studies, from 1975 to
1977.

The report is difficult to understand, since the three monkeys were treated
differently, and different assays were used.

For the methanol sensitive, folate-deficient monkey A, the  assay used was
the chromatropic acid method, with a detection limit  of .025 mmol/L.   None
of the five tissues showed any formaldehyde with this assay, except the
midbrain, 0.14 mmol/kg wet weight tissue [ units converted from their 0.14
micromole/gm ]-- just 1.5 times the detection limit of .09 mmol/kg wet
tissue weight (given on p. 648).
[ Since 1 kg of water is 1 L, 1 mmol/kg is equivalent to 1 mmol/L. ]

Meanwhile, in the methanol sensitive, folate-deficient monkey A, the blood
formate level rose by 18 hours from  0.18 to 10.02 mEq/L.  [ I assume that a
mEq is equivalent to a mmol-- let me know if I'm wrong. ]  The formate
detection limits for the assays were not given in this report.  The formate
level in the vitreous humor of the eye of monkey A was 7.90 mEq/L.  It is
well known that formate is extremely damaging to the eye.  For unexplained
reasons, formate levels in the five tissues and cerebrospinal fluid were not
measured in the methanol sensitive, folate-deficient monkey A., in the
cerebrospinal fluid of monkey B,  or in the optic nerve of monkey C.
Formaldehyde was not measured in the optic nerve of Monkey A.  The kidney
formate level for monkey B was 6.33 and for C was only 0.44, with no comment
or explanation given.

The experiment seems arbitrary, capricious, and erratic.

For monkey A, after 18 hours, the urine formaldehyde level was below
detection level, while urine formate was 115.80 mEq/L--  so much of the
formaldehyde had been converted into formic acid, another cumulative, potent
toxin.

"In the presence of high formate values and definitive evidence of toxicity
in methanol-poisoned monkeys, no measurable formaldehyde was found in the
body tissues that were tested."

It is reasonable to surmise that more sensitive assays would have found
formaldehyde and formate bound to and reacted with a variety of cellular
substances in all tissues-- just as the 1998 Trocho study confirmed.
(Appendix E)

Monkeys B and C were normal, not extra vulnerable to methanol, and were
given 3,000 mg/kg methanol, and samples taken at 18 hr.   Formaldehyde was
detected only in the blood of Monkey B, while formate was found in 8 and 10,
respectively, of the 10 fluid and tissue samples in Monkeys B and C.  For
instance, the lowest value of formate, except for zero-time blood, for each
monkey was in the midbrain, 2.16 mmol/kg for Monkey B (24 times the
detection limit for the chromatropic acid method) and 1.02 mmol/kg (1.3
times the detection for the dimedon method) for Monkey C.  This shows
accumulation of formate in liver, kidney, optic nerve, cerebrum, and
midbrain.

"Thus, whereas one can associate formate intimately with ocular toxicity in
the monkey, no association of formaldehyde with ocular toxicity can be made
at this time.  It is not possible to completely eliminate formaldehyde as a
toxic intermediate because formaldehyde could be formed slowly within cells
and interfere with normal cellular function without ever obtaining levels
that were detectable in body fluids..."

"Acknowledgements-- This research was supported by NIH grant GM 19420
and GM 12675."  [not funded by the industry]

Often, pro-aspartame studies have titles and summaries that are not
supported by a close study of the details:
http://groups.yahoo.com/group/aspartameNM/message/891
flawed test for aspartame DNA damage: Jeffrey & Williams 2000:
Murray: 11.20.2 rmforall
************************************************************

Appendix G:

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall

Dr. Woodrow C. Monte  Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984;  36 (1):  42-54.
(62 references)   Professsor of Food Science [retired 1992]
Arizona State University,  Tempe, Arizona 85287  woodymonte@...
[ Summary: The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame.  The EPA limit for water is 7.8 mg daily
for methanol (wood alcohol), a deadly cumulative poison. Many users
drink 1-2 L daily. The reported symptoms are entirely consistent
with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but,
like all juices, has 16 times more ethanol, which strongly protects
against methanol.) ]

"Fruit and vegetables contain pectin with variable methyl ester content.
However, the human has no digestive enzymes for pectin (6, 25)
particularly the pectin esterase required for its hydrolysis to methanol
(26).

Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3).  In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6)  (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120 deg C produced
only traces of methanol (3).  Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).  Entrapment of these
volatiles probably accounts for the elevation in methanol levels of certain
fruits and vegetable products during canning (31, 33)."

"The scientific literature indicates that a fair estimate of methanol
content of commonly consumed fruit juices is on the order of 40 parts
per million (Table 1).  Stegink, et al. points out that some neutral
spirits contain as much as 1.5 grams/liter of methanol (51);
what is not mentioned is the fact that if these spirits are at least 60
proof (30% ethanol) this still represents the presence of over 200
molecules of ethanol for every molecule of methanol that is digested.

An exhaustive search of the present literature indicates that no testing of
natural substances has ever shown methanol appearing alone; in
every case ethanol is also present, usually, in much higher
concentrations (15, 27, 28, 30, 31, 35, 44, 45).

Fresh orange juices can have very little methanol (0.8 mg/liter), and
have a concomitant ethyl alcohol content of 380 mg/liter (28)."

"-- Data obtained in a Department of Agriculture survey of the food intake
of a statistically sampled group of over 17,000 consumers nationwide
(1), indicate that the 17.6% of the population that consume orange juice
daily take in an average of 185.5 gm of that juice. These statistics
indicate that 1.1% of the population consume an average of 173.9 gm of
grapefruit juice while only 1.8% drink approximately 201 gm of tomato
juice daily. Table 1 shows that under normal conditions these
individuals would only be expected to consume between 1 and 7 mg of
methanol a day from these sources. Even if an individual consumed two
juices in the same day or a more exotic juice such as black currant,
there would still be some protection afforded by the ethanol present in
these natural juices.

Consumption of aspartame sweetened drinks at
levels commonly used to replace lost fluid during exercise yields
methanol intake between 15 and 100 times these normal intakes (Table 1).

This is comparable to that of "winos"
but without the metabolic reprieve afforded
by ethanol. An alcoholic consuming 1500 calories a day from
alcoholic sources alone may consume between 0 and 600 mg of methanol
each day depending on his choice of beverages (Table 1).

The consumption of aspartame sweetened soft drinks or other beverages
is not limited by either calories or osmolarity,
and can equal the daily water loss
of an individual (which for active people in a state like
Arizona can exceed 5 liters). The resultant daily methanol intake might
then rise to unprecedented levels.

Methanol is a cumulative toxin (8)
and for some clinical manifestations it may be a human-specific toxin."

Recent research [see links at end of post] supports his focus on the
methanol to formaldehyde toxic process:

"The United States Environmental Protection Agency in their Multimedia
Environmental Goals for Environmental Assessment recommends a minimum
acute toxicity concentration of methanol in drinking water at 3.9 parts
per million, with a recommended limit of consumption below 7.8 mg/day
(8). This report clearly indicates that methanol:

"...is considered a cumulative poison due to the low rate of excretion
once it is absorbed.  In the body, methanol is oxidized to formaldehyde
and formic acid; both of these metabolites are toxic." (8)...

Recently the toxic role of formaldehyde (in methanol toxicity) has been
questioned (34).  No skeptic can overlook the fact that, metabolically,
formaldehyde must be formed as an intermediate to formic acid
production (54).

Formaldehyde has a high reactivity which may be why it has not been
found in humans or other primates during methanol poisoning (59)....

If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave.

Formaldehyde is a known carcinogen (57) producing squanous-cell
carcinomas by inhalation exposure in experimental animals (22).  The
available epidemiological studies do not provide adequate data for
assessing the carcinogenicity of formaldehyde in man (22, 24, 57).

However, reaction of formaldehyde with deoxyribonucleic acid (DNA)
has resulted in irreversible denaturation that could interfere with DNA
replication and result in mutation (37)..."
************************************************************

Appendix  H:

http://www.dorway.com/tldaddic.html  5-page review    full text
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter  2000 Jan;  HJRobertsMD@...
http://www.sunsentpress.com/    sunsentpress@...
Sunshine Sentinel Press  P.O.Box 17799  West Palm Beach, FL 33416
800-814-9800 561-588-7628 561-547-8008 fax

http://groups.yahoo.com/group/aspartameNM/message/669
1038-page medical text   "Aspartame Disease: An Ignored Epidemic"
published May 30  2001    $ 60.00 postpaid    data from 1200 cases
available at  http://www.amazon.com
over 600 references from standard medical research

http://groups.yahoo.com/group/aspartameNM/message/790
RTM: Moseley:
review Roberts "Aspartame Disease: An Ignored Epidemic" 2.7.2  rmforall

http://groups.yahoo.com/group/aspartameNM/message/883
three texts by H.J. Roberts, 1958, 1971, 1979: Murray 11.6.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/880
Roberts 45 clinical research reports in mainstream journals:
Murray  10.20.2 rmforall

[ I found two cases reported that specificly described eyelid
dermatitis. ]
Aspartame Disease (2001), pages 330 to 370, Chapter VIII, Allergies and Skin
reactions: Immunologic Perspectives:
p. 337 "B. Itching and Hives:  In this series of 1,200 aspartame reactors,
87 (7 %) developed severe itching without a rash, 47 (4 %) hives, and 108 (9
%) other eruptions....As with other foods and additives, hives due to
ingesting aspartame products generally occurred within 6-12 hours....The
high incidence of such reactions among females (see above) is also
noteworthy."

p. 346  "Reports by Others:
In its initial monitoring of adverse reactions to aspartame, the FDA
received reports of 111 rashes and 80 cases of hives among 3,326 aspartame
complainants.
Tollefson, L., Barnard, R. J., Glinsmann, W. H.: Monitoring of adverse
reactions to aspartame reported to the U.S. Food and Drug Administration.
In, Proceedings of the First International Meeting on Dietary Phenylalanine
and Brain Function, edited by R. J. Wurtman and E. Ritter-Walker, Wash.,
D.C., May 8-10, 1987, 347-372.

Kulczycki (1986) initially described two patients with aspartame-induced
hives and angioedema.

[...Hives of the eyelids,...]

* "Hives of the eyelids, lips, hands, face and trunk, along with shortness
of breath and joint swelling, were precipitated by diet colas and an
aspartame table sweeetener in a 23-year-old female.  The causative role of
aspartame was confirmed by open challenge and by two double-blind challenges
using opaque capsules of aspartame or a placebo.  Itching and hives occurred
within one and a half to two hours after swallowing the aspartame.  Their
severity tended to correlate with the challenge dose (25 or 50 mg).  [A
12-0z can of diet soda gives 200 mg.]
*A 42-year-old woman developed hives and angioedema within one hour after
swallowing aspartame drinks.  They reoccured within 90 minutes after
challenge with 75 mg aspartame in a double-blind study.
Kulczycki A, Jr.:  Aspartame-induced urticaria. Annals of Internal Medicine
1986 Feb; 104(2): 207-208.   PMID: 3946947

Kulczycki (1987) subsequently reported an additional 224 patients who
contacted him for possible aspartame sensitivity; 154 had chronic hives,
angioedema or both.  Fifty of the first 75 refrained from ingesting
aspartame for two weeks, and noted complete resolution of their hives.  Of
these 50 patients, 22 reacted positively when rechallenged with aspartame.
Kulczycki, A., Jr.: Aspartame allergy. Allergy Observer 1987; June: 6.

Kulczycki, A., Jr.: Aspartame induced hives (Letter)  J. of Allergy and
Clinical Immunolology 1995 Feb; 95(2): 639-640.   PMID: 7852678
Comment on: J Allergy Clin Immunol. 1993 Oct; 92(4): 513-20.

Downham (1992) reported 23 patients with hypersensitivity skin reactions
attributable to drinking 12-72 ounces of aspartame sodas daily.  Twenty were
women.  Their reactions included urticaria (19), angioedema (2), macular
purpura (2), panniculitis (2), and eczematous dermatitis (1).  In each
instance, the reaction recurred after rechallenge with a diet soda, or
coffee/tea sweetened with an aspartame product.
Downham, T. F. II: Possible hypersensitivity reactions to aspartame.
Clinical Cases in Dermatology 1992; 4 (Number 4): 12-15."
[ Department of Dermatology, Henry Ford Hospital, Detroit, Mich, USA.

Thomas F. Downham, M.D. (1-800-436-7936)
Specialties: Dermatology
Locations:  Taylor
Board Certifications: American Board of Dermatology
American Board of Dermatology: Dermatopath
Medical School Education: University of Michigan Medical School
Post Graduate Training: Henry Ford Hospital - Internal Medicine
Wayne State University - Dermatology
Clinical and Special Medical Interests: General dermatology, drug eruptions,
bullous dermatoses, lupus erythematosus
The physician-patient relationship is sacred and is the key to quality
medical care.
Downham Dermatology, Henry Ford Medical Center-Taylor
24555 Haig Street  Taylor, MI 48180    313-375-2101  Fax: 313-375-2140
info@...
Thomas F. Downham II, MD  Chairman, Internet Committee
Michigan Dermatological Society   June 15, 2001  thomasd@.... ]


[ ... a painful violaceous rash of the eyelids... ]

p. 352  "Case VIII-E-2:  A 57-year-old medical secretary suffered aspartame
disease.  Many of her manifestations were previously diagnosed as systemic
lupus erythematosus.  She had been seen in consultation by an allergist, two
hematologists, two opthalmologists, a neurologist, an internist, an
endocrinologist and three dermatologists!  Repeat ANA titers were elevated
to 1:2,560 or higher.

She experienced pain in both eyes, marked photosensitivity (interfering with
her ability to drive or travel), dry eyes, loss of hearing in both ears,
unexplained facial pain, palpitations, pain of the tongue and lips, intense
thirst, a painful violaceous rash of the eyelids, other eruptions, and
thinning of the hair.  Various diagnostic procedures had been negative--
including skin biopsies of the lids and arms, a salivary gland biopsy, and
various antibody studies.

The patient was told about aspartame disease by her pharmacist-son.  Her
daily consumption included up to 12 packets of an aspartame tabletop
sweetener, one or two cans of diet cola, eight ounces or more of an
aspartame yogurt, and other aspartame products (cereal, gelatins, gum,
mints, juice cocktails).  Her eyes began to improve within several days
after avoiding aspartame products."

[ "Dry eyes, ocular irritation from contact lens, or both, occurred in 46
(8.3%) aspartame reactors, In addition to the sensation of local
discomfort and "sand" in the eyes, the eyelids of such patients tend
to become swollen and infected, at times with loss of eyelashes.

The causative or contributory role of aspartame was indicated by
these clear-cut clinical correlates: (1) prompt and gratifying
improvement of ocular and other symptoms following the cessation
of aspartame, generally within several days; and (2) their recurrence
shortly after resuming such products. This sequence predictably
recurred after rechallenge with aspartame, known or inadvertent."  ]

"DRY EYES" FROM USE OF ASPARTAME (NUTRASWEET):  [ full text ]
Associated Insights Concerning the Sjogren Syndrome
The Townsend Letter for Doctors, Jan. 1994, by H. J. Roberts,
M.D., FCCP, FACA.

"It is of use from time to time to take stock, so to speak of our
knowledge of a particular disease, to see exactly where we stand in
regard to it, to inquire what conclusions the accumulated facts seem
to point to, and to ascertain in what direction we may look for
fruitful investigations in the future." Sir William Osler

Abstract

"Dry eyes" and associated difficulty in wearing contact lenses were
prominent complaints offered by 56 (8.3%) of 551 aspartame
reactors. Xerostomia (dry mouth) was a frequent concomitant. The
symptoms promptly improved after they stopped
aspartame-containing products, and predictably recurred on
aspartame rechallenge. The concomitant joint pains, severe
confusion, memory loss and depression also have clinical
significance, with special reference to the Sjogren syndrome.

The cause and management of "dry eyes" challenge
ophthalmologists and primary care physicians. This symptom was
unexpectedly and repeatedly encountered among patients
manifesting other reactions to products containing aspartame, a
sweetener currently being consumed by 54% of adults in the United
States. This complaint was encountered in both the routine
questioning of apparent aspartame reactors and a computerized,
9-page survey of such individuals. Many also volunteered difficulty
in wearing contact lenses due to decreased tears, dry mouth
(xerostomia), joint pains, confusion and memory loss - all
specifically attributed to the use of aspartame products.

Methods

Data were obtained from 551 persons who appeared to have
systemic reactions to aspartame. They consisted of 160 private
patients or aspartame reactors who were personally interviewed, and
391 individuals who described their adverse side effects in the
survey questionnaire...including observations after rechallenge. The
names of the latter group were supplied by Aspartame Victims and
Their Friends (courtesy of Mrs. Shannon  Roth), the Community
Nutrition Institute (courtesy of Mr. Rod Leonard), and Dr.
Woodrow Monte of Arizona State University.

The completed questionnaires were analyzed with the assistance of
the Management Information System staff at the Good Samaritan
Hospital, West Palm Beach, Florida.

Results

Dry eyes, ocular irritation from contact lens, or both, occurred in 46
(8.3%) aspartame reactors, In addition to the sensation of local
discomfort and "sand" in the eyes, the eyelids of such patients tend
to become swollen and infected, at times with loss of eyelashes.

The causative or contributory role of aspartame was indicated by
these clear-cut clinical correlates: (1) prompt and gratifying
improvement of ocular and other symptoms following the cessation
of aspartame, generally within several days; and (2) their recurrence
shortly after resuming such products. This sequence predictably
recurred after rechallenge with aspartame, known or inadvertent.

These observations have been duplicated by more than a score of
patients complaining of dry eyes in subsequent aspartame reactors.
There were related problems. For example, a physician who
consumed considerable diet sodas developed a type of corneal
dystrophy generally associated with the chronic use of certain drugs
(e.g., indomethacin).

Computerized correlations between aspartame-associated dry eyes,
and "marked memory loss," "severe depression" and "severe mental
confusion" were done on the first 362 aspartame reactors who
completed the questionnaire. (There was a 30.8% response to the
initial mailing of 1,177 forms.) The correlates were as follows:

* Recent aspartame-associated dry eyes and severe depression - 18
(4.9%) * Recent aspartame-associated dry eyes and marked
memory loss - 20 (5.5%) * Recent aspartame-associated dry eyes
and severe mental confusion - 9 (2.4%)

Other complaints offered by the larger cohort had considerable
significance, with particular reference to the Sjogren syndrome.
They included excessive thirst due to dry mouth (xerostomia) in 65
(12%), and severe joint pains in 58 (11%). It is noteworthy that
three-fourths of patients in this and the large series of aspartame
reactors were women averaging 50 years, a phenomenon also
encountered in the Sjogren syndrome.

Representative Case Reports

Case 1 - A 47 year-old woman complained of severe dryness of the
eyes that required one bottle of artificial tears a week. Her
consumption of aspartame included 10-12 glasses or cups of
aspartame-sweetened beverages, the addition of a tabletop
sweetener to 3 cups of coffee in the morning, and considerable
aspartame pudding. She also suffered confusion, significant memory
loss, intense headaches (never previously a problem), impaired
hearing, lightheadedness, severe "nervousness," muscle cramps, and
depressions with suicidal thoughts. These symptoms markedly
improved after stopping aspartame, and disappeared within several
weeks. She no longer required artificial tears. Such dramatic
improvement enabled her to travel abroad several weeks later with
her church group for relief work.

Case 2 - A 36 year-old businesswoman complained of recent
difficulty wearing contact lenses. She had been consuming
considerable amounts of soft drinks and gum containing aspartame.
These and other symptoms - including lightheadedness, headache
and leg cramps - abated within two weeks after all aspartame
products were avoided.

Case 3 - a 61 year-old female court reporter developed dry eyes and
bilateral blurring of vision. Other recent complaints included marked
memory loss, severe headache, dizziness, extreme irritability, and
atypical facial and joint pains. As a result, she had been making
many errors at work. The patient improved "immediately" when she
ran out of aspartame-containing beverages, and resumed regular
sodas. She therefore deduced that aspartame products had been
causing her problems. Her previous daily consumption included 4
cans of aspartame soft drinks, 2 glasses of aspartame hot chocolate,
and 6 packets of an aspartame tabletop sweetener.

Comment

The unexpected associated of aspartame use and dry eyes offers
clues concerning this symptom and the Sjogren syndrome. Other
problems encountered in aspartame reactors, especially dry mouth
and joint pains provide related insights.

Two reactors who complained of "thick saliva" developed
enlargement and tenderness of the parotid glands. The secretory
structures of the salivary glands presumably had been affected by
aspartame, as well as the lacrimal glands. The affinity of aspartame
for salivary glands were demonstrated experimentally by the prompt
uptake of isotopically-labelled aspartame.

The Sjogren or sicca syndrome affects an estimated 2% of the adult
population. The reduction or absence of lacrimal and salivary
secretions results in dry eyes and dryness of the mouth. (The
diagnostic lipstick-on-teeth sign consists of lipstick adhering to the
upper front teeth). This disorder is presently regarding as a chronic
autoimmune disorder resulting from lymphocyte-mediated
destruction of these glands and changes in the points.

A vicious cycle is likely to ensue if considerable
aspartame-containing beverages are consumed because of the
intense thirst created by severe dryness of the mouth. Weiffenbach
et al. demonstrated that taste impairment is not a necessary
consequence of salivary gland dysfunction among patients with "dry
mouth" caused by the chronic absence of saliva. Accordingly, such
individuals may come to prefer the taste of aspartame in satisfying
their chronic thirst, with perpetuation of the sicca syndrome.

The systemic and central nervous system sequelae of the Sjogren
syndrome underscore the potential importance of these findings.
Cognitive impairment and lamenting features have been reported by
one-fourth of Sjogren patients. Severe confusion and memory loss
also were noted in 157 (28.5%) aspartame reactors in the present
series. Indeed, many reactors in their third and fourth decades
asked, "Could I be developing early Alzheimer's disease?" The
prompt and impressive regression of their confusion and memory
impairment after abstinence from aspartame proved reassuring.

Several phenomenon may explain cerebral dysfunction associated
with aspartame use. They include flooding of the brain with large
amounts of phenylalanine (50% of the aspartame molecule),
disturbances of neurotransmitters (especially dopamine), other
effects of its three chemical components (phenylalanine, aspartic
acid, methanol), methanol-induced cerebral edema, and glucopenia
due to increased insulin release and concomitant decreased food
intake in an attempt to lose weight.
************************************************************

Appendix I:

[ I have have not corrected text, typos, or spelling, except to assemble
longer lines.  Each of these cases describes major improvements within
weeks of giving up aspartame.  The varied symptoms are consistent with
chronic long-term low-dose formaldehyde toxicity ]

"...I had unexplained rashes, my hair started to fall out..."

TO: Rhonda and Randy  Rhockinrho@*****
FROM: bettym19@...
DATE: Sat, 14 Dec 2002 23:47:22 -0500
SUBJECT: Re: I'm a new person  Aspartame Disease  /Markle/World
Environmental Conference post

-0500, Rhockinrho@... wrote:
Dear Ms. Betty,

      Thank you for all your (and your friends) wonderful work.   I
firmly believe it saved my life.

       I was always a very active person, worked long hours, raised a
family and continued to follow my love of art.    I started drinking
Diet Coke in the early 80's when it came on the market, but in very
small quantities.  Over the years I started to have mood swings and
unexplained physical problems.  Doctors wrote it off as having had a
hysteretomy at an early age or the stress of being a single parent.

      In Aug. of 2000 I was injured at work and due to the nature of my
injury,  cronic pain in both wrists, I began to see a round of Doctors
trying to get a diagnosis.  In the mean time depression and anxiety
attacks started to take over my life.   I had also started drinking 6,
8 and sometimes more 12 oz. cans of Diet Coke.    I gained 30 pounds, on
my thin frame I looked bloated all the time.    I had unexplained
rashes, my hair started to fall out, memory loss, loss of focus ( I
could no longer read a book and remember what I had just read - I've
always been an avid reader and this was devastating).     My friends and
family started thinking that I was a cronic alcoholic due to my mood
swings and unpredictable behaivor.   At first they tried to help but
then began to avoid me.     My social life became going to doctors and
whoever happened to be on TV.  (Sometimes I would change the channel and
forget what I had just watched on the other channel)

      Doctors tested me for everything from Lupus and MS to having
several MRI and other types of scans.   The only thing they didn't test
me for was leprosy and I was begining to think that was next.

     I've only been married for 3 years (2nd time around) and I thank
God he is man he is .   He stuck by me and encouraged me to find an
answer when most men would have bailed out .   I was sick for 2 years of
our 3 year marraige, unable to perform even the most simple of  tasks.
He would work and then come home to cook dinner and do most of the
household chores.   I continued to go to doctors, both for my hands and
therapy for the depression.    I was diagnosed with everything from
Carpal Tunnel to faking it, one Dr. at Vanderbuilt went so far as to
call me a liar.   About 3 months ago I was told by a neurologist that I
had Accute Fibral Myalgia, the great dumping ground for "We don't know
what the heck it is".

      I prayed so hard for something that whould head me in the right
direction.   I was taking meds for the depression and panic attacks
then washing it down with Diet Coke.     Then one day out of the blue my
brother sent me the Markle letter .   That letter started me on the
path to finding you and the information I needed.   Then on to finding
my health, I'm still recovering and still have plenty of problems but
now I have hope, something I didn't have 3 months ago.   My entire
family has given up anything that says Sugar Free or Artificial
Sweetners.

     I have lost 20 of the 30 pounds I gained, 17 of them in the first 2
weeks!   My depression is under control for the most part but I'm still
fighting the panic attacks. After 20 years of partaking of something I
thought safe I'm sure it's going to be a long road back but at atleast
now I have a road map.     I still have good days and bad days but now
the good is way ahead!       My hands I'm afraid will probably never
recover fully as I have Peripheral Neuropathy, the outer coating of the
nerves in my wrists are worn off, due to the type of work I have
done.   But atleast I know I'm not going crazy and my quality of life
has improved dramatically.
      I don't know how to thank you and everyone else enough except to
spread the word.   And I'm doing that the old fashioned way, by talking
to everyone I possibly can.

      My husband made the comment to me when I finally discovered the
truth about this poison,   He said " I tried it once and it smelled
like embaling fluid, and I just could't drink it"    When Diet Coke
first came on the market  worked for a funeral home and was quite
familiar with the smell. We never put the two together until I found the
dorway site.  He too is  thankful for your information and giving him
his wife back.

       Keep up the good work and I will try to do the same on my end.

        Thank you  for giving us our life back.
With all Love and Respect,  Rhonda and Randy

P.S.     I just talked with my Aunt who's daughter is living with MS.
I have given her the web address but I'm also having lunch with her
tommorow and will continue the discussion.  I'm praying that my cousin
is atleast open to the idea.  If my talking, which I love to do, can
help one person, then I've accomplished something and all my pain was
worth it.

May the Angels be with you.
*********************

[ Wanda had a variety of eye, skin, and hair problems. ]

To: wlw <74218bjw@*****>
FROM: bettym19@...
DATE: Sun, 15 Dec 2002 04:38:50 -0500
SUBJECT: Aspartame Disease: Joint pain,  surgery effect, vertigo, etc.
(plus info on prolotherapy)

From: "wlw" <74218bjw@*****>
To: <bettym19@...>
Subject: Aspartame Poisoning (You are a God Send)
Date: Tue, 26 Nov 2002 19:56:18 -0600
X-Mailer: Microsoft Outlook Express 5.00.2615.200

Hello

First I would like to thank you for all the information on the web about
aspartame poisoning.  This is my story:

I have been sick for approximately the past six or seven years.  I have
gone to the doctor so many times that I have lost count.  Betty Martini
I can't thank you enough for the information on the web about Aspartame
Poisoning.  If not for this site I truly believe that in a year I would
have been crippled and I would have finally died.  I had lost my
spirit..my soul was leaving and I was beginning not to care.  I had lost
most of my faith in the medical system and in doctors.  I truly had lost
all faith in medication!!!!!!!! I truly have my own pharmacy here at
home!!!

About two months ago my health went spiraling down hill fast.  When I
truly think back I was progressively getting sick even before that.
These were my symptoms:

Headache...Blurred Vision...Dizziness....Constant Sinus problems to the
point where the doctor had given me an inhaler...(it had progressed to
wheezing)...eyes burring at times...coughing at times
uncontrollably..tired all the time...bouts with diarrhea...nauseated all
the time..stomach bloated...forgetfulness..rash...chills..fever...chills
where I would be shaking...weight gain....Heart Palpitations....Chest
Pain...Mentral Cramps from HELL had started to plaque me that lasted the
whole time with terrible headaches...Itching...Hunger...numbness in my
legs sometimes and my hands..fingers...my skin started to get dry and
cracked..acne was baddd...started getting bad spots on my face and
really dry skin....my skin started turning dark in areas.....my finger
nails changed colors...started splitting and grew out with ridges in
them from the nail beds...toe nails to same thing....heart beating
fast..ringing in my ears...numbness in my face and my ear... my gums
changing colors....from a brown (I'm African American) to a light dull
red or pink...rash on my back and chest...had to hold on to the
bannister and the wall to walk down the stairs...when I got up in the
mornings I couldn't stand straight up for about an hour...had to work my
way up to it....

I went from doctor to doctor..dermatologist to dermatologist...and back
giving medication and all sorts of things that didn't work....I even
order proactive and it didn't work either.....I had growths on my face
that resembled moles but wasn't moles some kind of acne I uess...skinned
started to get wrinkled and around my eyes was turning "dark" above and
below and wrinkly... I was scared and didn't know what the hell was
going on with my body and the doctors couldn't tell me.  I was having
hormonal symptoms to.

After awhile I stopped going to the doctor because all I got was
medicine that didn't work and I stop taking because it wasn't working
and I was losing faith in the medical system.  I had to go to the
emergency room because I was having the following symptoms some of which
I had had all along but got worse. I packed my bags and called two of my
friends to let them know because I truly thought I was going to have a
heart attack or a stroke.  Now these symptoms got progressively worse
because I went the second day to the emergency room.  These were my
symptoms:

Headache....dizziness.....pain in my body and joints...muscle spasms
(painful) ...the right side of my face was numb..my right ear..down my
neck right side and behind right side....heart beating fast....ringing
in my ears...speed up for a while then slow down the speed up out of the
blue...I could feel it. When I got in the examining room I ask for a
bottle to urinate in because I made sure I drank enough so I would have
to urinate.  The intern said she didn't think I would have to but I
insisted saying if the doctor doesn't need it then we can just throw it
away. She agreed.  After talking to an intern and the doctor (Dr
Sellers) and the doctor doing a bunch of manual test on me the emergency
room doctor diagnosed me with Vertigo and sent me home.  He gave me
something for nausea and dizziness (TIGAN and MECLIZINE).I asked alot of
questions but it just did not satisfy me because it didn't all fit.  I
got home and looked up Vertigo on the internet and all the symptoms did
not fit.  I knew something else was wrong or I needed to know what was
causing the vertigo.  I got so sick on the way home I had to pull over
to the side of the road for a little while before proceeding home.
Needless to say the medication did not work for I was still dizzy and
still nauseated.

Approximately three weeks later my health was spiraling down hill again
fast. I was scared but did not believe in the medical system anymore so
I didn't go to the hospital. Instead I just started to finally give up.
I had bad bad cramps in my stomach and stomach pain. I was
dizzy..blurred vision...slurred speech..body pain and just sick all
over.  I just prayed about it and gave it to god literally.  I told him
that I wasn't scared to die because my grandmother was up there and my
little dog.. my aunt and two uncles and a little cousin.  I just wanted
to know why.  Not why is this happening to me just why am I sick ....
what's the cause. Ms Martini I was really tired.  I had already
withdrawn from ALL my friends never answered my door if I heard
it...didn't answer the phone to much.  I guess I was depressed.  I had
mood swings and  just a overall attitude of why am I even here to keep
suffering like this and to make it worse  "with no explanation".  Then I
just laid down just to feel my heart beating sooooo fast and my head
hurting nauseated and running to the bathroom...chest pains..numbness in
my face again dizziness...so I got on the computer again and looked up
heart failure..diabetes...stroke...etc.

Then for some reason I just got mad and went in the bathroom and got
everything I use on my face...everything I bath with (all cosmetics)
everything that I eat and drink and brought it up here and put the
ingredients in this computer to look it all up.  It took me awhile but
when I got to my CRYSTAL LIGHT and got to aspartame it hit me like a ton
of breaks.  There it was POISON.  I was slowly poisoning myself to
death. I drank Crystal Light All The Time for Years.  I could not
believe it.  All this time being sick.  I had even made a comment to a
friend that if I didn't live by myself and cook my own food I would
swear that someone was poisoning me.  Little did I know I was poisoning
myself with the APPROVAL OF THE FDA.   Just sickening.  Then I cried and
I cried and I cried because I was mad I was sooo very angry and when I
thought about all the older people I see putting those little packets of
poison in their coffee and tea it just made me more angry.  I thought
about the kids who can't explain their symptoms and wonder do they even
care.  Children are so precious and should not be hurt in anyway and the
elderly is just as precious.  The should get old and die from old age
not from poison. Then the elderly would think they were just getting old
and getting sick like that was part of it. Then I thought about all the
people who don't know and I made a promise that I would tell EVERYONE I
know.  I started making phone calls to Kraft Foods who were on a
different time zone from me but of course they didn't call me back but I
got a confirmation number.  I went to their site and saw where people
asked about the phenylalaine and their answer was full of it.  I went to
slim fast and their answer was even WORSE.

I called NatraTaste which I forgot to tell you.  I went and bought some
Green Tea after the time that I went to the emergency room.  I was
sweetening it with sugar. I thought that sweetened it with sugar was
just defeating the purpose of why I'm drinking the green tea in the
first place.  I wanted to get some honey.  When I went to get the honey
the store was out so I went to Wal-Mart and found NatraTaste instead.  I
taste like sugar and even had almost the texture of sugar.  I made my
green tea and put about two of those in it because it was a oversized
tea cup. Well I got a headache when I drank it but at the time I didn't
know that was the cause.  I didn't put it together until after I read
your site.  NatraTaste contains 100% aspartame.  I sometimes got sugar
free jello and a few other sugar free or light things.  Sometimes chewed
sugar free gum or gum sweetened with aspartame.

About March I had to go to the dentist because I had a growth on my gums
and they were getting sore.  Now I truly believe it was caused by
aspartame usage.  I drank Crystal Light all the time.  I even took it to
work with me to keep me from going to the drink machine.  I would even
buy diet sprite or diet 7up and sometimes added it to the Crystal Light
unknowingly to me making myself a poison cotail.  I like Wine Coolers
but I don't drink that often but I do remember that they sometimes made
my body ache after I drank one ( something that I can't explain the
feeling throughout my whole body ).  I remembered when my nephew came to
stay with me for the summer I let him drink crystal light to and not
coolaid because it had so much sugar.  I remember him telling me that he
had a headache and I just told him to go lay down and I would come and
lay down with him.   I thought it was because it was so hot so I just
made him drink water...(THANK GOD FOR THAT)  he was just 6 years old
then.

The night I saw your website I was drinking Crystal Light.  I threw it
out went and got some water and that's what I've been drinking every
since.  After about 3 days my headaches decreased.  My body didn't ache
so much and my VISION CLEARED.  I wasn't so dizzy after about five days.
Not one more stomach cramp since I stopped.  It has been about 3 weeks
now. I feel much better.  I tell you what Ms Martini I feel better but I
think I have done some long time damage to myself.

My face on the right side still gets a little numb though not like
before.  My ear on the right side gets numb.  My ears still ring but not
like before.  The pain in my neck is still here and behind my ear.  When
I go back to the doctor I'm going to ask for a brain scan and a CT scan
to make sure I don't have a brain tumor because when I look up my
symptoms that's what comes up. I have some of them.  My all over
headache is gone but I do have a headache sometimes on the right side of
my head above my ear and behind my ear in my neck somewhere close to the
base of my scull.  I'm scared but I'm going.  I know if I do that the
ASPARTAME did it.

There so many things that I can remember now and the common denominator
for all is ASPARTAME.  I can remember a female stationed with me at Fort
Hood Texas.  She use to have terrible migraine headaches to the point
where she had to be put on bed rest or quarters for days at a time and I
remember she use to drink Diet Coke and Diet Pepsi.  Some people thought
she was faking but I could see the pain in her face.  If they only
knew.  I'm making a book and I want to take it to the head of the
hospital at Fort Leonard to let him know about this.  I have called the
First Sergeants that I know and told them.  I just retired last April
and the last years in the Army were filled with pain and sickness from
this poison.  The doctor had even given me medicine for Arthritis and
that didn't help either.  Nothing could help because I was still
drinking the poison.  As I get better I realize different symptoms that
I had that are leaving and I know it was the Crystal Light ...Wylers
Lite ( same as crystal light just add something to make it dissolve
better in water) sugar free jello...sugar free gum....

Ms Martini you and the others are helping so many people and I CANNOT
THANK YOU ENOUGH.  To think that I even drank that poison in Saudi and even
then I had to go to the doctor for pain.  When I came back I was
still going to the doctor.  I just cannot believe that the FDA or
congress will allow this to continue.  Don't they care about the
CHILDREN.

I searched and searched for a case about crystal light making someone
sick and I found them.  Well I will email you again after holidays.  I'm
going to the doctor Wednesday to get those test.

THANK YOU AGAIN     WANDA

"Early on I started with a condition under both arms and in the
  groin that I considered to be "Jock itch".  I started using Cortasone 10
  cremes and if I used that at least every other day the condition could be
  controlled and if not the sores were very raw and bloody and boy did it
  burn.  I continued to use the cortosone up until recently.  Also about
  that time I developed a thick scaling in the scalp and around the ears
  that I thought might just be exzema or worse and I used head and
  shoulders shampoo but it didnt control it."

http://groups.yahoo.com/group/aspartameNM/message/1068
classic aspartame case, Fred Keville, 62, diabetic 3 years, quit aspartame
about 3 months ago: Murray 2.10.4

At 02:10 PM 3/9/2004, Fred Keville wrote [to Betty Martini]:

Hello, My name is Fred Keville.  I am a 62 year old caucasion male who
retired as a deputy sheriff in 1997 and who became a metal artist.  Every
thing in my life was going very well health wise until about three years
ago when my personal physician diagnosed me with Diabetes.  From day one
he advised me to use diet foods and drinks such as "diet cokes and others"
as I would have to stay away from the consumption of regular sugar.  I
didnt much like the taste of diet drinks or diet foods but he scared me
enough about my diebetes condition that I switched to only diet foods.  I
began my diabetes life with oral medications of Glucaphage and Avandia.  A
couple of years later I had continued to gain weight and I was falling
apart.  I had occassional headaches that I couldnt explain as I never had
them before.  All of my joints ached constantly especially my knees and
hands.  I thought I had arthuritis and the diabetes was taking hold of my
health in a very negative way.
            Early on I started with a condition under both arms and in the
  groin that I considered to be "Jock itch".  I started using Cortasone 10
  cremes and if I used that at least every other day the condition could be
  controlled and if not the sores were very raw and bloody and boy did it
  burn.  I continued to use the cortosone up until recently.  Also about
  that time I developed a thick scaling in the scalp and around the ears
  that I thought might just be exzema or worse and I used head and
  shoulders shampoo but it didnt control it.  My lower legs and feet were
  swelling and I could no longer wear my favorite cow boy boots and most of
  the time I had to wear soft slippers.
             Traveling became almost impossible.  Besides all of these
  problems I had frequent urination problems and rarely got more than two
  hours of sleep at a time.  I was becoming more and more irratable around
  my wife.  My Doctor during this period of time was totally exasperated
  with me as I couldnt control my blood sugar levels and I continued to
  gain weight and by this time I was up to 320 pounds.
            About a year ago my Doctor put my on insulin in an effort to
  control the blood sugar levels.  He started me out on low doses at first
  but with 3 months I was up to using 65 units of 70/30 humilin in the AM
  and 60 units in the PM.  Sometimes I would test in the morning and I
  would be 105 and sometimes I would be 205.  I was not eating very much at
  all but I could never convince him of that.  By this time I was
  developing so many physical problems that I couldnt keep track of them
  all.  In the morning for the first few minutes my vision was blurry as if
  I had a film coating over my eyes but then it would gradually
  disappear.  I started having ringing or hissing in my ears that woulnt go
  away.  Every morning I would run hot water over my hands so that I could
  close them.  My knuckes were swollen and again I blamed it on
  arthuritis.  I blamed every thing on my age and diabetes.  If I got down
  on my hands and knees to do something I was unable to get back up without
  crawling over to the wall or some furniture.
          One day as I was driving my 84 year old mother to her dialysis
  appointment I began questioning her about any illnesses I might of had
  while growing up.  "I never took you boys to the Doctor while you were
  growing up other than for broken bones."  My brothers and I were very
  active living in the country.  Our diet in those days was meat, potato's,
  fresh vegetables, fruit and home made bread and fresh milk.
         My Mother then said, "you worse off than me" to which I replied
  "He doesnt know what all is wrong with me as all my blood tests are O.K.
  and everything, Im at my wits end.  I was getting real depressed and even
  contimplated ending it all.  My whole life I had been very healthy and
  real strong and now I was as weak as could be.  I then started reading
  books and surfing the internet.  After a few weeks I found
  "Dorway".  Long story short, I cleaned out my pantry and kitchen of all
  the sugar free Jello, pudding, No sugar added IceCream, sugar free
  cookies and Diet Drinks that contained aspertame.  Within 3 days I
  noticed some improvement.  Within 2 weeks I felt like a thirty year old
  again.  I could drop down and do about 5 push ups and wanted to go
  walking around the farm.  My knees completely cleared up and the head
  aches went away.  With the help of using Aloe Vera Gel in my scalp and in
  my shower soap my skin condition cleared up 90 percent.  I have not had
  one bit of under arm and groin rash since I quit using
aspertame products.  Did I mention that I also had been writting a book on
my computer but I was unable to concentrate on spelling even the most
simple of words until I got off that darn poison.  I'm back to writting
again.  I'm now starting up in my metal shop which I stopped doing nine
months ago.
              Now here's the good part.  I went in to see my Doctor about
  six weeks ago about a cyst on my inner thigh that may or may not be
  related to Aspertame use.  Anyway he had already given up on me regarding
  my Diabetes condition and scheduled me to see a Diabetic Specialist for
  the 17th of this month.  I had gain 18 pounds on the last visit with him
  and my blood sugar levels were still out of control.
             He asked me in general conversation, "well how you been
  doing".  I said "Great, never been better"
             By the way Doctor do you still use sugar free food and
  drinks?  Sure, I drink diet pepsi, to which I replied, Well Doc you might
  consider giving them up.  You see Doc, Ive had Aspertame toxins in me
  since you first advised me to use them three years ago.  Besides feeling
  great now, my blood sugar levels have come down to about 95 in the
  morning and about 110 in the PM and besides did you notice what my weight
  is today compared to three weeks ago.  He checked his Nurses notes and
  said your down considerably. about 20 pounds.  I replied, Yeh Doctor and
  I dont even crave any thing sweet any more.  Hmm, very interesting, let
  me know how your improving.  He didnt have a clue about aspertame.  I
  then took the new prescription and went to my trusted Pharmacist who
  didnt have a clue about the effects of Aspertame either.
             Then it hit me, the medical profession doesnt have a clue
  about food additives not even Aspertame.  By the way I also told my
  Doctor that probably a third of his patients probably has Aspertame
  poisoning and he never knew it.  To that he didnt have a response.
             I'm now reading every thing I can get my hands on regarding
  Aspertame.  I've gotten three Diabetic friends off any thing sugar free
  or diet.
             If you dont remember the sixties very well there was a saying
  back then.  "Power to the People".
             If I had my way there wouldnt be a congressman or Senator
  serving one more term unless he got on the band wagon and helped all of
  us victims of this terrrible injustice.  We need to get literature out
  just before election time so any one would know how to vote
  responsibly.  This is the only way we can get enough people
  educated.  "I'M WONDERING, WHAT MORE CAN I DO".  Should I mail all my
sugar free drinks back to where they came from?  No body and I mean
  nobody is so big and powerful that they cant be crippled legally.  Forget
  your scientists and their truth ful results as that hasnt worked and
  never will.  Hit em where it hurts.  You have to ask your self one more
  question.  If the movement to educated people like me is having any
  success then how come this ol' cowboy had to go through three years of
  living hell before I accidently "stumbled" across all the good word that
  you are putting out.
            I'm not going to apologize for the length of this e-mail
  because it all had to be said.  I'm just an average guy who fought for
  his country and did everything asked of me only to be poisoned by my own
  country the good ol' U.S. of A.
           God Bless and Guide you now and always, Your Friend, Fred
  Keville, Lodi, Calif. (209)333-0420 and e-mail /
  <mailto:country@...>country@...

P.S. May I hear back from you, your thoughts./
************************************************************

Appendix J:

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1065
politicians and celebrities hooked on diet sodas (aspartame):
Murray 3.24.4 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 751 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1068 posts in a public searchable archive  120 members

http://groups.yahoo.com/group/aspartame/messages 770 with 16,691 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200 mg/L in drinks adds methanol 98 mg/L
( becomes formaldehyde in body ):  EU Scientific Committee on Foods 7.12.1:
Murray 1.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1055
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 3.11.4

http://groups.yahoo.com/group/aspartameNM/message/1056
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/946
Functional Therapeutics in Neurodegenerative Disease Part 1/2:
Perlmutter 7.15.99: Murray 1.10.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/97
Lancet website aspartame letter 7.29.99:
Excitotoxins 1999 Part 1/3 Blaylock: Murray 1.14.0 rmforall
The Medical Sentinel Journal  1999 Fall; (95 references)
http://www.dorway.com/blayenn.html
aspartame (methanol, formaldehyde) toxicity: Murray 1.1.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1034
Brain cell damage from amino acid isolates (aspartame releases
phenylalanine, aspartate, methanol [formaldehyde, formic acid]  Bowen &
Evangelista May 6 2002: Murray 11.10.3 rmforall

http://www.aspartame.ca/Brain%20Cell%20Damage.pdf
Brain cell damage from amino acid isolates 5.6.2   41 references
detailed 22 page review by James D. Bowen, MD and Arthur M. Evangelista,
former FDA Investigator  orwilly@...

http://groups.yahoo.com/group/aspartameNM/message/628
Rich Murray: Professional House Doctors: Singer:  EPA: CPSC:
formaldehyde toxicity 6.10.1 rmforall

http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity 6.4.1 rmforall   four double-blind studies

http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers:
aspartame toxicity 6.4.1 rmforall    two double-blind studies

http://groups.yahoo.com/group/aspartameNM/message/1018
aspartame toxicity coverup increases danger of corporate meltdown:
Michael C. Carakostas of Coca-Cola: Murray 8.11.3 rmforall
http://www.isrtp.org/new_members/members1.htm
The International Society of Regulatory Toxicology and Pharmacology
Carakostas, Michael C., DVM, PhD Director/Scientific & Regulatory
Affairs   The Coca-Cola Company PO Drawer 1734 Atlanta, GA 30301
T. 404/676-4234   F. 404/676-7166   E-mail: mcarakostas@...
http://www2.coca-cola.com/ourcompany/columns_aspartame.html  [photo]
Aspartame: The world agrees it's safe   By Michael Carakostas, DVM, PhD
Director, Scientific and Regulatory Affairs, Coca-Cola

It is commendable that Carakostas mentions the core problem, albeit
disparagingly:   "During digestion, aspartame yields a very small amount
of methanol-- as do many other food substances. The body converts this
methanol to formaldehyde, which is instantly converted to formate.
Formate is quickly eliminated as carbon dioxide and water."

Plenty of evidence in the mainstream scientific literature since 1973
shows that as much as 30% of the formaldehyde is retained in the body as
toxic, cumulative adducts to the DNA, RNA, and proteins in all cells and
tissues, leading to pointed reports by informed doctors and experts.
Clearly, there are no safe levels for chronic, low-level formaldehyde
exposure.  If just 10% of the methanol from six cans of diet soda is
retained in the body as toxic products of formaldehyde and formic acid,
that is sixty times the EPA limit for allowable formaldehyde from daily
drinking water.

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Formaldehyde was administered for 104 weeks in drinking water supplied
ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
rats beginning at six weeks of age at concentrations of 2,500, 1,500,
500, 250, 50, or 0 mg/L.
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase in total
malignant tumors in the treated groups and showed specific carcinogenic
effects on various organs and tissues.  PMID: 12562630

Surely the authors deliberately emphasized that aspartame is well-known
to be a source of formaldehyde, which is an extremely potent, cumulative
toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested
aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No.      No. of Bioassays  Species    No.       Route of Exposure
108.  "Coca-Cola"     4     Rat       1,999    Ingestion, Transplantal Route
109.  "Pepsi-Cola"    1      Rat          400         Ingestion
110.   Sucrose          1      Rat          400         Ingestion
111.   Caffeine          1      Rat          800         Ingestion
112.   Aspartame      1      Rat       1,800         Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research 7.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/858
RTM: Samuels: Strong: Roberts: Gold:  flaws in double-blind studies re
aspartame and MSG toxicity  8.1.2 rmforall

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 7.10.0 rmforall

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9: rmforall

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/841
RTM: Merisant Co., MSD Capital, Dell Computer Corp., NutraSweet Co.,
JW Childs Assc.: aspartame-neotame toxicity 7.10.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/876
hyperthyroidism (Graves disease) in George and Barbara Bush, 1991--
aspartame toxicity?  Roberts 1997: Murray 10.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/874
re "dry drunk": Bisbort: danger to President Bush from aspartame
toxicity: Murray: 2.24.2  9.29.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 1.5.3 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr   gkokotos@...
"K.H. Schulpis" <inchildh@...>  "G.J. Reclos" <reklos@...>

http://groups.yahoo.com/group/aspartameNM/message/960
aspartame & MSG: possible role in autoimmune hepatitis:
Prandota Jan 2003: Murray 1.15.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/938
aspartame harms mice brain cells: Hetle & Eltervaag: 2001 thesis
abstract: Sonnewald 1995 study, full text: Murray 1.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/346
WebMD: Barclay: Barth:
survey shows aspartame hurts memory in students 11.9.00
http://www.psy.tcu.edu/psy/barth.htm
Timothy M. Barth Department of Psychology    t.barth@...
Texas Christian University TCU Box 298920 Fort Worth, TX 76129
Chairman, Physiological Psychology   817-921-7410

http://groups.yahoo.com/group/aspartameNM/message/760
Kovatsi L, Tsouggas M
The effect of oral aspartame administration on the
balance of magnesium in the rat.
Magnes Res 2001 Sep;14(3): 189-94.
Laboratory of Forensic Medicine & Toxicology, Faculty of Medicine
Aristotle University of Thessaloniki, Greece  kovatsi@...

http://groups.yahoo.com/group/aspartameNM/message/943
aspartame, cell phones, brain cancer July 1999 Hardell:
Murray 1.9.3 rmforall
http://www.medscape.com/MedGenMed/braintumors
Lennart Hardell, M.D., PhD, in 1999 reported in Sweden that both
cell phone use and heavy aspartame use correlate with increased
brain cancers    lennart.hardell@...   +46 19 602 15 46

http://groups.yahoo.com/group/aspartameNM/message/31
Murray: Wurtman: aspartame & seizures 11.9.85 10.30.99
Wurtman RJ   Aspartame: possible effect on seizure susceptibility.
Lancet 1985 Nov 9; 2(8463): 1060.
Richard J. Wurtman, Ph.D.  dick@...  617-253-3091
Professor of Neuroscience
Prof. of Health Sciences and Technology
Massachusetts Institute of Technlogy  Cambridge, Mass. 02139

http://groups.yahoo.com/group/aspartameNM/message/32
Murray:  Drake: aspartame & panic attacks 9.13.86 10.30.99 rmforall
Miles E. Drake, MD
Panic attacks and excessive aspartame ingestion.
Lancet 1986 Sep 13; 2(8507): 631.
Department of Neurology and Psychiatry,
Ohio State University Medical Center,  Columbus, Ohio 43210, USA

http://www.truthinlabeling.org/    Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD   The toxicity/safety of processed
free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999;  6:  259-310.  52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333   adandjack@...

http://www.dorway.com  over 12,000 print pages
Mission-Possible-USA    Betty Martini   770-242-2599
Bettym19@...
http://www.dorway.com/asprlink.html   many links
http://www.dorway.com/nslawsuit.txt    Jeff Martin, Attorney
http://www.dorway.com/doctors.txt
What many informed doctors are saying/have said about aspartame

http://www.HolisticMed.com/aspartame    603-225-2100
Aspartame Toxicity Information Center    Mark D. Gold
mgold@...    12 East Side Drive #2-18 Concord, NH 03301
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

Aspartame Consumer Safety Network and Pilot Hotline  [1987-2001]
Mary Nash Stoddard, Founder & President
P.O. Box 780634  Dallas, TX 75378   .
214-352-4268   marystod@...
http://web2.airmail.net/marystod/index.html
http://web2.airmail.net/marystod/espanol.htm
Toxicology Sourcebook: "Deadly Deception: Story of Aspartame"

Many scientific studies and case histories report:  * headaches
* many body and joint pains (or burning, tingling, tremors, twitching,
spasms, cramps, stiffness, numbness, difficulty swallowing)
*  fever, fatigue, swollen glands  * "mind fog", "feel unreal", poor
memory, confusion, anxiety, irritability, depression, mania, insomnia,
dizziness, slurred speech, sexual problems,  poor vision, hearing
(deafness, tinnitus), or taste  * red face, itching, rashes, hair loss,
burning eyes or throat, dry eyes or mouth, mouth sores, burning tongue
* obesity, bloating, edema, anorexia, poor appetite or excessive hunger
or thirst    * breathing problems, shortness of breath * nausea,
diarrhea or constipation  * coldness  * sweating  * racing heart, low or
high blood pressure, erratic blood sugar levels  * hypothryroidism or
hyperthyroidism  * seizures  * birth defects  * brain cancers
* addiction  * aggrivates diabetes, autism, allergies, lupus, ADHD,
fibromyalgia, chronic fatigue syndrome, multiple chemical sensitivity,
multiple sclerosis, and interstitial cystitis (bladder pain).
************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1066  rmforall@comcast net
Sir John Krebs, Food Standards Agency, criticized for industry bias: Richard
Girling, UK Sunday Times Magazine: Murray 3.28.4 rmforall

http://www.gmwatch.org/p1temp.asp?pid=1&page=1  GM Watch home page

contact GM WATCH here :
address: c/o 26 Pottergate, Norwich, UK, NR2 1DX,
tel: +44 (0)1603 624021 (ask for Jonathan Matthews)     ngin@...

http://www.gmwatch.org/profile1.asp?PrId=43&page=F   Food Standards Agency

GM WATCH daily
http://www.gmwatch.org
---
"The World Health Organization laughs at it. Consumer organisations rail at
it. Environmentalists despair over it. MPs ridicule it. Even the Women's
Institute is unhappy."

Probably the best (and certainly the longest!) article ever written on Sir
John Krebs and the Food Standards agency which he heads
---
Gluttons for punishment
By Richard Girling   The Sunday Times Magazine   March 28, 2004
http://www.timesonline.co.uk/article/0,,2099-1044017,00.html

Its findings smell fishy, its dietary advice is confusing and doesn't amount
to a hill of beans. It's had to eat humble pie and runs around like a
headless chicken. Is Britain's food watchdog dressed mutton as lamb?

The World Health Organization laughs at it. Consumer organisations rail at
it. Environmentalists despair over it. MPs ridicule it. Even the Women's
Institute is unhappy.

In the eyes of many who ought to be its allies, the Food Standards Agency
(FSA) has been worse than a disappointment. To people who care about what
they eat, and who believe that the UK's official food monitor should have a
wider duty than to certify the harmlessness of chemical additives, it has
been the kind of friend that makes enemies unnecessary. It loves GM. Hates
organics. Exalts science to the position once occupied by gods. Pays no more
account to public opinion than it might to the clucking of a hen.

It was not supposed to be like this. When the FSA was set up four years ago,
its aim was "to be trusted as the most reliable source of advice and
information about food". To the pressure groups that had been campaigning
for it, April 2000 looked like the end of an anti-consumer Dark Age. Until
then, food had been the responsibility of the Ministry of Agriculture,
Fisheries and Food (Maff) - the very same outfit that was responsible for
the protection of farmers. Was Maff ever going to uphold the interests of
consumers against the industry? You've only got to look at the degradation
of the farmed landscape to see the answer to that, never mind cast your mind
back to salmonella, foot and mouth, and BSE. Its scientists were forever
telling us that everything was hunky-dory when we all could see that it
wasn't.

The FSA, then, strode into the breach like a toqued crusader. Here was our
champion! It had a meaty annual budget (last year it rose to GBP95m for
England alone), with more than 600 staff at its London headquarters and
another 107 at its outstations in Cardiff, Aberdeen and Belfast.
Agribusiness and food manufacturers had better watch out. Chemically
inflated yields, water-injected meat, fraudulent food labelling, filthy
restaurants and pesticide-riddled greengrocery were yesterday's story.
Tomorrow's was all about the consumer.

The toqued crusader, alas, had feet of pastry. Following a far from
laudatory report by the National Audit Office last year, the agency was
savaged by a plainly exasperated House of Commons public accounts committee
(PAC). Crudely summarised, the PAC's conclusions were that the FSA had
failed to give a public lead on food safety issues; was an incompetent
communicator with a next-to-zero public profile; was unclear about its own
responsibilities, powerless to make local authorities meet their inspection
targets for restaurants and other food outlets, and a political minnow when
set against food-manufacturing giants, the EU and other government
departments with different agendas.

Nothing better illustrates the muddle it has got itself into than the issue
of farmed salmon. It first got snarled up with this in January 2001, when
BBC television screened a controversial documentary suggesting that farmed
fish were being contaminated through the food chain with carcinogenic
dioxins and PCBs. Trouble arose when the presenter, Julian Pettifer, asked
an FSA scientist whether he was happy for children to eat more than a single
portion of farmed salmon a week. Viewers then saw the scientist, Dr Nigel
Harrison, flounder and fail to answer, and an FSA press officer step in to
halt the interview.

The agency compounded this public-relations disaster by complaining to the
Broadcasting Standards Commission. Dr Harrison, it claimed, had been
subjected to an unnecessarily aggressive interview; the programme had
portrayed the FSA as "secretive, heavy-handed and censorial"; it had
unfairly implied that the press officer had ended the interview prematurely,
and that, by filming her intervention, the programme makers had infringed
her privacy. It even complained about criticism of its website. The BSC,
having watched the film, rejected the complaint in its entirety.

Most organisations would have found such humiliation salutary. Lessons would
have been learnt; the website cleaned up; straightforward answers given to
straightforward questions. How, then, did the FSA respond in January this
year when the American peer-reviewed journal Science dropped another toxic
bombshell? Researchers from the University of Albany in New York state had
tested seven tonnes of farmed and wild salmon collected from around the
world. As everyone now knows, the results were devastating. Concentrations
of carcinogenic chemicals in Scottish farmed fish were so high, the
scientists said, that consumers should eat no more than one portion of it
every four months.

As always, the FSA invoked the highest authority: "The World Health
Organization," it said, "set safety levels for dioxins and PCBs in 2001
based exclusively on public health protection. These form the basis of
safety levels set for consumers who eat fish sold in shops."

To check the truth of this, I call the WHO headquarters in Geneva. A
scientist in the chemical-safety department agrees to check the FSA website,
and a few hours later calls back with the verdict. The FSA's assertions, he
says, are not justified by the science it has published. The presentation of
evidence is misleading. The WHO disapproves of the way the FSA has presented
its assessment of risk.

The agency is right about one thing. The WHO does set recommended safe
limits for PCBs, but it does so on the basis of total diet, not on
individual foods. There is no specific recommendation for "fish sold in
shops" (or any commodity, for that matter). Yet the FSA's reassurance had
gone further: "The known benefits of eating oily fish," it said, "outweigh
any possible risks". For it to be a problem you would need to eat more than
our recommendations every week throughout your lifetime."

This makes the man in Geneva laugh out loud. "You can't justify or deny it,"
he says. "They haven't presented data on the website to defend it. We don't
like to see risk assessments presented like this. Consuming above the
recommended level may not cause problems, but it might. There are a lot of
uncertainties involved in picking that level." This is not a new concern for
the WHO. In 2001 it became so worried by what was being said in its name
that it issued a corrective statement: "WHO's recommendation concerns
maximum daily intake of dioxins, not salmon [our italics]."

This time round, the FSA beefed up its response with two scientific papers
of its own, linked from the website in early January. The first of these
uses data collected in 1996, measured against even older WHO recommendations
that have long been superseded. Interesting the paper may be, but it's about
as relevant as last year's weather forecast. WHO scientist's verdict:

"I don't know why it's there." The second paper is about "dioxins and
dioxin-like PCBs in the UK diet". Again it concerns the overall diet, not
specific foods. The survey did include fish, but they were of various kinds,
collected from 24 different places in the UK and "composited into a single
sample for analysis".

Asked how this might help a consumer decide how much salmon is safe to eat,
the WHO expert is unequivocal: "It doesn't." There is nothing wrong with the
science as such <ETH> the problem lies with the way it has been used. "It is
presented very poorly because it's the first thing you're directed to. It
was certainly very confusing to me."

His confusion is widely shared. Sue Davies, the principal policy adviser of
the Consumers' Association, is one of many who return to the question that
won't go away. "The FSA," she says, "should be clearer about whether
consumers should avoid eating more than a single portion of salmon a week."

The problem is that the FSA literally has no answer. It knows that an
"average" balanced diet, containing one portion of oily fish a week, should
do more good than harm. Beyond that, as the WHO expert testifies, it really
has no idea. But the WHO is not the only authority on toxicology. The US
Environmental Protection Agency (EPA) also publishes guidelines for dioxins
and PCBs and, unlike the WHO's, these do relate specifically to fish. It was
for this reason that the Albany group decided to measure their results
against the EPA's guidelines rather than the WHO's.

Dr Paul Johnston, principal scientist in the Greenpeace research laboratory
at the University of Exeter, has no doubt about which ones to trust. "All
WHO says is that you should eat a balanced diet. Assertions that salmon, or
anything else, conforms to WHO guidelines, are untrue. Averages are very
dangerous because they don't take account of individual behaviour. Some
people may eat salmon three times a week, and no advice is given about
that."

He does not believe the FSA under its present leadership is capable of
reform, particularly as so many of its staff were hired from the ranks of
Maff and still carry the echo of that weary old drone's anti-consumerist
dogma. "What's needed," says Johnston, "is root-and-branch reform of the
FSA. Given its various pronouncements on GM and organics, the man at the top
ought to consider his position very, very carefully."

The man at the top is the agency's chairman, Sir John Krebs, a distinguished
zoologist with a specialism in bird behaviour. He is above all a man of
science, whose opinion of GM protesters, organic-food producers and their
customers is like that of a medieval pope for the Muslim hordes. Contempt by
comparison would be an expression of high regard. Criticism of GM food, he
said, was "shrill, often ill-informed and dogma-driven". Organic food was an
"image-led fad".

In appearing to align the FSA with the biotechnology industry, and in
opposing European legislation on the labelling of GM foods, the FSA under
Krebs's leadership bizarrely set itself up in opposition to its own core
supporters. In an otherwise generous appraisal of the agency's work in its
first three years, the Consumers' Association awarded it one mark out of 10
for its performance on GM. In March last year, together with the National
Consumer Council and Sustain, it wrote to Sir John Krebs in terms that left
little room for misunderstanding. The FSA's stance on GM, it said, "while
claiming to be impartial, is anti-consumer and biased in favour of GM
technology".

"Our main criticism is of the FSA's website, entitled 'GM public debate'.
The content is biased, failing to address issues currently facing UK
consumers and selective with the information chosen to be included. In many
cases, what are set out as 'basic facts' give a one-sided view. The FSA's
decision to take a prejudicial view towards GM will affect its credibility
and undo the good work it has done in other areas. The information appears
to have little to do with the desire to have a meaningful debate; rather, it
is a defence of the government's approach".

Nor was this the only stinger in Sir John's postbag. Only a week earlier,
another group of signatories, including the National Federation of Women's
Institutes, the Food Commission, Soil Association, Friends of the Earth,
Greenpeace and the health union, Unison, had blazed away in very similar
terms. "There is a strong consensus amongst consumer and environment
organisations that the published views and statements of the FSA and its
Chair are indistinguishable from those of the pro-GM lobby and do not
properly represent public health and consumer interests." Most bruising of
all for a man of science, the WI group attacked not just the perceived
prejudice of the website but the validity of its research. It deplored the
agency's "willingness to rely on unpublished or confidential corporate data
that is neither independent, nor peer-reviewed nor available to the public".

They might as well have saved their ink. Over a long weekend the very next
month, an FSA "citizens' jury" heard witnesses from interested parties -
environment and consumer groups, scientists, GM companies, food
manufacturers and supermarkets - and delivered its verdict. GM crops, it
said, should not be grown in Britain. The following day, the FSA issued a
press release: "FSA citizens' jury says GM foods should be available to buy
in the UK." This was true: a nine-strong majority of the 15 "jurors" had
decided British shoppers should be able to buy imported GM foods if they
wanted them; but all 15 were unanimous that the crops should not be grown
here. Not only was this not thought worthy of a headline, it was not even
mentioned in the text.

It left Sue Dibb, senior policy officer of the National Consumer Council and
herself a member of the FSA consumer committee, bemused at the FSA's
continuing inability to grasp what was being said to it. "I think it
regrettable that UK government policy did not reflect what consumers were
very clearly saying they wanted. Safety is not the only issue that concerns
many people about GM."

The FSA was out of step not only with British public opinion but also with
the rest of the EU. Alone among European nations, the UK argued against the
European commission's proposal for compulsory labelling of GM
"derivatives" - ie, ingredients such as soya oil, whose provenance is not
detectable in manufactured products. Alone, too, it wanted the entire thrust
of labelling policy reversed - for GM products to count as the norm, and for
the rest to be labelled "GM free". It lost the argument, but only after it
had spent vast amounts of time and energy justifying its position (it
insisted that the law would be unenforceable). It is this that frustrates
people who support the FSA's ultimate aims and objectives, but who find
themselves forced into opposition. "Time spent arguing that extended
labelling can't work," says Sue Dibb, "could have been spent making it
work."

In the end, the agency just looked out of touch. UK food manufacturers and
retailers, being more sensitive to the public mood, are careful to keep GM
ingredients off the shelves; and the labelling of GM derivatives will be a
legal requirement from April 18. The UK government, meanwhile, doggedly
trundles forward in its determination to impose GM crops, come environmental
hell or the high water of public hostility.

If anything exceeds Krebs's enthusiasm for GM, it is his loathing of
organics - another area in which the scientific high ground is claimed by
"conventional" (ie, chemically dependent) agriculture. Krebs is very fond of
the scientific high ground, and scathing of the media bias he descries on
the lower slopes. In the autumn of 2000, he was one of a number of
scientists invited by the Royal Institution and the Social Issues Research
Centre (SIRC) to draw up new guidelines for journalists reporting on science
and health. "As chair of the Food Standards Agency," he said at the time, "I
feel that people in our society should have access to accurate and balanced
information about food safety and nutrition in order to make sensible
decisions about what they eat. I very much hope that with these guidelines
we will reduce the distortions and sensationalism which so often are
associated with stories about what we should or should not eat."

The guidelines themselves were largely unexceptionable, though the irony of
that "balanced information" was not lost on aficionados of the FSA website.
The odd eyebrow was raised, too, at the involvement of the SIRC, whose
website appears even more violently anti-organic than the FSA's own.

"It was inevitable," it says, "that when Sir John Krebs first punctured the
myths surrounding organic food, he would become a target for both personal
abuse and zealous attempts to prove him wrong." Oddly, this is the first
sentence of a piece which itself is larded with personal abuse, and which
zealously attempts to prove wrong the author of a Soil Association report on
the nutritional value of organics. "No journalist," it complains, "seems to
have explored the credentials of [the author] Shane Heaton. If they had
bothered to do so they might have been more concerned about his so-called
'results'." And the damning evidence from Heaton's background? That he
trained with the Institute for Optimum Nutrition, whose "founding patron was
Linus Pauling - the man responsible for the now discredited idea that
massive doses of vitamin C are effective in preventing colds and other
ailments, and even cancer".

What it neglects to add is that Pauling was a double Nobel laureate
(Chemistry, 1954; Peace, 1962) and an unlikely vehicle for a "guilt by
association" smear. This leaves the SIRC and, by association, Sir John
Krebs, ducking the ricochets. Is this the standard of scientific objectivity
it wants to impress upon the media? If even a Nobel laureate can be wrong,
then how can scientists continue so arrogantly to proclaim their own
infallibility? And if people are to be judged by the company they keep, what
about the SIRC's own food-industry funding, and its association with a
commercial market-research company? What about the FSA's warm embrace of
officials who thought it good practice for animal protein to be fed to
cattle? If this is scientific objectivity, then you might as well hand
editorial control of Nature to the editor of the Daily Mail.

Half-truths abound. Krebs says people who buy organic food are "not getting
value for money". Well, they are and they aren't. Unlike customers for
"conventional" foods, they are indeed paying the real price for what they
eat, without much in the way of subsidy. The true cost of supermarket food
can be seen in the degradation of the farmed landscape, from which every
kind of agricultural pollutant floods into groundwater and streams, with
devastating effects on wildlife. The Department for Environment, Food and
Rural Affairs (Defra) calculates that the total annual cost to the water
industry of scrubbing agricultural pollutants from the public supply is
£225m. Find this on the FSA website if you can. You will look in vain, too,
for any acknowledgment that the health of inland waterways is as much an
issue for consumers as the price of carrots. Krebs himself insists that, far
from having a coherent argument on its side, the organic industry "relies on
image", and that there is no advantage to be had from eating food free from
pesticide residues. Indeed, he told the Guild of Food Writers in October
2001 that pesticides had passed the scrutiny of an expert committee and were
therefore preferable to the many natural toxins in fruit and vegetables that
did not have the benefit of official approval.

The irony here is that Defra itself has published an action plan encouraging
organic food. In an enthusiastic foreword, the secretary of state, Margaret
Beckett, commends organics for offering "real benefits for the environment".
Peter Melchett, policy director of the Soil Association and a former Labour
environment minister, is both encouraged and dismayed. "There is a huge
shift in government thinking on sustainable food policy," he says. "New
science is coming out all the time to show environmental, food quality and
health benefits - and it's in the latter area that the FSA is still
resistant.

"It's a real pain for us because it affects what the organic sector can say
to its customers. For example, organic food contains less of the
hormone-disrupting chemicals that may be implicated in the reduction of
men's sperm counts. This is serious science, but the Advertising Standards
Authority, which follows the FSA's lead, won't allow us to mention it.
Neither can we mention that pesticides are particularly dangerous for the
very old and the very young, and especially to the unborn foetus. The reason
given is that it would cause undue alarm, but scientifically it's not
controversial." It's the same with meat. "Beef from cattle fed on grass has
lower levels of saturated fat and higher levels of unsaturated fat, which is
healthier. Again this is not controversial as science, but you'll be in
trouble with the ASA if you want to say that organic meat is better for
you."

There have been other examples of what he calls "crass behaviour" by the
FSA. One of these was its attempt to design simple tests to check the
authenticity of claims on food labels. "Because they didn't understand that
organics was a process - involving the way you look after your soil and the
way you treat your animals, all laid down in a very precise and demanding
set of standards - they treated it as if it were just another claim on a
label, like 'free range' or 'no added sugar'. In any other market sector
they would have talked to the industry, but they never said a word to us
about what they were doing. They spent hundreds of thousands of pounds
trying to devise tests to show whether artificial nitrogen had been applied
to crops or not; but it's useless. It means that if you were a conventional
farmer and didn't apply nitrogen, you could sell your crop as organic."

Even so, he still doesn't see this as anti-organic mendacity. "It's not a
conspiracy. It's a cockup." The same explanation might fit some of the other
shortcomings catalogued by the public accounts committee. Its principal
complaint - that after four years the agency "has not yet demonstrated
convincingly that it is able to lead on issues of food safety and standards,
and is an authoritative and trusted voice where there is public doubt" - is
devastating. Astonishingly, only 3% of the public said they would turn to it
for advice. There remains confusion, too, about division of responsibilities
between the FSA and other arms of government (Defra on meat imports, for
example, and the Department of Health on nutrition).

Successes? There have been a few. The agency recently saved us from
donkey-meat salami. It fingered wholesalers and retailers who mis-sold
"varietal" potatoes (35% of King Edwards in its survey were wrongly
labelled). And it honoured a promise, given by its chief executive, Jon
Bell, to the public accounts committee, that it would do more to "name and
shame" the guilty. It has tested sausages for salt, fat and nutritional
content; and tested bread and a range of ready meals for salt, which it is
keen for us all to eat less of. Pizzas, canned spaghetti, baked beans and
soups are next. It is also taking a close interest in Coca-Cola's use of the
word "pure" in its marketing of the processed Sidcup tap water, Dasani.

Meanwhile the giants of the food industry still get away with the kind of
labelling that allows products with a 16% fat content to be sold as "Lite",
and those with 10% fat as "90% fat free". Local authorities continue to fail
in their statutory duty to inspect restaurants, butchers' shops and other
food outlets, and the public stomach continues to heave. In 2001, 5.5m
people said they'd suffered food poisoning in the previous year, and 4.2m of
these blamed restaurants or other caterers. The FSA does have power to move
in on negligent local authorities but - although many are failing
abysmally - it has yet to do so. Instead, it is relying on education. If it
is to realise its ambition of a 20% reduction in food poisoning within four
years, the learning curve will need to be steep. The PAC heard that half of
all catering staff do not wash their hands before preparing food, and that a
third don't wash after using the lavatory.

Response to criticism is not the FSA's strong point. As ever, salmon is the
classic example.

Question: "Could you answer the criticism that you wrongly imply that the
WHO has set specific safe limits for dioxins and PCBs in 'fish sold in
shops'?"

Answer: "We did not say that WHO had set safe limits."

Truth: Remember the website? "The levels of dioxins found in farmed salmon
are below the safety levels set by the World Health Organization. The WHO
set safety levels for dioxins and PCBs in 2001 based exclusively on public
health protection. These form the basis of safety levels set for consumers
who eat fish sold in shops."

It may be possible, by close textual analysis, to reconcile these apparently
conflicting statements, but there is no doubting the inference that most
ordinary readers may be expected to draw: the WHO does set specific limits
for farmed fish, and Scottish salmon falls within the margin of safety. As
we now know, this is simply not true. At every turn, the route to clarity is
blocked by theoretical concepts of "average" or "balanced" diets. Already
three years have passed since doubts about the safety of salmon first
emerged in public - three years that the FSA has spent in issuing denials
and reassurances. Only now, three years since it pulled the plug on the BBC,
has the agency appointed a panel of experts to advise on the "risks and
benefits" of eating more than one portion of salmon a week. You'll get the
answers in the autumn.

On other issues it is no less evasive. Asked to justify its attack on the
scientific competence of the EPA, it merely reiterates its faith in the WHO,
and other official bodies in the UK and US, whose findings it prefers. There
is no engagement with the issue. On questions of organics it remains simply
bewildering. "The agency has always made it clear," it declares, "that it
would not be appropriate for it to make statements supporting any particular
food production scheme." Yet at the same time it has "consulted on a
proposal" to compare the nutrient content and pesticide residues in organic
and conventionally grown fruit and vegetables. By implication, if such a
study goes ahead and demonstrates a clear advantage of one side over the
other, then it must debar itself from making any recommendation based upon
the result.

This February it found itself in deep trouble with another group of MPs, the
House of Commons select committee on environment, food and rural affairs.
This time the whipping was for its costly mishandling of the shellfish
industry, after flawed toxin monitoring had caused prolonged closure of
cockle beds in England and Wales. The FSA, it said, "had not lived up to its
core value of being open and accessible". Its standards of communication and
co-operation had been so poor that they had led to "an atmosphere of
distrust and, at times, hostility".

The science had been a shambles, and the FSA had been slow to accept the
possibility that its methodology could be at fault. "It is both astonishing
and unacceptable," said the committee, "that the three laboratories
conducting statutory toxin monitoring used different methods, and more
importantly, did not appear to have a common standard for determining
whether a result was positive or negative."

But there is no sign that anything is about to change. An FSA spokesman
immediately popped up in a BBC studio to declare that the agency had done
nothing wrong. His excuse, which cannot have been better designed to cause
mirth in anybody who had followed the salmon saga, was this: for the sake of
public safety, it had been essential to adopt a "precautionary approach in
the face of scientific uncertainty".

One portion a week, anyone?
******************************************************************


Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1065
politicians and celebrities hooked on diet sodas (aspartame): Murray 3.24.4
rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 751 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1068 posts in a public searchable archive  120 members

http://groups.yahoo.com/group/aspartame/messages 772 with 16,688 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
( becomes formaldehyde in body ):  EU Scientific Committee on Foods 7.12.1:
Murray 1.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1055
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 3.11.4

http://groups.yahoo.com/group/aspartameNM/message/1056
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall
************************************

http://groups.yahoo.com/group/aspartameNM/message/1065
politicians and celebrities hooked on diet sodas (aspartame): Murray 3.24.4
rmforall

http://www.usatoday.com/news/politicselections/nation/president/2004-02-03-candi\
dates-eat_x.htm

Candidates adopt unhealthy diet for road      Feb 3 2004

WASHINGTON (AP) - A typical day of eating for Democratic presidential
candidate John Edwards while on the campaign: Breakfast, a McDonald's
"Deluxe Big Breakfast" platter with two hot cakes, scrambled eggs, sausage
and a biscuit. Lunch, a McDonald's cheeseburger. Later, a McDonald's chicken
sandwich and some cookies. And lots of Diet Cokes - about 10 cans -
throughout the day.

[Photo of John Edwards swigging a Diet Coke]  On tight campaign schedules,
Sen. John Edwards drinks lots of Diet Coke throughout the day.
By Lloyd Jones, AP

Edwards, 50, is not alone among the candidates whose eating habits don't
reflect a five-star palate during the campaign.

Food on the fly and exercise on the run sums up the candidates' diet and
fitness regimens. In a hot race to fill the ultimate prized political seat,
the fuel these candidates are getting is mostly junk: fast food, sweets,
sodas. And exercise? Well, there's not nearly enough of it, some of the
candidates say.

Wesley Clark, 59, eats a lot of "garbage," his son Wes Jr. says. His
weaknesses: Cheetos and Gummi Bears.

And Howard Dean, who by December had gained 12 pounds during his time on the
campaign, snacks constantly. His choices aren't necessarily healthy ones. He
favors chocolate chip cookies and doughnuts, and he often eats chocolate
peanut M&Ms on the plane.   "I think his diet could be better," said his
wife, Judy, who sent him some clementines at one point.

Tall and lean John Kerry, on the other hand, is not getting much food at all
these days, or exercise, and complains loudly about the latter. An active
man who likes to play exhibition hockey games and go kite-surfing, he
recently groused he's "in the worst shape of my life" because of the lack of
physical activity.

[Photo]  By Kevin Lamarque, AP
Sen. John Kerry literally grabs lunch on the fly eating a piece of cake on a
helicopter escorting him through N.H.

Kerry, 60, skips meals because of his harried campaign schedule. His staff
spots him with the occasional milkshake. He attends few events where food is
actually served, so it falls largely on staffers to find ways to get him
meals.

He said his last real exercise was a bike trip he took last summer for a
charity fund-raiser, and there is no time during the day to work out.   He
said that after the primary season, he'll tell staffers to set aside some
time each day for exercise.

The Clark campaign goes out of its way to scout swimming pools for the
retired Army general, a former swim team captain. He swims mostly at YMCAs
for about 40 minutes.   Clark doesn't drink much caffeine. "He is sick of
the quick meals and junk food of the trail," said spokesman Matt Bennett.
"He does his best to eat right."
For all his fast-food gorge-fests, Edwards runs religiously - five miles a
day. He does an eight- to 10-minute mile, depending on whether he's outdoors
or on a treadmill, which is faster.     This helps counteract the fatty
foods.

"It's not pretty," said the North Carolina Democrat's campaign spokeswoman,
Jennifer Palmieri, describing his meals on a recent day in South Carolina.
While in Iowa, Edwards was particularly fond of "butter burgers," she said.
Those would be burgers cooked with a pat of butter on them.   But when he's
in an expensive restaurant, he'll order fish or steak. "He doesn't eat a lot
of vegetables" she said.
Still, Edwards is in good health, with cholesterol in the normal range
despite his fatty diet, she said, adding, "We share desserts."

As a devout Orthodox Jew, Joe Lieberman, 61, stays kosher according to a
stringent set of dietary restrictions based on commandments in the Bible.

Dean, 55, who doesn't drink caffeine and gave up alcohol several years ago,
says he likes to spend time doing something recreational outdoors when he
can.
"He eats on the run, sleeps on the plane," said Jay Carson, Dean's
spokesman. "His schedule is so packed everyday that he rarely gets to do any
exercise. He laments that because he is a fan of the outdoors."   Dean and
his wife are both medical doctors and know about healthy habits. But it's
proving hard in the campaign for him to practice what doctors preach.
"When I was on the bus in Iowa, all I saw were candy bars and chips," his
wife said in a New Hampshire TV interview. "I don't know if the good food
was hidden, or it just wasn't there."

Dennis Kucinich, 57, a vegan, stays equipped with oatmeal, pita and hummus.

Al Sharpton, 49, who is fond of Southern cooking - fried chicken and potato
salad - tries to exercise in the morning on the treadmill at the hotel where
he's staying. He awakens between 5 a.m. and 6 a.m. to make sure he gets the
job done.   He eats one main meal a day, preferably before 9 p.m., with
snacks spread out through the day. He disavows sweets. But caffeine is a
must, campaign spokeswoman Rachel Noerdlinger said.

Copyright 2004 The Associated Press. All rights reserved. This material may
not be published, broadcast, rewritten or redistributed.
© Copyright 2004 USA TODAY, a division of Gannett Co. Inc.
**************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1027
Senator John Edwards, avoid Diet Coke (aspartame toxicity): Murray 9.28.3
rmforall

http://groups.yahoo.com/group/aspartameNM/message/1037
Joe Trippi, heavy user of Diet Pepsi (aspartame toxicity), Dean's campaign
manager: Murray 11.16.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/874
re "dry drunk": Bisbort: danger to President Bush from aspartame
toxicity: Murray: 2.24.2  9.29.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/876
hyperthyroidism (Graves disease) in George and Barbara Bush, 1991--
aspartame toxicity?  Roberts 1997: Murray 10.9.2 rmforall
***************************************************************

diet coke (aspartame toxicity) use by candidates: Murray 1.30.4

Dean sips Diet Coke: Bush, Gore, Clinton, Edwards, Clark, Dean, Trippi:
diet soda (aspartame) toxicity issue: Lyons: Murray 1.16.4

http://www.rutlandherald.com/hdean/74353
Dean regales Democrats at fund-raiser in Barre
November 9, 2003     By CLAUDE R. MARX Vermont Press Bureau
claude.marx@...; claude.marx@...
BARRE - Less than a year before election day and about two months before the
first delegates are picked, former Gov. Howard Dean brought his presidential
campaign here Saturday to reminisce about his early political career and ask
for help in getting a new job....
Even as he sipped a Diet Coke while waiting to be introduced by state
Chairman Scudder Parker, he signed name tags and campaign literature....

From: "Rich Murray" <rmforall@...>
To: <vlyons@...>
Cc: <wlyons@...>; <kconnell@...>;
<occasoc@...>
Subject: Dean, Trippi, diet soda toxicity issue
Date: Sunday, January 11, 2004 10:51 PM

http://www.sevendaysvt.com/-thisweek/col/track.html   01.07.04

Peter Freyne  insidetrackvt@...

Also on the food and beverage front, Sen. Ginny Lyons has introduced S.241.
It proposes to "help prevent childhood obesity by directing the state board
of education to adopt nutrition standards for public schools; and by
defining physical education as a daily program of moderate to vigorous
physical activity."
The bite in Skinny Ginny's bill comes in the last sentence:
"Only food and beverages which meet the nutritional standards
adopted by the state board may be sold on school grounds
between one half hour before the start of the school day and
one half hour after the end of the school day."
Can you say bye-bye, Coca-Cola?
***************************************************************************

Bush, Gore, Clinton,  Edwards, Clark, Dean, Trippi:
diet soda (aspartame) toxicity issue: Lyons: Murray 1.13.4

Jan 11 2004   Hello Senator Virginia "Ginny" Lyons,

About a dozen activists on the world Net
competently alert people about aspartame toxicity.

Famous users include Bush, Clinton, Gore, John Edwards,
Clark, Dean, and Dean's campaign manager, Joe Trippi
(widely noted as a very heavy user of Diet Pepsi).

Can you help me find contact people who can in turn alert
these key players to the personal and public hazards?

Surely, this deserves to be put in the limelight as a political issue.

Thanks,  Rich Murray
***************************************************************

[ http://www.mcall.com/     letters@...  news@...
101 North 6th St.  Allentown, PA 18101  (610) 820-6500
frank.devlin@...    610-778-2235  ]

http://www.mcall.com/features/all-hhtjan09.story
From The Morning Call
Mainlining Diet Coke    By Frank Devlin    of  The Morning Call  January 9,
2004

Believe it or not - drinking Diet Coke makes dreams come true.

Don't believe it?

Then how do you explain the way Diet Coke keeps popping up as the celebrity
soda of choice? Surely there's some link between success and this
caffeinated, chemically sweetened serum.

Take Harvey Weinstein, head of the Miramax Pictures movie studio. U.S. News
and World Report reports Weinstein has a limousine ''outfitted with video
screens and seat pockets stocked with Diet Coke.''

Or presidential candidate John Edwards, who would ''chain-drink Diet Cokes''
when he was a hotshot personal injury lawyer, according to the Charlotte
Observer, and who's drinking about 10 cans a day now on the campaign trail.

Bill Clinton, Donald Trump and Major League Baseball Commissioner Bud Selig
are also reported to be devoted Diet Coke drinkers.

Why, Mankind himself drinks Diet Coke - that's Mankind the retired
professional wrestler, not all of humanity, of course.

And it did wonders for him.

Once upon a time, Mankind, aka Mick Foley, was just your average 310-pound
brute missing front teeth and pining for a post-wrestling career.

Naturally, he decided to try his hand at writing serious fiction.

So, according to Entertainment Weekly, he pumped himself full of Diet Coke
and, voila, cranked out a fine novel.

If Foley's ''Tietam Brown'' still doesn't convince you of Diet Coke's
powers, then consider Bill James.

James was a baseball fan who wrote books of statistical analysis that,
despite their brilliance, for some reason failed to influence the way Major
League Baseball teams made personnel decisions.

But now, more and more baseball bigwigs heed his theories. The Boston Red
Sox even hired him as an adviser.

James drinks Diet Coke, too.

Lots of it.

In a recent New Yorker profile, he was quoted as saying - tellingly, if not
profoundly - ''Would you get us a Diet Coke from the refrigerator over
there?''

But if you really want insight into the Diet Coke equation, consider
Columbia University physicist Janet Conrad, a leader in the field of
neutrino studies. .

This scientist, when not teaching at an Ivy League school, conducts
experiments at the Fermi National Accelerator Laboratory in Illinois that
could change our very understanding of the universe's building blocks.

She says further study of neutrinos - subatomic particles that require
tremendous effort to track - could even ''open the door to the idea of extra
dimensions.''

Her Diet Coke connection?

''It's certainly made me a more effective person,'' says Conrad, who starts
each day with two 12-ounce cans of the caffeinated drink (45 milligrams per
can, about one-fourth the caffeine, per ounce, in coffee) and goes on to
drink about six more cans before she turns in.

That's on a day that's not particularly challenging, she says.

On challenging days she drinks much, much more.

''Part of what helps me keep my momentum going is the Diet Coke. I mean that
quite seriously,'' she says.

''I need to be very sharp to help me get things done. When I give a talk and
I am excited about something, the audience gets excited. If I'm sort of
flat, then the audience will be flat.''

Conrad, 39, says her diet-soda habit dates to high school, when she was
stuck on saccharine-sweetened Tab.

Why Tab? ''It was probably what was in the machine at the hardware store
where I worked'' in Wooster, Ohio, she says.

Conrad says she lamented the replacement of saccharine - thought to cause
cancer - with aspartame, marketed as Nutrasweet and Equal, in the 1980s.
Without the saccharine, she didn't like Tab's taste anymore.

In college, she and a friend searched for aspartame soda they could stomach.

They eventually decided on Diet Coke.

Conrad was such a devotee of saccharine-sweetened Tab that she honors its
memory by rotating possession of a single, unopened bottle with the same
college friend.

''We actually have this bottle of Tab, which is the last bottle of
non-Nutrasweet Tab in the world. We give it back and forth to each other.
She gave it to me for my wedding. She has it now. I think I gave her the
bottle when she bought her house.''

Nevertheless, Conrad grew to love Diet Coke. ''I'm very much addicted,'' she
says.

Conrad prefers it from a can. ''What's really sad is I prefer it warm,'' she
says. ''It sort of evolved out of laziness, out of not bothering to put it
in the refrigerator.''

Dave DeCecco, spokesman for Pepsi-Cola North America, says his company
doesn't keep track of which soft drinks celebrities and other notables are
reportedly drinking.

''It's nice'' if someone publicly consumes your product for free, the way
Edwards, et al., are doing for Diet Coke, DeCecco says. But when it comes to
the diet soda war, he says, sales are what matters, and Diet Pepsi's have
been growing faster than Diet Coke's since 2000.

Diet Coke is still a bigger seller, though, with about 71/2 percent of the
soft-drink market, compared to 51/2 percent for Diet Pepsi, according to
Beverage Digest magazine.

Sounding unconcerned with the notion that Diet Coke has a higher media
profile than his brand, DeCecco even questions the premise, which, he says,
seems to be a ''a pretty unscientific survey.''

But it's all there on the computer screen when you search the LexisNexis
media database (nexis.com).

A recent Nexis power search for news pieces containing the words Diet Coke
over a recent 60-day period produced 527 hits, including:

An interview with Jimmy Carter, who was talking about his new book and
''sipping on a Diet Coke'' (Newsday, Dec. 1).

An article about a North Carolina death row inmate whose last meal included,
curiously, a non-fattening Diet Coke (Associated Press, Nov. 7).

A basketball column pointing out that Houston Rockets coach Jeff Van Gundy
''drinks Diet Coke as if it's water'' (The Seattle Times, Oct. 9).

The same search parameters for Diet Pepsi produced only 137 hits, including
one article that includes a celebrity dis of Diet Pepsi.

An Oct. 30, 2003, Phoenix New Times profile of ''Legally Blonde'' author
Amanda Brown has Brown's assistant seeking a Diet Coke for Brown before a TV
interview. But only Diet Pepsi is available. Brown's assistant says no
thanks, Brown will settle for water.

Conrad says Diet Pepsi is too sweet.

Diet Coke drinker Ericka Kirkpatrick of Coopersburg, spotted in Bethlehem
recently holding a 20-ounce bottle, says it's hard to explain why she
doesn't like Diet Pepsi's taste. ''It's got a bite,'' she says.

All she knows is ''if I send someone out to get me a Diet Coke and they come
back with a Diet Pepsi I will not drink it. I'll go back out myself and get
a Diet Coke.''

''I'm very picky,'' the 29-year-old real estate agent says.

Diet Coke fan and pop culture pundit Michael Musto of the Village Voice
refrained from dissing Diet Pepsi.

However, he says in an e-mail, he can ''personally vouch for and in fact
have mentioned it a few times myself'' in Village Voice columns.

''It just seems to be the sensible thing to drink'' at the entertainment
industry parties he covers, he says. ''It's tasty, gives you a rush, and
keeps the pounds off. No, it's not exactly a healthy treat, but at least
it's not booze.''

Musto says he doesn't know why Diet Coke seems to hold sway with
celebrities.

But Coca-Cola spokesman Mart Martin says Diet Coke's cache is something
Coca-Cola, which introduced the drink in 1982 with a gala party at Radio
City Music hall, has been aware of for years.

''It has achieved sort of an icon status,'' he says.

''You see Diet Coke popping up a lot in photo spreads in magazines'' that
feature celebrities, he says. ''Those are not product placements'' paid for
by Coca-Cola, he says. ''That is, in fact, what they are drinking.''

''There's a certain stylishness'' to Diet Coke, Martin claims, crediting the
''clean look'' of the silver can.

Conrad says she drinks soda instead of coffee because, with less caffeine,
''it gives you a lower and steadier dose of the thing that keeps you
going.''

Kirkpatrick says she switched from caffe mochas to Diet Coke after
graduating from Penn State - where ''they had a great cafe that made the
best mochas'' - and returning home to the Lehigh Valley.

''Around here,'' she laments, ''they don't make great mochas.''

She drinks four or five 20-ounce bottles of Diet Coke a day.

Anita Hirsch, nutritionist at the Lehigh Valley Racquet and Fitness Centers,
says the caffeine from four 20-ounce Diet Coke bottles -300 milligrams -
shouldn't cause health problems for healthy people who aren't pregnant.

Tina Amato, a registered dietitian at the Allentown Health Bureau, agrees.
But both say there are concerns other than caffeine content about drinking
massive cola quantities. Hirsch says research indicates aspartame, used
throughout the diet soft drink industry, ''could be a migraine trigger'' in
some people.

Amato says diet soda may be replacing healthy beverage choices such as
low-fat milk and water. And the phosphoric acid in diet soda ''causes
calcium depletion,'' Amato says. ''We all need more calcium.''

Diet soda ''has no nutritional value whatsoever,'' she notes, advising that
people drink no more than two a day.

Kirkpatrick says she's aware of the calcium problem and isn't happy about
drinking so much Diet Coke.

But she stopped making New Year's resolutions to kick it a couple of years
ago, she says. ''Some people have a gambling problem,'' she says. ''I have a
Diet Coke problem.'' She gets cranky if she stops drinking Diet Coke, she
says.

She figures she'll finally give it up if she gets pregnant some day. Conrad
says she doesn't worry much about Diet Coke's possible health risks.

She does believe that ''feeding yourself one thing for long periods of time
isn't good. The human body is made for a varied diet.''

But she makes an exception for Diet Coke.

frank.devlin@...    610-778-2235   Copyright © 2004, The Morning Call
**************************************************************

From: "Richard T. Murray" <rmforall@...>
To: <joanchad@...>
Subject: danger to President Clinton from ideosyncratic toxic reaction to
aspartame in diet sodas 5.12.99
Date: Sunday, May 16, 1999 9:27 AM

May 12, 1999
From: Richard "Rich" T. Murray, M.A.   465-70-0817   July 3, 1942
Room For All     rmforall@...
1943  Otowi Drive
Santa Fe, NM 87505
505-986-9103  505-920-6130 cellular VoiceStream
http://www.healthandmoneytips.com/ezine/v1i3/page5.html
12-page summary: Aspartame: Methanol Toxicity

To: Cptn. Eleanor C. "Connie" Marino, USN
Physician to the President
White House Medical Unit #105
Whashington., D.C. 20502
202-757-2481  2483 fax

Dear Cptn. Marino:

This post presents evidence that indicates that President Clinton
could be in danger right now from a not unusual idiosyncratic toxicity
reaction to a common food additive, aspartame (NutraSweet, Equal),
about 200 mg in every can of diet soda.  To simplify, 10% of aspartame
is methanol (wood alcohol), a component of the molecule, which is
immediately released into the body after ingestion.  This dose of
methanol is thus 20 mg from each can, while the EPA limit for drinking
water is 7.8 mg daily.  Methanol is a deadly cumulative poison. So
aspartame provides methanol, which converts to formaldehyde in the
tissues, as proved in a 1998 radioactive tracer study in Spain:

Life Sci 1998;63(5):337-49     From PubMed

Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas,
Sr. Jordi Virgili, X. Remesar,  Dr. Jose Antonio Fernandez-Lopez,
Dr. Marià Alemany Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
alemany@...     bioq@...

Formaldehyde derived from dietary aspartame binds to tissue components
in vivo.  Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M, Departament de Bioquimica i Biologia
Molecular, Facultat de Biologia, Universitat de Barcelona, Spain.

"It is concluded that aspartame consumption may constitute a hazard
because of its contribution to the formation of formaldehyde adducts."

Woodrow C. Monte, Ph.D., Professsor of Food Science, Director of the
Food Science and Nutrition Laboratory, Arizona State University, Tempe,
Arizona  85287
6411 South River Drive  #61
Tempe, Arizona   85283-3337
United States of America
Phone/Fax 001 602-965-6938
woody.monte@...

Dr. Woodrow C. Monte, "Aspartame: Methanol, and the Public Health,"
Journal of Applied Nutrition, Volume 36, No. 1,  pages 42-54, 1984.
This study is available at:  http://www.dorway.com/wmonte.txt   .

Abstract:   Aspartame (L-aspartyl-L-phenylalanine methyl ester), a new
sweetener marketed under the trade name NutraSweet, releases into
the human bloodstream one molecule of methanol for each molecule of
aspartame consumed.

This new methanol source is being added to foods that have
considerably reduced caloric content and, thus, may be consumed in
large amounts.  Generally, none of these foods could be
considered dietary methanol sources prior to addition of aspartame.
When diet sodas and soft drinks, sweetened with aspartame, are used
to replace fluid loss during exercise and physical exertion in hot
climates, the intake of methanol can exceed 250 mg/day or 32
times the Environmental Protection Agency's recommended
limit of consumption for this cumulative toxin (8).
[EPA limit: 7.8 mg/day in water.  A 12-oz can of diet soda gives
20 mg methanol.]

There is extreme variation in the human response to acute
methanol poisoning, the lowest recorded lethal oral dose
being 100 mg/kg [10,000 mg for a 100 kg person] with
one individual surviving a dose over ninety times this level (55).
Humans, due perhaps to the loss of two enzymes during evolution, are
more sensitive to methanol than any laboratory animal;  even the monkey
is not generally accepted as a suitable animal model (42).  There are
no human or mammalian studies to evaluate the possible mutagenic,
teratogenic, or carcinogenic effects of chronic administration of
methyl alcohol (55).

The average intake of methanol from natural sources varies but
limited data suggests an average intake of considerably less than 10
mg/day (8). [A 12-oz can of diet soda has 20 mg methanol.]  Alcoholics
may average much more, with a potential range of between
0 and 600 mg/day, depending on the source and in some
cases the quality of their beverages (15).

Ethanol, the classic antidote for methanol toxicity, is found in
natural food sources of methanol at concentrations 5 to 500,000 times
that of the toxin (Table 1).  Ethanol inhibits metabolism of methanol
and allows the body time for clearance of the toxin through the lungs
and kidneys (40, 46).

The question asked is whether uncontrolled consumption of this
new sweetener might increase the methanol intake of certain
individuals to a point beyond which our limited knowledge of acute
and chronic human methanol toxicity can be extrapolated to predict
safety.  [end of Abstract]

"Many of the signs and symptoms of intoxication due to methanol
ingestion are not specific to methyl alcohol.  For example, headaches,
ear buzzing, dizziness, nausea and unsteady gait (inebriation),
gastrointestinal disturbances, weakness, vertigo, chills, memory
lapses, numbness and shooting pains in the lower extremities hands and
forearms, behavioral disturbances, and neuritis (55)."

Stephen K. Van Den Eeden, T.D. Koepsell, W.T. Longstreth, Jr,
G. van Belle, J.R. Daling, B. McKnight, "Aspartame ingestion and
headaches: a randomized crossover trial," 1994, Neurology, 44, 1787-93:
Division of Research, Kaiser Permanente Medical Care Program
3505 Broadway, Oakland, CA 94611-5714      skv@...
510-526-6020   510-596-6100

In their introduction, they commented:

"In addition, the FDA had received over 5,000 complaints as of July,
1991 in a passive surveillance system to monitor adverse side effects.
(17)  Neurologic problems constitute the primary complaints in these
and several other case series, with headaches accounting for
18 to 45 %,depending on the case series reported. (17-19)"

A fairly complete list of the usual symptoms in the many cases includes:

headaches, all kinds of body and joint pain (or burning, tingling,
tremors, twitching, spasms, or numbness)

"mind fog", "feel unreal", poor memory, confusion, anxiety,
irritability, depression, mania, insomnia, dizziness, slurred speech,
ringing in ears, sexual problems, nausea, seizures, poor vision,
hearing, or taste

fatigue, weakness

red face, itching, rashes, burning eyes or throat

hair loss

obesity, bloating, poor or excessive hunger or thirst

diarrhea or constipation

breathing problems, asthma

racing heart, high blood pressure, erratic blood sugar levels.

Obviously, the neurotoxicological impairments are critical concerns
in the case of a war-time President.

Ralph G. Walton, M.D., Ph.D.,
Prof. of Clinical Psychology, Northeastern Ohio Universities,
College of Medicine, Dept. of Psychiatry, Youngstown, OH 44501, and
Chairman, The Center for Behavioral Medicine, Northside Medical Center,
500 Gypsy Lane, P.O. Box 240 Youngstown, OH 44501  330-740-3621
rwalton193@...

"Seizure and mania after high intake of aspartame," 1986,
Psychosomatics, 27: 218-20:

An age 54 woman with 20 years of depression had been stable for 11
years with medication.  She had a grand mal seizure, followed by mania,
insomnia, flight of ideas, and irritability.  A brief hospitalization
and CT scan found no apparent cause. After three weeks, this led to
psychiatric hospitalization.  Two days later, it was found that during
the several weeks before the seizure and onset of mania, she had
started using aspartame in place of sugar in her iced tea, a gallon
daily.  Four days later, the mania subsided, and 13 months later she
continued to function well, and enjoying her large amounts of iced tea,
with sugar, not aspartame.

"The possible role of aspartame in seizure induction," 1987,
Proceedings of  the First International Conference on Phenylalanine and
the Brain, Wortman, RJ, Walker E (eds.), Center for Brain Sciences and
Metabolism Charitable Trust, Cambridge, England:

Nine cases, ages 19 to 91, briefly summarized:  "Case 4: A 61 year-old
woman had been in excellent health until she began consuming an average
of half a gallon per day of sugar-free beverages prepared with "Crystal
Light" mixes.  She experienced the onset of headaches, in the absence
of a previous headache history. After three months of daily headaches,
she experienced a generalized seizure and was hospitalized.  CAT scan
and EEG were normal.  After discontinuing the use of all
aspartame-containing products, she has been headache- and
seizure-free."

To recapitulate this brief summary of a stong minority opinion amongst
highly trained, experienced, competent, and published physicians:

Dr. George R. Schwartz, M.D.
Health Press   hlthprs@...   505-982-9373
http://www.healthpress.com/in-bad-taste.html
"In Bad Taste: The MSG Symptom Complex"  drgschwartz@...

Dr. Schwartz is a magna cum laude graduate of Downstate Medical Center,
NY, board certified in two specialties, and has extensive clinical
experience.  He is a founding member of the American Trauma Society, a
charter member of the American College of Emergency Physicians and a
Founding Member and first Secretary of the American Academy of
Emergency Medicine.

Dr. Schwartz has written extensively regarding food poisonings and food
toxicology and has served as an expert in many legal cases involving
chemistry, toxicology, and forensic medicine.  In addition he has helped
to establish two regional poison control centers.  He is the
author/editor of nine books and more than 175 articles, chapters and
scientific papers.  This includes a comprehensive textbook of Emergency
Medicine now in its fourth edition.

Dr. Schwartz has a special interest in aviation and flying safety and
has been designated by the FAA Regional Flight Surgeon as an Aviation
Medical Examiner.

>From his 1999 paper, accepted for publication, "NutraSweet and Brain
and Other Cancers":

"Mechanism of Action:
Nutrasweet (aspartame) is composed of linkages of aspartic acid,
phenylalanine and methanol.  The aspartic acid acts as a
neuroexcitatory agent.(1)  When NutraSweet is digested, it yields 10%
methanol (wood alcohol).(2) The wood alcohol (methanol) is widely
distributed throughout the body including brain, muscle, fat and nervous
tissue.(3)  It is then metabolized to formaldehyde which enters the
cells and binds to the proteins and DNA (the genetic material).(4)"

Mark D. Gold, not a trained medical professional, maintains a website
that contains intelligent, lucid, thorough, and reasonably fair
information and analysis, including about 250 pages of personal reports
from posts on the Internet:

Aspartame Toxicity Information Center
http://www.HolisticMed.com/aspartame/
mgold@...
35 Inman St., Cambridge, MA 02139   617-497-7843

The primary treatment and preventive is simple: discontinue all
aspartame.  Royal Crown Diet Rite Cola uses only sucralose.
Club soda may be mixed with juices to make delicious drinks, for
instance pomegranate juice on ice with a touch of lemon.

Anyone who daily drinks many cans of diet soda may be unpredictably
affected after months and years of exposure.  I found the following
report from a competent person in Brazil today alarming:

Message: 15   on aspartame@onelist.com   discussion group
    Date: Wed, 5 May 1999 17:29:44 -0300
    From: Beatriz Medina - Diagramacao - O GLOBO <Beatriz@...>
Subject: Clinton & Diet Coke

At this very moment in the newspaper where I work the editor of
international news asked me to choose a photograph of Clinton at the
Ramstein Air Base, in Germany, with American soldiers, to illustrate his
cover article. Well, among 101 Clinton photographs sent by international
agencies today there were 14 of Clinton dining with the soldiers.
Clinton was holding or drinking a can of Diet Coke in 13 of these 14
photographs. Of course I chose the 14th.

Hugs to all,
Beatriz Medina.
Rio de Janeiro, Brazil

Message: 18  on   aspartame@onelist.com   discussion group
    Date: Wed, 5 May 1999 14:21:17 -0700
    From: "Carol Guilford" <Carolg8@...>
Subject: Re: [rosacea] Bashing Bill

Dear Rosacea e-group

The letters I mentioned sent to the White House were to warn Bill
Clinton, not to embarrass him.  Why would anyone do that. It's not a
funny malady, is it?

Unfortunately the face is the thing people look at when they talk to
you.  Inner beauty takes a while to discern.

I didn't post the Nancy Markle article.  And I don't know who did.
I am glad you all have the information.  That post was plagiarized
from Betty Martini-- there is no Nancy Markle, but it went around the
world and it is the reason the a-------e victims are beginning to find
out what is wrong with them.

I am leaving this list.  99 percent of the posts here concern topical
facial remedies for rosacea without much curiosity about what is
causing this terrible facial disease in yourself or others.  And that
is fine, but not what I am interested in.  I am interested in seeing
that whatever is causing this disease is found before everyone has it.
You are the pioneers.   My only guidance is that you should really be
tough on your derms, as you call them.  Why aren't they finding out?
Like the internists who diagnose MS instead of you know what-- that is
how they make their money... Rosacea is now NO. 5 skin disease and
climbing.

One last thing.  Suzanne-- I did read a case that described exactly the
rushing feeling through the body.  And a feeling of being poisoned.
This person was detoxing.  And y'all know what from.

Oh, one last, last thing. When an additive is in more than 9,000
products it's kind of hard to stay away from it.  Don't be too sure,
Diane you haven't been ingesting wood alcohol.  It's in every OTC
pain killer on the market.  Formic acid labeled as methylcellulose.
That's the extra strength Wood alcohol to take away the pain.

The latest products with that abominable name, is now in Centrum
Vitamins and Tylenol Jr.,  Oh, and light chocolate syrup.

Formic acid the breakdown of methanol is in guacamole dip, paint
stripper,  wallpaper backing, and used as a  pesticide sprayed on
vegetables.  No, the farmers aren't choosy.  They use propylene
alcohol, too.  Those little bugs just don't like alcohol.
Methycellulose (formic acid) is used to fumigate larvae from tobacco,
dried fruit and dried nuts.  So careful,  Denial could cause flushing,
dry eyes, and pustules.

Whew.

CG

Carol

-----Original Message-----
From: RHMACRAE@... <RHMACRAE@...>
To: rosacea-support@egroups.com <rosacea-support@egroups.com>
Date: Wednesday, May 05, 1999 9:26 AM
Subject: [rosacea] Bashing Bill

Carol wrote:
His face started flushing, he looked zoned out (as Monica described
him to Linda Tripp--"I think he's on drugs") and then toward the end
of the four hours, he became loquacious as alcohol will do to one.
However, remember this is not drinking alcohol, but methanol (wood
alcohol) thus his complaints about his vision and his memory.

I can tell you hundreds of calls, letters, faxes and e-mails have been
sent to the White House to tell him about his condition.

Hi
I felt very sad when I read the attack on Bill Clinton and his rosacea.
I quess that is how some people view me and my red nose.  I can only
imagine how I would feel if I started getting letters telling me I had
a red nose -- as if I hadn't noticed and accused me of abusing my body.
One thing I love about this group is the way we share our highs and
lows in the knowledge that we are not judged but understood.  I don't
think any rosacean in or out of the group should be talked about in
such a derogatory fashion.
Bye
Harriet

I hope this information is both interesting and useful, even though,
hopefuly, it may not be relevant to your current responsibilities.

Regards,  Rich Murray
****************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1018
aspartame toxicity coverup increases danger of corporate meltdown:
Michael C. Carakostas of Coca-Cola: Murray 8.11.3 rmforall
http://www.isrtp.org/new_members/members1.htm
The International Society of Regulatory Toxicology and Pharmacology
Carakostas, Michael C., DVM, PhD Director/Scientific & Regulatory
Affairs   The Coca-Cola Company PO Drawer 1734 Atlanta, GA 30301
T. 404/676-4234   F. 404/676-7166   E-mail: mcarakostas@...
http://www2.coca-cola.com/ourcompany/columns_aspartame.html  [photo]
Aspartame: The world agrees it's safe   By Michael Carakostas, DVM, PhD
Director, Scientific and Regulatory Affairs, Coca-Cola

It is commendable that Carakostas mentions the core problem, albeit
disparagingly:   "During digestion, aspartame yields a very small amount
of methanol-- as do many other food substances. The body converts this
methanol to formaldehyde, which is instantly converted to formate.
Formate is quickly eliminated as carbon dioxide and water."

Plenty of evidence in the mainstream scientific literature since 1973
shows that as much as 30% of the formaldehyde is retained in the body as
toxic, cumulative adducts to the DNA, RNA, and proteins in all cells and
tissues, leading to pointed reports by informed doctors and experts.
Clearly, there are no safe levels for chronic, low-level formaldehyde
exposure.  If just 10% of the methanol from six cans of diet soda is
retained in the body as toxic products of formaldehyde and formic acid,
that is sixty times the EPA limit for allowable formaldehyde from daily
drinking water.
********************************************************

research on aspartame (methanol, formaldehyde) toxicity:
Murray 3.23.4 rmforall

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.

http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 751 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1065 posts in a public searchable archive  120 members

http://groups.yahoo.com/group/aspartame/messages 774 with 16,660 posts

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research 7.31.2 rmforall

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 7.10.0 rmforall

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9: rmforall

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall  EU Scientific Committee on Food

http://groups.yahoo.com/group/aspartameNM/message/841
RTM: Merisant Co., MSD Capital, Dell Computer Corp., NutraSweet Co.,
JW Childs Assc.: aspartame-neotame toxicity 7.10.2 rmforall

Many scientific studies and case histories report:  * headaches
* many body and joint pains (or burning, tingling, tremors, twitching,
spasms, cramps, stiffness, numbness, difficulty swallowing)
*  fever, fatigue, swollen glands  * "mind fog", "feel unreal", poor
memory, confusion, anxiety, irritability, depression, mania, insomnia,
dizziness, slurred speech, sexual problems,  poor vision, hearing
(deafness, tinnitus), or taste  * red face, itching, rashes, hair loss,
burning eyes or throat, dry eyes or mouth, mouth sores, burning tongue
* obesity, bloating, edema, anorexia, poor appetite or excessive hunger
or thirst    * breathing problems, shortness of breath * nausea,
diarrhea or constipation  * coldness  * sweating  * racing heart, low or
high blood pressure, erratic blood sugar levels  * hypothryroidism or
hyperthyroidism  * seizures  * birth defects  * brain cancers
* addiction  * aggrivates diabetes, autism, allergies, lupus, ADHD,
fibromyalgia, chronic fatigue syndrome, multiple chemical sensitivity,
multiple sclerosis, and interstitial cystitis (bladder pain).
***********************************************************

http://groups.yahoo.com/group/aspartameNM/message/1064
Diet Soda [aspartame] Dangerous? Shari Lieberman, The O'Reilly Factor
3.19.4: Murray 3.23.4 rmforall

http://www.foxnews.com/story/0,2933,114880,00.html    oreilly@...

Dr. Shari Lieberman <drshari@...>     http://www.drshari.net

Diet Soda Dangerous? Monday, March 22, 2004

This is a partial transcript from "The O'Reilly Factor," March 19, 2004 that
has been edited for clarity.

Watch The O'Reilly Factor weeknights at 8 p.m. and 11 p.m. ET and listen to
the Radio Factor!

BILL O'REILLY, HOST: In the "Back of the Book" Segment tonight, Americans
drink billions of gallons of diet soda a year. It's incredible how much we
consume. And some believe millions of Americans are addicted to the stuff.
They have to have it.

With us now is Dr. Shari Lieberman, a certified nutrition specialist here in
New York City.

All right. So it's -- 10 billion cases of soda sold every year in the USA,
and 30 percent of that, approximately, is diet soda, and I know people who
walk around all day long drinking diet soda. What is that all about?

SHARI LIEBERMAN, PH.D., CERTIFIED NUTRITION SPECIALIST:
It's unbelievable. It is such an addicting substance. You have both the
aspartame, the NutraSweet, combined with the caffeine. You're basically
getting a rush all day. It actually messes with your brain chemicals, Bill.

O'REILLY: Does it really?

LIEBERMAN: It really does. You know, aspartic acid actually makes what we
call excitatory neurotransmitters. Imagine we have a balance of ones that
calm us down and ones that hype us up.

So, if you're drinking something that's going to make the ones that are
excitatory or making us hyper all day long, that's why there are so many
side effects associated with NutraSweet, such as irritability and anxiety.

I mean people are basically getting a rush all day from drinking this.

O'REILLY: OK. So, if you're drinking diet soda all day long or, say, you're
drinking, you know, 48 ounces, 50 ounces a day, which a lot of people do...

LIEBERMAN: They do.

O'REILLY: ... you are basically -- it's an upper.

LIEBERMAN: It's an upper. Exactly. And guess what happens when you run out
of it? It's a crasher...

O'REILLY: Is that right?

LIEBERMAN: ... and then you need an upper.

O'REILLY: You feel bad after it.

Now is this physically addicting, do you believe, or is it psychological?

LIEBERMAN: I believe it's physically addicting. You know, we know that
caffeine is. So you've got a ton of caffeine in the diet sodas. Then you
actually have a substance that's affecting neurotransmitters. So they're
really getting a double whammy, and, of course, we're talking about people
that are drinking it all day long.

O'REILLY: Yes, and they think that, well, I can drink it all day long
because there's no calories in it, I'm not going to get fat. Go ahead.

LIEBERMAN: I have to tell you something about that. If you look at the
research, people that drink diet sodas are oftentimes eating more calories
than people drinking regular sodas.

O'REILLY: But they're eating them.

LIEBERMAN: It actually increases...

O'REILLY: You know, that's -- they're eating.

LIEBERMAN: It seems to increase...

O'REILLY: You can't get fat drinking diet soda.

LIEBERMAN: It's not that you get fat, Bill. I think it's the...

O'REILLY: Bloated.

LIEBERMAN: ... taste of the sweet. It keeps you so addicted. They seem to
eat more carbohydrates throughout the day when they're drinking diet soda.
Go figure.

O'REILLY: What other physical things -- if you're consuming a lot of diet
soda, what happens to your body?

LIEBERMAN: Well, you also can get a certain amount of methanol, which is the
more toxic alcohol. That's a byproduct of NutraSweet and aspartame, if
you're drinking a lot of it, and that's a wood alcohol that's actually
rather toxic and can cause some problems as well. So you have a substance
that, when you're taking in really large amounts, is going to affect your
chemistry, your brain chemistry, your...

O'REILLY: Your body chemistry and...

LIEBERMAN: Exactly. Your body chemistry.

O'REILLY: OK. Now there are no warnings on any of the soda labels, and
nobody says any of this. But, you know, I -- and I wanted to do the story
because, anecdotally, I've seen people, you know, in the office here and all
of that, drink diet soda after diet soda after diet soda.

LIEBERMAN: Well, who did my makeup today actually said to me she's drinking
a ton of diet soda and is suffering from migraines. There are reports of
migraines and fibromyalgia and certain illnesses disappearing when people go
off diet sodas. So, I mean, there is a relationship between taking in a lot
of this stuff -- we're not talking about the occasional user.

O'REILLY: No.

LIEBERMAN: But if -- you know, once again, you've got these excited neurons
in your head, and it is related to migraines and fibromyalgia and a number
of other illnesses that have been shown to go away.

O'REILLY: Right. And it doesn't do any -- your teeth any good either?

LIEBERMAN: It really -- it doesn't protect your teeth like Xylitol and some
of the other sweeteners.

O'REILLY: All right, Doctor. I knew drinking 50 ounces of that stuff wasn't
good.

LIEBERMAN: You were right, Bill.

O'REILLY: You know, one Dr. Pepper once in a while, fine, but, you know,
leave the six-pack home.

Content and Programming Copyright 2004 Fox News Network, Inc. ALL RIGHTS
RESERVED. Transcription Copyright 2004 eMediaMillWorks, Inc. (f/k/a Federal
Document Clearing House, Inc.), which takes sole responsibility for the
accuracy of the transcription.
ALL RIGHTS RESERVED. No license is granted to the user of this material
except for the user's personal or internal use and, in such case, only one
copy may be printed, nor shall user use any material for commercial purposes
or in any fashion that may infringe upon Fox News Network, Inc.'s and
eMediaMillWorks, Inc.'s copyrights or other proprietary rights or interests
in the material. This is not a legal transcript for purposes of litigation.
***************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1059
foxnews.com, The O'Reilly Factor, Shari Lieberman, diet soft drinks
(aspartame), Friday March 19 2004: Mike: Martini: Murray 3.21.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1063
positive response to Lieberman on The O'Reilly Factor:
Lieberman: Murray 3.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.

http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 751 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1064 posts in a public searchable archive  120 members

http://groups.yahoo.com/group/aspartame/messages 774 with 16,660 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
( becomes formaldehyde in body ):  EU Scientific Committee on Foods 7.12.1:
Murray 1.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 1.17.2 rmforall
Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is
often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome
for two to 17 years are described.
All had undergone multiple treatment
modalities with limited success. All had complete, or nearly complete,
resolution of their symptoms within months after eliminating monosodium
glutamate (MSG) or MSG plus aspartame from their diet.
All patients were women with multiple comorbidities
prior to elimination of MSG.
All have had recurrence of symptoms whenever MSG is ingested.

Siegfried O. Schmidt, MD  Asst. Clinical Prof.  siggy@...
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
352-376-5071

http://groups.yahoo.com/group/aspartameNM/message/846
RTM: aspartame in Merck Maxalt-MLT worsens migraine,
AstraZeneca Zomig, Eli Lilly Zyprexa,
J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab,
Pfizer Cool Mint Listerine Pocketpaks 7.16.2 rmforall
Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB  Headache 2001 Oct; 41(9): 899-901.
[Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg.]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology   newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research   RLipton@...

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches.
Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA.   neurotulsa@...
Aspartame, a popular dietetic sweetener, may provoke headache in some
susceptible individuals. Herein, we describe three cases of young women
with migraine who reported their headaches could be provoked by chewing
gum sweetened with aspartame. [6-8 mg aspartame per stick chewing gum]

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M  ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo.  Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male)  alemany@...

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ].  Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@...    919-684-3303, 660-5657
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall ]

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Formaldehyde was administered for 104 weeks in drinking water supplied
ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
rats beginning at six weeks of age at concentrations of 2,500, 1,500,
500, 250, 50, or 0 mg/L.
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase in total
malignant tumors in the treated groups and showed specific carcinogenic
effects on various organs and tissues.  PMID: 12562630

Surely the authors deliberately emphasized that aspartame is well-known
to be a source of formaldehyde, which is an extremely potent, cumulative
toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested
aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No.      No. of Bioassays  Species    No.       Route of Exposure
108.  "Coca-Cola"     4     Rat       1,999    Ingestion, Transplantal Route
109.  "Pepsi-Cola"    1      Rat          400         Ingestion
110.   Sucrose          1      Rat          400         Ingestion
111.   Caffeine          1      Rat          800         Ingestion
112.   Aspartame      1      Rat       1,800         Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]

http://www.dorway.com/tldaddic.html  5-page review
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter  2000 Jan;  HJRobertsMD@...
http://www.sunsentpress.com/    sunsentpress@...
Sunshine Sentinel Press  P.O.Box 17799  West Palm Beach, FL 33416
800-814-9800 561-588-7628 561-547-8008 fax

http://groups.yahoo.com/group/aspartameNM/message/669
1038-page medical text   "Aspartame Disease: An Ignored Epidemic"
published May 30  2001    $ 60.00 postpaid    data from 1200 cases
available at  http://www.amazon.com
over 600 references from standard medical research
*****************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1063
positive response to Lieberman on The O'Reilly Factor:
Lieberman: Murray 3.22.4 rmforall

The O'Reilly Factor oreilly@...

From: "Dr. Shari Lieberman" <drshari@...>
To: "Rich Murray" <rmforall@...>
Subject: Re: research on aspartame (methanol, formaldehyde) toxicity: Murray
3.21.4 rmforall
Date: Sunday, March 21, 2004 4:07 PM

Hi Rich:

That was so nice of you to send me all this stuff!  I really
appreciate it.  I am aware of the formaldehyde issue as well and the
increase in brain cancer incidence.  These are great references and I
will check them out and save them as well.

Regards,  Dr Shari Lieberman
*****************************************************************

From: "Dr. Shari Lieberman" <drshari@...>
To: "Rich Murray" <rmforall@...>
Subject: Re: can you send me your O'Reilly transcript?: Lieberman: Murray
3.21.4
Date: Monday, March 22, 2004 10:41 AM

Hi Rich:

I received so many emails you would be shocked. All of them were
positive thanking me - I couldn't believe I didn't get any hate mail!
Bill O'Reilly was really into it - I could have mentioned the formaldehyde
issue and even the increase in glioblastoma - but I though for a
short segment it was better to focus on the neurotransmitter issue.
If I covered too much - it would have been confusing.  Let me ask if
they can get me a transcript of the show.  And keep me posted on your work.

Warmest regards,  Dr Shari Lieberman
******************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall
******************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1062
individual sensitivity to additives, primrose oil seizure hazard, DNA
damage: Wild: Murray 3.22.4

From: "Charles T. Wild" <ctw1940@...>
To: "Rich Murray" <rmforall@...>
Cc: "Charles T. Wild" <ctw1940@...>
Subject: Re: research on aspartame (methanol, formaldehyde) toxicity: Murray
3.21.4 rmforall
Date: Monday, March 22, 2004 8:27 AM

Rich Murray,

Here are a few thoughts about the topic you bring up.

You may like some of the following comments, dislike or hate some of the
following comments, or have no opinion on some of the following comments.

You may or may not know this but I am extremely chemically sensitive to a
few food additives including FD&C Yellow Food Color No. 5 (tartrazine),
sodium saccharin, and aspartame (incomplete list).

Yes, aspartame is a food additive/ingredient which deserves far better
labeling when it is a part of food products/drug products.  That's my view.

Apparently there is a small group of persons who are extremely chemically
sensitive to a number of food additives/food ingredients (including myself).

Part of the solution in an imperfect world is full ingredient disclosure
labeling (my view) and perhaps a rotating series of written cautions ~
similar to what is put onto tobacco/nicotine products perhaps so that those
persons who are extremely chemically sensitive to a number of food
additives/ingredients are better informed and can make better choices for
themselves.

Making better choices for oneself (democracy - America) is quite different
than forcing the same choice on everyone (tyranny - the King of England ) so
to speak.

http://www.archives.gov/national_archives_experience/declaration_transcript.html

Persons can voluntarily choose to ban food products/drug products which
contain aspartame from their own lives by making better choices for
themselves, that is, by shopping at organic, natural food stores or at
regular supermarkets and ~  being very careful in purchasing products there
which are additive-free.

Regarding coffee, caffeine-products - there are three viewpoints:

Some persons (like myself find coffee/caffeine products beneficial);  others
find them neutral (and consume them for the taste);  and still others find
them unwanted and choose to avoid them.

http://web.sfn.org/content/Publications/BrainBriefings/adenosine.html

Effects of caffeine on cognitive, psychomotor, and affective performance of
children with Attention-Deficit/Hyperactivity Disorder.
M. Roth Leon

Studies examining caffeine's effects on cognitive, psychomotor, and
affective functioning of children with ADHD were reviewed. For children with
ADHD, caffeine was more effective than no treatment in decreasing
impulsivity, aggression, and parents' and teachers' perceptions of
children's symptom severity, and more effective than placebo in decreasing
hyperactivity and teachers' perceptions of children's symptom severity, and
in improving executive functioning/planning. Methylphenidate...

http://www.mhs.com/jad/abstracts/v4n1.htm

It is a major error (my view) to promote the false idea that the same food
item (such as alcohol, nicotine, etc.) will always produce the same result
in everyone.  That doesn't match the real world at all.

Many persons in the world enjoy peanuts/peanut butter yet every year in the
United States a small number of persons actual die from adverse reactions to
the natural food called organic peanuts.

Many persons can consume the natural product evening primrose oil yet that
same natural product apparently can lower the seizure threshold for some of
those with epilepsy.

Evening Primrose Oil  (and Gamolenic Acid)

(Gamolenic Acid: provided by oil from the evening primrose oil seed)

The publication British National Formulary advises caution in prescribing
this treatment to people with a history of epilepsy. Anecdotal evidence from
callers to the Epilepsy Helpline also indicates that taking Evening Primrose
Oil (EPO) may make someone with a low epileptic threshold more likely to
experience seizures.

http://www.epilepsy.org.uk/info/epo.html

You're absolutely right in saying that aspartame can be a major item of
concern for some persons in society/in the world;  at the same time,
apparently aspartame and other food ingredients for some reason or another
are not much of a concern for many people.

People have the right to adopt the kind of nutrition approach they want (my
view);  forcing a certain nutritional approach on everyone will backfire in
the short, medium, and long run due to ~ human nature (my view).

Personally, in my own life, have found that the Jack LaLanne Power Juicer as
well as the Vita-Mix blender have been useful tools for me in moving towards
a whole food, additive-free nutrition program.

Best wishes,  Charles Thomas Wild

http://health.groups.yahoo.com/group/Tartrazine_and_ADHD/

http://health.groups.yahoo.com/group/C_Thomas_Wild_ADHD_ADD_Autobiography/

http://www.aacap.org/clinical/Adhdsum.htm

http://health.groups.yahoo.com/group/ADHD_Bulletin_Board/
****************************************************************************
*******************

March 22 2004  Hello Charles Wild, Thank you for your thoughtful, informed
comments.  I'll share them on my groups.

Aspartame reactors need to be aware of the seizure hazards of  Evening
Primrose Oil  (and  its Gamolenic Acid).

These two very long posts describe some of the biochemical mechanisms that
can produce Multiple Chemical Sensitivity, as well as the possibility that
low levels of some toxins can be beneficial for certain people.

http://groups.yahoo.com/group/aspartameNM/message/1055
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 3.11.4

http://groups.yahoo.com/group/aspartameNM/message/1056
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall

It is interesting that this study found DNA damage in mice from tartrazine,
sodium saccharine, and aspartame (aspartame results were almost significant,
with just 4 mice):

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

Mutat Res 2002 Aug 26; 519(1-2): 103-19
The comet assay with 8 mouse organs: results with 39 currently used food
additives.
Sasaki YF, Kawaguchi S, Kamaya A, Ohshita M, Kabasawa K, Iwama K,
Taniguchi K, Tsuda S.
Laboratory of Genotoxicity, Faculty of Chemical and Biological
Engineering, Hachinohe National College of Technology,
Tamonoki Uwanotai 16-1, Aomori 039-1192, Japan.
yfsasaki-c@...  s.tsuda@...

We determined the genotoxicity of 39 chemicals currently in use as food
additives. They fell into six categories-dyes, color fixatives and
preservatives, preservatives, antioxidants, fungicides, and sweeteners.

We tested groups of four male ddY mice once orally with each additive at
up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet
assay on the glandular stomach, colon, liver, kidney, urinary bladder,
lung, brain, and bone marrow 3 and 24 h after treatment.

Of all the additives, dyes were the most genotoxic. Amaranth, Allura
Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal
induced dose-related DNA damage in the glandular stomach, colon, and/or
urinary bladder.

All seven dyes induced DNA damage in the gastrointestinal organs at a
low dose (10 or 100mg/kg).

Two antioxidants (butylated hydroxyanisole (BHA) and butylated
hydroxytoluene (BHT)), three fungicides (biphenyl, sodium
o-phenylphenol, and thiabendazole), and four sweeteners (sodium
cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA
damage in gastrointestinal organs.

Based on these results, we believe that more extensive assessment of
food additives in current use is warranted.  PMID: 12160896

Toxicol Sci 2001 May;61(1):92-9
DNA damage induced by red food dyes orally administered to pregnant
and male mice.
Tsuda S, Murakami M, Matsusaka N, Kano K, Taniguchi K, Sasaki YF.

Laboratory of Veterinary Public Health, Department of Veterinary
Medicine, Faculty of Agriculture, Iwate University, Ueda 3-18-8,
Morioka, Iwate 020-8550, Japan.  s.tsuda@...

We determined the genotoxicity of synthetic red tar dyes currently used
as food color additives in many countries, including JAPAN: For the
preliminary assessment, we treated groups of 4 pregnant mice
(gestational day 11) once orally at the limit dose (2000 mg/kg) of
amaranth (food red No. 2), allura red (food red No. 40), or acid red
(food red No. 106), and we sampled brain, lung, liver, kidney, glandular
stomach, colon, urinary bladder, and embryo 3, 6, and 24 h after
treatment.

We used the comet (alkaline single cell gel electrophoresis) assay to
measure DNA damage. The assay was positive in the colon 3 h after the
administration of amaranth and allura red and weakly positive in the
lung 6 h after the administration of amaranth.

Acid red did not induce DNA damage in any sample at any sampling time.

None of the dyes damaged DNA in other organs or the embryo.

We then tested male mice with amaranth, allura red, and a related
color additive, new coccine (food red No. 18). The 3 dyes induced DNA
damage in the colon starting at 10 mg/kg.

Twenty ml/kg of soaking liquid from commercial red ginger pickles, which
contained 6.5 mg/10 ml of new coccine, induced DNA damage in colon,
glandular stomach, and bladder.

The potencies were compared to those of other rodent carcinogens. The
rodent hepatocarcinogen p-dimethylaminoazobenzene induced colon DNA
damage at 1 mg/kg, whereas it damaged liver DNA only at 500 mg/kg.

Although 1 mg/kg of N-nitrosodimethylamine induced DNA damage in liver
and bladder, it did not induce colon DNA damage. N-nitrosodiethylamine
at 14 mg/kg did not induce DNA damage in any organs examined. Because
the 3 azo additives we examined induced colon DNA damage at a very low
dose, more extensive assessment of azo additives is warranted.
PMID: 11294979

In mutual service,  Rich Murray

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.

http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1063 posts in a public searchable archive  120 members

http://groups.yahoo.com/group/aspartame/messages 774 with 16,660 posts

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]
*****************************************************************

Food Additives and ADHD - a very rare, true story which calls for
full ingredient disclosure labeling of foods and drugs so that those
persons who are extremely chemically sensitive to a few food
additives/ingredients are better informed and can make better
choices for themselves.

http://health.groups.yahoo.com/group/Tartrazine_and_ADHD/

Tartrazine (FD&C Yellow Food Color No. 5) and ADHD is a discussion group for the
topic of how the food color additive Tartrazine (FD&C Yellow Food Color No. 5)
can occasionally impact the process of human cognition including the ability to
pay attention, memorize, to see, to hear and so on including those with ADHD -
ADD - Attention Deficit, epilepsy, or other related known lifelong neurological
challenges.

The founder of this group is Charles Thomas Wild, an adult with ADHD -
Inattentive Type - who is known to be extremely chemically sensitive to
Tartrazine (FD&C Yellow Food Color No. 5) and several other food additives
including the sweetener, sodium saccharin, and the mild stimulant/alerting agent
coffee/caffeine compounds. His doctor is Anita Uhl Brothers, M.D., of Berkeley,
California.

Please consider joining.
********************************************************************************\
**

http://groups.yahoo.com/group/aspartameNM/message/1060
Barbara Ferguson Kennedy: Arab News 6.4.1 article against aspartame:
Murray 3.21.4 rmforall

""I also write an 'alternative health' column for Arab News a pan-Arab
English-language daily, for which I am their Washington Correspondent. Most
stories are well received, but my story condemning Aspartame created
shockwaves we were not prepared for.

'You've been covering Middle East politics for years, and I've never had any
complaints about your stories,' my editor hollered into the phone after the
story was published. 'But we've received dozens of complaints about your
story on Aspartame. What in the hell is Aspartame?' he yelled. Diabetics
were furious that I suggested Aspartame was not their friend."

" Other additives, like monosodium glutamate (MSG) and aspartame, are used
without warnings, but have been known to cause problems ranging from
headaches and diarrhea to confusion, memory loss, and seizures."

[ http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall ]

http://www.findarticles.com/cf_0/m0JMQ/4_24/80899043/p1/article.jhtml

Conversations. (natural hygiene, the National Health Association, healthy
lifestyle)  Health Science, Fall, 2001

This third of a three-part series reports conversations with each of the
current Members of the Board of Directors. "Conversations" continues the
Board's sharing, in their own words, their ideas on Natural Hygiene, the
historical framework of the National Health Association, and the importance
of a healthy lifestyle and a healthy diet. The underlying philosophy and
principles of the Association were discussed, as were implications for the
future of the Association. Board Members shared how they became involved
with NHA, the value of belonging to this membership organization, and their
perceptions about the future of the Association. As in the previous
Conversations with Board Members [Spring and Summer 2001 Health Science),
Board Members here share their candid thoughts and observations.

Barbara Ferguson Kennedy
Barbara Ferguson Kennedy was elected to the Board of Directors in 2000. She
is a Washington journalist and lives with her husband in Virginia.

"My husband, Tim, and I have been total vegetarians for five years-a
decision we made after it dawned on us that too many of our family members
had been lost to cancer; and the realization that food, and the environment,
have a substantial influence on health.

"Unlike many who discovered NHA themselves, I'm fortunate to have been
hand-led to the organization. My uncle, Wilson Brownell, has been a member
of NHA for many years, and was a great admirer of Herbert Shelton, the
leader of Natural Hygiene.

"My path to health began in Paris, where I was based as a journalist for 16
years. The French are quite strict about the quality of their food. For
example, preservatives in bread are absolutely forbidden, and for decades
fruit and vegetable stands have been required to indicate whether foods are
organic, 'wax sprayed' or treated with pesticides.

"While I was there, French health organizations made public that young men
were developing 'breasts' because of growth hormones in meat and chicken.
This information put more than a few people, including myself, off flesh.

"From Paris I was transferred to London for two years. Obsession over food
freshness is not a national pastime as in France, but is not dealt with as
carelessly as in America.

"I moved to Washington in 1991. Being a journalist, and a vegetarian, always
makes for interesting conversation at cocktail parties. Some people view
you, or vegetarianism, with vague curiosity. Others back up a few steps as
if the 'state-of-being' is contagious. Journalists, like anyone else, are
very comfortable with conformity. Only occasionally will someone ask me
questions.

"Many people wonder how I manage overseas. The airlines are behind the
times, of course, but should be encouraged for offering 'vegan,' 'ovo-lacto'
and 'vegetarian' meals. No matter what international airlines I fly, they
all seem to share the same single recipe for my 'vegan' meal preference:
Cucumber sandwiches! But I always arrive feeling much more refreshed than my
fellow passengers who ate the on-board cholesterol-clogging meals.

"As a specialist in Middle Eastem affairs, the Washington Times sends me to
the region a couple of times a year. Being a vegetarian in the Middle East
is easy. There are copious mezza salads,' an infinite assortment of
vegetable courses, and fresh fruits.

"Back home, I still struggle over what to serve my guests. As both Tim and I
are journalists, 'schmoozing' is important, and so is entertaining.

"Being a vegetarian journalist in Washington does have its perks. Washington
is notorious as a city that doesn't like to talk to journalists; but PETA
loves to talk to me, so does the Physicians Committee on Responsible
Medicine, and the Worldwatch Institute, just to name a few.

"I also write an 'alternative health' column for Arab News a pan-Arab
English-language daily, for which I am their Washington Correspondent. Most
stories are well received, but my story condemning Aspartame created
shockwaves we were not prepared for.

'You've been covering Middle East politics for years, and I've never had any
complaints about your stories,' my editor hollered into the phone after the
story was published. 'But we've received dozens of complaints about your
story on Aspartame. What in the hell is Aspartame?' he yelled. Diabetics
were furious that I suggested Aspartame was not their friend.

"I hope this summary gives you an idea of my enthusiasm for health and my
membership at NHA. I am committed to promoting the principles of our
organization and am truly honored to serve our wonderful organization - and
all of you."
*************************************************************

http://www.anhs.org/
The National Health Association
P.O. Box 30630  Tampa, FL 33630
Phone: 813.855.6607   Fax: 813.855.8052   info@...

http://www.anhs.org/health.htm  Health Science magazine
**************************************************************

http://www.findarticles.com/PI/index.jhtml?pre=aspartame

LookSmart's FindArticles - search and read 3.5 million articles from over
700 publications.

Lists full text of 358 articles that mention "aspartame".
**************************************************************

http://www.arabnews.com/     arabnews@...
Editor in Chief Mr. Khaled Al-Maeena   almaeena@...
Barbara Ferguson arabnews1@...
P. K. Muhammad  opinion@...

http://www.arabnews.com/?page=9&section=0&article=2428&d=4&m=6&y=2001

Processed food: What is a 'natural flavor'?
By Barbara Ferguson, Arab News Correspondent

WASHINGTON, 4 June 2001 - Buy it in a box. Buy it in a can. Buy it in a
plastic container. Voila! Instant dinner. Pre-cooked and ready to eat, just
add heat. Somewhere in the race for convenience food, Americans have
abandoned one of the most basic human activities - preparing food. Ninety
percent of the money Americans spend on food is used to buy processed food,
according to the recently published book, Fast Food Nation.

Today, fresh, whole food in the supermarket is passed by for convenience
food offered in jars, cans, boxes, plastics and frozen food containers
promising delicious dinners in seconds.

You may have wondered, at least once, how a dinner cooked months ago, frozen
and stored in a box, could taste any good? The answer lies in those
interesting 'natural' and 'artificial' flavorings, the small but potent
ingredients in nearly all processed foods. There is a limit to what you can
do to food and still have it taste good. Food processors often use high
temperature, flavor-draining methods to create shelf-stable foods. A factory
production line that flash freezes, boils and/or dehydrates huge quantities
of foodstuff cannot duplicate the complex flavor of fresh food. But a close
replica of that complex flavor can be produced in labs where men and women
in white coats carefully deconstruct the chemical constituents of flavors,
then re-create those flavors in the form of highly potent chemicals.

The results are easy to detect: Simply compare the canned chicken soup to
the homemade chicken soup. Or, compare fast food French fries to homemade
French fries. Or, fresh juice to canned juice. In all of these examples, you
are likely to taste that processed foods have an overwhelming, ever
over-stimulating, essence. When nutritionists talk about diet, they are
referring to live whole foods - unprocessed food with nothing added or taken
away. Whole foods are more healthful because they contain non-potentially
harmful ingredients. In addition, plant foods are full of hundreds of
phytochemicals that can help prevent disease and keep the body healthy.
These are our front-line defenders against cancer and free radicals. Foods
known to supply important phytochemicals include soybeans and soy products,
broccoli, citrus peels, flax, garlic, green tea, grapes, and tomatoes.

Additives are placed in foods for a number of reasons: To lengthen shelf
life; to make a food more appealing by enhancing color, texture, or taste;
to facilitate food preparation; or to otherwise make the product more
marketable.  Certain additives, like sugar, are derived from natural
sources. Other additives, like aspartame (NutraSweet), are made
synthetically. Although many additives are used in very small amounts, it
has been estimated that the average American consumes about 5 pounds of
additives per year. If you include sugar - the food-processing industry's
most used additive - the number jumps to 135pounds a year. So it doesn't
take much to understand that anyone whose diet is high in processed products
clearly consumes a significant amount of additives and artificial
ingredients.

At their best, additives and artificial ingredients simply add little or not
nutritional value to a food product. At their worst, additives pose a threat
to your health. The history of additive use includes a number of products
that were once deemed safe but later were banned or allowed to be used only
if accompanied by warnings. The artificial sweeteners cyclamate and
saccharin are just two examples of such products. Other additives, like
monosodium glutamate (MSG) and aspartame, are used without warnings, but
have been known to cause problems ranging from headaches and diarrhea to
confusion, memory loss, and seizures.

The number of food additives now in use is staggering. To learn more about
these substances, you can consult Eric Schlosser's Fast Food Nation
(Houghton Mifflin,2001 ), Michael Jacobson's Safe Food: Eating Wisely in a
Risky World, (Living Planet Press,1991 ), or Unsafe at Any Meal by Earl
Mindell (Warner Books,1986 ).

Out of curiosity, I called several food production companies to ask what was
in the "natural flavor" listed on their food product's label. No company
would was willing to share the precise components of their "natural flavor."
The customer service representatives explained, "That information is
proprietary and part of the secret recipe."  Consider this; natural flavor
is the smallest or second smallest ingredient in most of the products I
researched. The other ingredients, the main ingredients, added such a small
amount to the flavor of the product that they could be listed in full while
the components of the "natural flavor" must remain secret. Flavor is
processed out of processed food and then returned by way of chemical
distillates. Those who are observant Muslims, or vegetarians, and are
interested in making sure all the ingredients of your food are from a
non-pork or non-meat source, the "natural flavor" on a food's label will not
help you choose products that contain no pork, or meat-derived additives.
For this, one must contact the company listed on the label and ask for the
source of their natural flavor. While they may not give you the "secret
ingredients," they must give you dietary information about their "natural"
flavoring. A soy milk company explained that their natural flavoring was
"vegetarian, kosher, and did not contain MSG." A canned bean chili company
said their natural flavoring was "from a botanical sources."

What to do
. If you are interested in consuming whole and real foods, carefully reading
labels can help you make informed decisions. When in doubt regarding a
specific ingredient, many companies will specify the source of their natural
flavor.

. It is important to understand a "natural" flavor is not a spice, like
cumin, or it would be listed on the label.

. The solution to the natural flavor question, of course, is not petitioning
far-away food manufacturers or the corporate headquarters of fast food
companies. The answer is easily achievable and within reach. Tonight, walk
back into your kitchen, and cook a wholesome meal made from live, whole
foods.
**************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.

http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1060 posts in a public searchable archive  119 members

http://groups.yahoo.com/group/aspartame/messages 774 with 16,660 posts

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research 7.31.2 rmforall

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 7.10.0 rmforall

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9: rmforall

http://groups.yahoo.com/group/aspartameNM/message/927
Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Formaldehyde was administered for 104 weeks in drinking water supplied
ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
rats beginning at six weeks of age at concentrations of 2,500, 1,500,
500, 250, 50, or 0 mg/L.
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase in total
malignant tumors in the treated groups and showed specific carcinogenic
effects on various organs and tissues.  PMID: 12562630

Surely the authors deliberately emphasized that aspartame is well-known
to be a source of formaldehyde, which is an extremely potent, cumulative
toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested
aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No.      No. of Bioassays  Species    No.       Route of Exposure
108.  "Coca-Cola"     4     Rat       1,999    Ingestion, Transplantal Route
109.  "Pepsi-Cola"    1      Rat          400         Ingestion
110.   Sucrose          1      Rat          400         Ingestion
111.   Caffeine          1      Rat          800         Ingestion
112.   Aspartame      1      Rat       1,800         Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]
**************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1059
foxnews.com, The O'Reilly Factor, Shari Lieberman, diet soft drinks
(aspartame), Friday March 19 2004: Mike: Martini: Murray 3.21.4 rmforall

http://www.foxnews.com/story/0,2933,96207,00.html     oreilly@...

Guests and Topics: March 19 Friday, March 19, 2004
Tonight... "The O'Reilly Factor" is on!

Was the war with Iraq worth it? We'll have analysis as we mark one year
since the "shock and awe" in Iraq.

Plus, we'll inside information on the latest on the battle raging in
Pakistan (search) against Al Qaeda (search) and Taliban (search) forces. Are
we close to cracking their terrorist network? FNC Military Analyst, former
U.S. Army Col. David Hunt and FNC Foreign Affairs Analyst Mansoor Ijaz will
be here.

Then, do you know how some celebrities use charities to create an image?
We'll have the inside story on that, too.

And later, should you put down that diet soda? Why are so many Americans
addicted to diet soft drinks? Could they be harmful to your health? We'll
talk with nutritionist Shari Lieberman, Ph.D.

Finally, don't miss a brand new edition of our world famous "Talking Points
Memo" and "The Most Ridiculous Item of the Day."

See you in the No Spin Zone, tonight at 8 p.m. and 11 p.m. ET!
--All topics and guests subject to change.
--The Associated Press contributed to this story.
*************************************************************

From: "mavrick452003" <mavrick452003@...>
To: <aspartame@yahoogroups.com>
Subject: [Aspartame Support] COMMENT:OREILY FACTOR/QUESTION:BETTY MARTINI
Date: Saturday, March 20, 2004 11:49 AM

I watched Shari Liberman the nutrition spcialist from new york on the
O,reily factor last night.
I am very happy to see anyone speak out on aspartame but I think she failed.
she said that drinking a lot of diet soda is bad but she didn't say that
even drinking a small amount is bad.
She didn't mention all the other products that contain aspartame.
If your using the other products on top of the diet soda even if your not
drinking a lot your still getting
a lethal dossage.
I didn't see her outrage.
Bill O'reily is a very powerful and influential person who when outraged
about an issue can move mountains.
She didn't get him outraged and therfore did not recruit him into the fight.
I hate to sound so negitive but I just think this was a missed oportunity.

YOUR COMMENTS PLEASE.

QUESTION: BETTY MARTINI:
When will you be filing your class action suit.
We are all anxious to see this happen.

Thank You,  Mike, Boston,Mass
*************************************************************

From: "Dr. Betty Martini" <bettym19@...>
To: "mavrick452003" <mavrick452003@...>; <aspartame@yahoogroups.com>
Subject: Re: [Filtered] [Aspartame Support] COMMENT:OREILY
FACTOR/QUESTION:BETTY MARTINI
Date: Saturday, March 20, 2004 1:04 PM

Dear Mike,

I would rather see aspartame on the Oreilly Factor than many well known
prime time programs.  I have sent him information as well.  Its a hot
subject and this may have been a way to quickly get some information to the
public.  Millions see him and its played three times.  It was on again at
4:00 A.M.

By the fact they mentioned it all day on Fox News and left it to last tells
you they knew people would listen.  And it was very short.  I think they
got out a few good things, addiction, craving of carbohydrates,
fibromyalgia, headache and getting well once off of it.  That little bit to
millions helped a lot because most people with those problems will now do a
search on the Internet and pick up a lot of information.  She also
mentioned the changing of brain chemistry and the excitotoxic effect.  All
in a very short time.  I've been on radio three hours at a time and didn't
answer all questions, there is so much. It is so difficult to get aspartame
on prime time or main stream media, and this was a very large plus, even
though it was short and helped a lot.  Now maybe others will pick it up
from there.

Class Action has not been filed - as of yet.  That's all I can tell you
right this minute.

All my best,  Betty
*************************************************************


http://www.findarticles.com/cf_dls/m0FKA/4_61/54245762/print.jhtml

This story was printed from LookSmart's FindArticles where you can search
and read 3.5 million articles from over 700 publications.
http://www.findarticles.com

http://www.betternutrition.com/

Q&A.
Better Nutrition, April, 1999, by Shari Lieberman

Q From S.K., Johnson City, N.Y.: I am a healthy adult, but suddenly,
experienced a seizure. My brain scan was normal, and there appears to be no
explanation. Is there anything I can take to prevent future seizures?

A There is some evidence that mineral deficiencies may be implicated in
certain types of seizure disorders. Most notably, calcium and magnesium
insufficiencies have been implicated, as well as copper, manganese, and zinc
insufficiencies. Along with a daily multivitamin, I would recommend taking a
comprehensive multimineral supplement that contains all these minerals.
Studies have shown that choline supplementation, as well as dimethyl
glycine, may be beneficial in preventing and treating seizures. Several
studies have shown that taurine may significantly reduce seizures in adults
and children. I would also recommend that you avoid caffeine, alcohol, and
aspartame as these may adversely affect brain chemistry.

Shari Lieberman holds a Ph.D. in clinical nutrition and exercise physiology.
She is a certified nutrition specialist (C.N.S.) and serves on the board of
the American Preventive Medical Association. Write her in care of Better
Nutrition. She cannot answer questions by direct mail or telephone.
Nutrition Hotline is intended for educational purposes only. If you have a
medical problem, consult your physician.
COPYRIGHT 1999 PRIMEDIA Intertec, a PRIMEDIA Company. All Rights Reserved.
in association with The Gale Group and LookSmart.
COPYRIGHT 2000 Gale Group

http://www.betternutrition.com/about.asp
Better Nutrition Mission Statement:
Since 1938, Better Nutrition is in the business of responsibly informing
health-food-store shoppers about the latest breakthroughs in nutritional
approaches to optimal health and ongoing research into vitamins, botanicals
(herbs), minerals and other supplements.
Better Nutrition has always believed that a wholesome, nutritionally dense
diet and a sensible physical-activity program should be at the center of any
attempt to achieve "better nutrition." Research has made it abundantly
clear, however, that customized dietary supplementation with top-quality
products is another crucial component of that approach.
Better Nutrition provides the link between you; the consumer reader
interested in better nutrition, your independent health-food store, and the
products carefully formulated by natural-product companies.
We provide the information, and you determine which diet and lifestyle seem
most promising to you. We don't endorse any supplements. What we endorse is
high-quality research and sensible nutrition.

Consumer Support:
From testifying before committees representing health-food-store shoppers'
rights (New York City Council, February 2000), to lobbying for health-food
shoppers in Washington, D.C. (April 1999), to appearances on radio and
television (FOX-TV "Good Day New York"), Better Nutrition's mission has
always gravitated around the belief that well-informed consumers will have
greater opportunities for optimal health.
Contacting Us:
For editorial questions: editorial@...
For advertising inquiries: advertising@...
For retail store inquiries: retail@...
**************************************************************

http://www.antiageing2004.com/conf/lieberman.php

Cancer, Brain Ageing, Diet & Hormones
Raffles City Convention Centre
June 24th - 27th, 2004, Singapore

Speaker Profiles:
Dr. Shari Lieberman  PhD, CNS, FACN
http://www.drshari.net   drshari@...
Download full CV (23 kb)   [copied at end of post]

Dr. Lieberman earned her Ph.D. in Clinical Nutrition and Exercise Physiology
from The Union Institute, Cincinnati, OH and her M.S. degree in Nutrition,
Food Science and Dietetics from New York University.

She is a Certified Nutrition Specialist (C.N.S.);
a Fellow of the American College of Nutrition (FACN);
a member of the New York Academy of Science;
a member of the American Academy of Anti-Aging Medicine (A4M);
a former officer and present board member of the Certification Board for
Nutrition Specialists;
and President of the American Association for Health Freedom.
She is the recipient of the National Nutritional Foods Association 2003
Clinician of the Year Award and a member of the Nutrition Team for the New
York City Marathon .

Dr. Lieberman's best-selling book The Real Vitamin & Mineral Book is now in
its 3rd Edition (Avery/Penguin Putnam 2003).

She is the author of   Dare To Lose:4 Simple Steps to a Betty Body
(Avery/Penguin Putnam 2002);

Get Off the Menopause Roller Coaster (Avery/Penguin Putnam 2002);

Maitake Mushroom and D-fraction (Woodland Publishing 2001;

Maitake King of Mushrooms (Keats Publishing 1997) and

All About Vitamin C (Avery Publishing Group1999).

Dr. Lieberman is a faculty member of the University of Bridgeport, School of
Human Nutrition graduate program
[ not now listed in their Faculty & Staff Directory
http://www.bridgeport.edu/    University of Bridgeport, 126 Park Avenue,
Bridgeport, CT 06601, 203-576-4552

http://www.bridgeport.edu/pages/39.asp
College of Naturopathic Medicine

The University of Bridgeport College of Naturopathic Medicine is a
non-profit, co-educational professional institution which grants the Doctor
of Naturopathic Medicine (N.D.) degree to graduates who successfully
complete four academic years of study including clinical training. The
program is offered on a full-time basis with no students admitted to a
part-time course of study. There are no correspondence nor distance-learning
courses offered.

Naturopathic medicine is a distinct system of primary health care-an art,
science and practice of preventing, diagnosing and treating conditions of
the human mind and body.

Health Science Center, 60 Lafayette Street, Bridgeport, CT 06606
1-800-EXCEL UB ext. 4108    email: natmed@...

http://www.bridgeport.edu/pages/43.asp

The Nutrition Institute offers an educational and research program
established at the University of Bridgeport since 1977. The goals of the
Institute are to provide a sound understanding of the principles of
nutrition and its valuable role toward attaining a longer and healthier
life. Through our activities in education, internship training programs, and
workshops, we hope to raise the awareness of the value of nutrition in
affecting the wellness of the community.

Registration   Program of Study
The Master of Science curriculum focuses on the role of human nutrition as a
preventative, adjunctive, and alternative strategy for intervention in the
disease process. The curriculum provides a core of basic and advanced
nutrition courses, basic and clinical biochemistry, nutrition education and
counseling, biostatistics, and issues in public health nutrition. Elective
courses are also offered and a thesis or comprehensive exam is required to
fulfill degree requirements.
Accreditation

The Human Nutrition Program is licensed and accredited by the Connecticut
Board of Governors for Higher Education and the Commission on Institutions
of Higher Education, New England Association of Schools and Colleges.
Accreditation by The American Dietetic Association is not required, since
the Master of Science program is NOT a dietetics training program. It does
not include the 900 hours of clinical training required for eligibility to
take the registration examination for the R.D. credential.

Further Information:
Oscar G. Rasmussen, Ph.D.
30 Hazel Street, Bridgeport, CT 06601  Tel: (203) 576-4667
Email: orasmuss@...  ];

an industry consultant;
a contributing editor to the American Medical Associations' 5th Edition of
Drug Evaluations; a peer reviewer for scientific publications;
a published scientific researcher and
a presenter at numerous scientific conferences.
Dr. Lieberman is a frequent guest on television and radio and
her name is often seen in magazines as an authority on nutrition.

Her name appears in Marquis Who's Who of American Women, Who's Who of
Authors and Writers; Who's Who in Medicine and Healthcare, Who's Who of
Emerging Leaders in America and Who's Who Among Young Professionals in the
East, Honored Member Strathmore's Who's Who Millenium Addition 2000-20001.

She has been in private practice as a clinical nutritionist for more than 20
years.

Copyright © Anti-Ageing Conference 2004. All Rights Reserved.Organised by :
Medical Conferences
*************************************************************

http://www.antiageing2004.com/pdf/

Shari Lieberman_long CV_.pdf

Shari Lieberman, PhD, FACN CNS
60 East 8th Street   New York, NY 10003   917-299-8539
http://www.drshari.net  Email: drshari@...

EDUCATION
1982 received M.S. Nutrition, Food Science, Dietetics from New York
University
1993 received Ph.D. Clinical Nutrition, Exercise Physiology from The Union
Institute

MEMBERSHIPS/CREDENTIALS
Certified Nutrition Specialist (CNS) since 1993
Member New York Academy of Science since 1989
Past officer, Certification Board For Nutrition Specialists 1991-1994
Board member Certification Board For Nutrition Specialists 1996-present
Board member American Preventive Medical Association (APMA) 1994-present
President of the American Association for Health Freedom 2003-present
President of the American Association for Health Freedom 2002- present
Fellow of the American College of Nutrition (FACN) since 1999

RELATED ACTIVITIES
Recipient of the National Nutritional Foods Association 2003 Clinician of
the Year Award
Private practice clinical nutrition since 1982 in New York City
Faculty member University of Bridgeport, School of Human Nutrition
graduate program; developed and taught Therapeutic Nutrition course
(1994-1998)
Faculty member New York Chiropractic College (1989-1993)
Author of Dare To Lose (Avery/Penguin Putnam 2002)
Author of Get Off The Menopause Roller Coaster (Avery Penguin/Putnam 2000)
Author of The Real Vitamin and Mineral Book (Avery Publishing Group 1990,
1997 2nd Ed)
Author of Design Your Own Vitamin and Mineral Program (Doubleday 1987)
Member of the Nutrition Team for the New York City Marathon (2003- present)
Nutritional Consultant to:
Garden State Nutritionals (1982-1989)
Windmill Marketing (1982-1989)
Celmark International (Division of Vitaquest International) (1982 - present)
Ginseng Research Institute of America (1982-1990)
Maitake Products, Inc. (1996-1998)
Enzymatic Therapy® (1998-1999)
Europharma (2002 to 2003)
Assisted in the development of a line of nutritional products for and was
on-air talent:
QVC (1997-2003)
Home Shopping Network (1987-97)
Featured authority for numerous books and magazines including with respect
to nutrition:
Rodale Press
Ladies Home Journal
Men's Fitness
Mademoiselle
Contributing editor and columnist for:
Better Nutrition For Todays Living (1983-2001)
Newlife Magazine (1989- present)
Editor of monthly professional newsletter Women's Health Alternative
Medicine (Mary Ann
Liebert, Inc Publishers) 1999-2000
Contributing editor of Complementary & Alternative Therapies a professional
monthly scientific
journal (Mary Ann Liebert Inc. Publishers) 2000- present
Contributing editor for chapter in the 1994 American Medical Association's
Drug
Evaluations entitled, "Treatment of Disorders of Cholesterol and Lipid
Metabolism"
Extensive lecture/presentation experience to professional and lay audiences,
nationally and
internationally
Frequent appearances on TV and radio, quoted in many publications (too
numerous to list)
USA and international product development, technical support, promotion and
sales
Infomercial product development, script writing, technical support, sales
Peer reviewer for scientific journals

OTHER INFORMATION
Listed in Marquis Who's Who:
of American Women
of Emerging Leaders in America
of Authors and Writers
Among Young Professionals in the East
in Medicine and Healthcare
Listed in International Authors and Writers Who's Who

LEISURE ACTIVITIES
Tennis
Aerobic training
Weight training
Travel
Skiing

PROFESSIONAL SCIENTIFIC PRESENTATIONS, ABSTRACTS AND POSTER SESSIONS
January 21, 1991. "Interactive Conflicts: Drug to Drug and Drug to Nutrient
Interventions," Greater Bridgeport Pharmaceutical Association Continuing
Education Meeting, Trumbull, CT.

October 8-1 1, 1993. Poster Session: "Functional Neuromuscular Stimulation:
A
Noninvasive Approach For Objective Evaluation of Muscle Fatigue and Muscle
Recovery Characteristics." Symposium on Advances in Clinical Nutrition,
American College of Nutrition 34th Annual Meeting, Holiday Inn - Mart Plaza,
Chicago, IL.

November 12, 1993. "Vitamin and Mineral Supplementation During Illness."
Wisconsin Dietetic Association 1993 Annual Conference.

December 4-5, 1993. "Not Ill, Not Well - The Viral Crisis." New York
Chiropractic College and Nutrition Education Service continuing education
seminar series. Marriot Hotel, Stamford, CT.

December 18-19, 1993. "Diseases of the Blood." New York Chiropractic College
Center For Postgraduate Continuing Education, Seneca Falls, NY.

June 6, 1994. "Nutritional Supplementation in Clinical Practice."
Philadelphia Dietetic Association.

March 18, 1995. Session 1: "Nutrition and Beauty: Nutrients for Anti-Aging
and
Enhancing Physical Performance and Longevity." Session 2: "Natural Therapy
for Disorders of the Skin - Acne, Psoriasis and Eczema." VIP-Clinique
Medical Conference, Rio Palace Hotel, Rio de Janeiro, Brazil.

April 29, 1995. "Natural, Safe Anti-Virals, Anti-Fungals and Antibiotics for
HIV/AIDS and the Importance of Body Composition For Long-Term Survival." The
First Annual International Congress on Alternative & Complementary Medicine,
Hyatt Regency Crystal City, Arlington, VA.

October 14, 1995. "Effects of Chromium Supplementation on Sugar-Induced
Elevations of Blood Pressure and Lipid Peroxidation in Hypertensive Rats."
Symposium On Advances In Clinical Nutrition, The American College of
Nutrition 36th Annual Meeting,, Omni Shoreham, Washington, D.C.

November 21-22, 1995. "Natural Anti-Virals and Antibiotics in HIV and AIDS,"
"The Importance of Muscle Mass in Maintaining Immune Function," and "A Total
Wellness Program for HIV and AIDS." The First Brazilian-American Symposium
on Orthomolecular and Nutritional Medicine, Copacabana Palace Hotel, Rio de
Janeiro, Brazil.

June 12, 1996. "Natural Anti-Virals For HIV and AIDS," and "Natural
Anti-Inflammatory Agents for Arthritis and Related Disorders." The Second
Annual International Congress on Alternative & Complementary Medicine,
Radisson Plaza Hotel at Mark Center, Alexandria, VA

October 11-13, 1996. Meet the Professor Session - "Wasting Syndromes in HIV
and AIDS," "Comparative Effects of Chromium, Vanadium and Gymnema Sylvestre
on Sugar-Induced BP Elevations in SHR," and "Pro Dietary Supplements."
Symposium on Advances in Clinical Nutrition, The American College of
Nutrition 37th Annual Meeting, Cathedral Hill Hotel, San Francisco, CA

June 21, 1997. "Natural Intervention with Dietary Supplements and Their
Effects On Rheumatoid Arthritis, Osteoarthritis and Related Inflammatory
Disorders," "Niacin As a First Line and Adjuvant Therapy For
Hypercholesterolemia and Related Lipid Disorders." The Second Biomolecular
Medicine Symposium, Brazil-United States, Copacabana Palace Hotel, Rio de
Janiero, Brazil.

September 5-8, 1997. "A Natural Intervention Program For Autoimmune
Disease." Third Annual International Congress On Alternative & Complementary
Therapies, Crystal Gateway Marriot, Arlington, VA.

November 22, 1997. "Exercise, Inflammatory Conditions and Recovery-Nutrition
Views." American College of Sports Medicine 1997 Annual Meeting, Hunter
College, New York, NY.

March 28, 1998. Foundation For Innovative Medicine Symposium. "Conventional
and Complementary Approaches to Breast Cancer" with Robert Atkins, MD,
Michael Schacter, MD, Shari Lieberman, PhD, and Avram Cooperman, MD.

June 21-24, 1998. Chair of Alternative Medicine session. "Natural
Alternatives for Hormone Replacement Therapy for PMS and Menopause." The
Sixth Annual Congress on Women's Health, J.W. Marriot Hotel, Washington,
D.C.

September 16, 1998. Grand Rounds, "Natural Alternatives for Hormone
Replacement Therapy for PMS and Menopausal Symptoms." York Hospital,
Department of Obstetrics and Gynecology, 1001 S George St., York, PA
17405-7198.

October 1, 1998. Panel Chair, "Controversies in Nutrition." Presentation
title, "Natural vs. Pharmacological Treatment For Depression and Anxiety."
American College of Nutrition 39th Annual Meeting, Sheraton Hotel,
Albuquerque, NM.

October 3-4, 1998. Chair, Women's Health section of The Fourth Annual
Congress on Alternative and Complementary Therapies. Presentation title,
"Natural Intervention for Autoimmune Disease." Crystal Gateway Marriot,
Arlington, VA.

December 11-13, 1998. "A Standardized Extract of Grifola Frondosa
(D-Fraction): Immune-Enhancing and Anti-Cancer Effects." American Academy of
Anti-Aging Medicine, 6th International Congress on Anti-Aging and
Bio-Medical Technologies, Early Detection and Reversal of Cancer/Metabolic
Disorders of Aging. Alexis Park Resort and Spa, Las Vegas, NV.

April 10-11, 1999. "Natural Intervention for Autoimmune Disease." Symposium:
Total Immunity for the Next Millennium, sponsored by Allergy Research Group
and Scottsdale Scientific, Inc., Omni Houston Hotel, Houston Texas.

June 12-13, 1999. "Phytohormones In Women's Health: The Prevention of Breast
Cancer and the Treatment of Menopause." American Academy Of Anti-Aging
Medicine: Anti-Aging Therapies for the Office Based Physician, Holiday Inn O
'Hare International, Chicago, IL.

July 12-14, 1999. "Calcium Glucarate: It's Role in Breast Cancer
Prevention." Nutracon '99: The 6th Annual Major Conference and Exhibition on
Nutraceuticals, Dietary Supplements, Functional and Medical Foods. Caesars
Palace, Las Vegas, NV.

March 10-12, 2000. "Anti-Aging Medicine and Cardiovascular Disease
Prevention" and "Phytohormones in Breast Cancer Prevention, Menopause, PMS,
BPH and Prostate Cancer." 1st Congreso Internacional de Medicina Anti-Edad,
Auditorio San Pedro, Monterrey, Mexico, sponsored by La Facultad de Medicina
de la Universidad Autonoma de Nuevo Leon.

March 25, 2000. "Natural Intervention for Hyperlipidemia." Integrative
Medicine: The Bridge to Vitality in the 21st Century: How to Incorporate
Complementary Medicine into Your Practice. Sponsored by Foundation for the
Advancement of Innovative Medicine, New York College, Long Island Jewish
Medical Center, Albert Einstein College of Medicine. New York Marriot,
Brooklyn, NY.

April 18, 2000.. "Effects of Maislin DM (water soluble glucan extract of
Maitake mushroom, Grifola frondosa on glucose metabolism in insulin
resistant KK mice". Poster. V. Monhar, N.A. Talpur, B Echard, S Lieberman ,
HG Preuss, Georgetown University Medical Center. Presented at FASEB Annual
Meeting, San Diego Convention Center.

October 28, 2000. "Natural Intervention for Autoimmune Disease." Workshop.
American College for the Advancement of Medicine, Fall Convention, October
26-29, 2000, Salt Palace Convention Center, Salt Lake City, UT.

November 18, 2000. "Nutraceuticals and the Arthritidies." The 2000 Symposium
on the Geriatric Foot & Ankle, November 18-19, 2000. The Mount Sinai Medical
Center, Annenberg Building, Stern Auditorium, NY, NY. Sponsored by: The
Mount Sinai School of Medicine, The Consortium of New York Geriatric
Education Centers, The New York College of Podiatric
Medicine and The American College of Nutrition.

November 18, 2000. "The Diet Dilemma - One Size Does Not Fit All." 2000
Greater New York Regional Chapter - American College of Sports Medicine
Annual Meeting, November 18, 2000. Hunter College, NY, NY.

September 1-3, 2001. "Nutraceuticals Against Cancer." Cancer Control Annual
Meeting. Sheraton Hotel, Universal City, CA.

December 13, 2001. Chair of Preconference Day: Alternative Cancer Therapies.
"New and Innovative Nutriceuticals in the Battle Against Cancer." 9th
International Congress on Anti-Aging & Biomedical Technologies, Dec 14-16,
2001, The Venetian, Las Vegas, NV.

March 23, 2002. "New and Innovative Nutraceuticals in the Battle Against
Cancer." Latest 21st Century Medical Advances in the Treatment of Cancer and
Aging, March 22-24, The Miami Airport Hilton, Miami, FL.

August 10, 2002. "Alternative Approaches for Psoriasis." National Psoriasis
Foundation 2002 National Conference, August 9-11, 2002, Orlando FL.

May 17, 2002. "Natural Intervention for Hepatitis C." American College for
Advancement in Medicine, New Advances in Complementary Medicine, May 16-19,
2002. Ft. Lauderdale Convention Center, Ft. Lauderdale, FL.

December 7, 2002. "Natural Intervention for Hepatitis C: A Review of the
Scientific Literature." The American Academy of Anti-Aging Medicine 10th
International Congress on Anti-Aging & Biomedical Technologies, December
6-8, 2002, The Venetian Hotel and Reseort, Las Vegas, NV.

August 31, 2003. "Nutrients that Target Cancer." Cancer Control Society 31st
Annual Cancer Convention, August 30-September 1, 2003, Sheraton Universal
City, CA.

October 11, 2003. Moderator: Supplements/Oxidative Stress. American College
of Nutrition Annual Meeting, October 9-11, 2003. Loews Hotel Nashville, TN.

November 16, 2003. Keynote Speaker. 8th Annual Women Healing Women
Conference. Presentations: on Getting Through Menopause Safely and
Naturally, Optimizing Breast Health and The Diet Dilemma. Sheraton Eatontown
Hotel and Conference Center, Eatontown, NJ.

PROFESSIONAL SCIENTIFIC PUBLICATIONS
Lieberman S, Fritz I, Glaser RM, Kuntzman AJ, Shrively R. "Functional
Neuromuscular Stimulation: A Non-Invasive Approach For Objective Evaluation
of Muscle Fatigue and Recovery Characteristics." JACN 1993; 12(5):
610(abstract 107)

Preuss HG, Gondal EB, Bushehri N, Lieberman S. Bryden NA, Polansky NW,
Anderson RA. "Effects of Chromium and Guar on Sugar-Induced Hypertension in
Rats." Nephrol 1995; 44(3): 170-77

Preuss HG, Javed AG, Lieberman S. "Association of Macronutrients and Energy
Intake with Hypertension." JACN 1996; 15(l): 21-35

Preuss HG, Jarrell ST, Scheckenbach R, Lieberman S, Anderson RA.
"Comparative Effects of Chromium, Vanadium, and Gymnema Sylvestre on
Sugar-Induced BP Elevation in SHR." JACN 1996; 15(5): 53l(abstract 65)

Preuss HG, Grojec PL, Lieberman S, Anderson RA. "Effects of Different
Chromium Compounds On Blood Pressure and Lipid Peroxidation In Spontaneously
Hypertensive Rats." Clin Nephrol 1997; 47(5): 325-330

Lieberman S. Nutriceutical Review of St. John's Wort (Hypericum perforatum)
for the Treatment of Depression. J Women's Health 1998; 7(2): 177-182

Preuss HG, Jarrell ST, Scheckenback R, Lieberman S, Anderson RA.
"Comparative Effects of Chromium, Vanadium and Gymnema Sylvestre on
Sugar-Induced Blood Pressure Elevations In SHR." JACN 1998; 17(2): 116-123

Lieberman S. "Treating Depression With St. John's Wort: A Review of Clinical
Trials."Alternative & Complementary Therapies 1998; 4(3): 163-168

Lieberman S. "A Review of the Effectiveness of Cimicifuga racemosa (Black
Cohosh) for the Symptoms of Menopause." J Women's Health 1998; 7(5): 525-529

Lieberman S. "Black Cohosh for Menopausal Symptoms." Alternative &
Complementary Therapies 1998; 4(5): 309-312

Lieberman, S. "Natural Interventions for Treating Autoimmune Diseases:
Current Knowledge and New Possibilites." Alternative & Complementary
Therapies 2001; 7(6): 341-346

Lieberman S, Douwes FR. "Radiofrequency Transurethral Hyperthermia and
Complete Androgen Blockade: A Nonsurgical Approach to Treating Prostate
Cancer." Alternative & Complementary Therapies 2002; 8(3): 149-156

Lieberman S. "Natural Interventions for Hepatitis C: A Review of the
Scientific Literature." Alternative & Complementary Therapies 2002; 8(4):
207-211

Lieberman S. "Natural Interventions for Treating Psoriasis." Alternative &
Complementary Therapies 2002; 8(6): 355-358.

Lieberman S. "Proactive Cancer Prevention and Treatment: An Interview with
Charles B. Simone, M.M.S., M.D. " Alternative & Complementary Therapies
2003; 9(2): 82-85.

Lieberman S. "Statins and ACM: An Integrative Approach to Treating High
Cholesterol: An Interview with Stephen T. Sinatra, M.D., FACC, FACN, CNS.
Alternative & Complementary Therapies 2003; 9(4): 198-201.
**************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.

http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1060 posts in a public searchable archive  119 members

http://groups.yahoo.com/group/aspartame/messages 774 with 16,660 posts
*************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1058
9 of 15 experts reject thimerosal (mercury) in vaccines at US National
Academy of Sciences, Institute of Medicine meeting Feb 9 2004:
qci@...: Murray 3.17.4 rmforall

March 17 2004   Hello Dick Sullivan of QuackBusters@yahoogroups.com ,

I am glad you are planning to write a paper on the aspartame controversy.
As a fellow medical layman, I believe we can serve vital public interests by
offering  civil, independent, unbiased, fully informed reviews.  This
necessarily involves exploring the offerings of biased sources from many
sides in many interrelated controversies.

Surely, it is obvious that the profit motive will inevitably lead some
businesses and governments into collusions that harm public health.

This post shows how one controversy is being exposed, and I add links to
sources about the similarly dubious history of MSG and aspartame.

In mutual service,  Rich Murray  rmforall@...
*************************************************************

http://www.universityofhealth.net/PR/3304PRUSNOMHearing.htm

For Immediate Release
Please freely disseminate with copyright intact

UnInformed Consent
Monday -  March 15, 2004 12:00AM

US National Academy of Sciences
Institute of Medicine
Washington, DC
Immunization Safety Review Committee Hearing
Monday - February 9, 2004 8:30 AM - 5:00 PM

For Online access to this press release go to:
http://www.universityofhealth.net/PR/3304PRUSNOMHearing.htm

Experts Warn Officials -

Massive Mercury Exposure In Vaccines/Amalgam Fillings Linked To Epidemic
Levels of Autism, Neurological Disease.
Allege Conflicts of Interest - Enormous Cover-up.

For Complete In-Depth Coverage and Stats of US National Academy of Sciences
Continuing Investigation..
http://www.universityofhealth.net/NAS/NAS Roster.htm

- UNINFORMED CONSENT, WA DC - Hot accusations of whom to blame swam amongst
rumors that the US National Academy of Sciences nearly canceled their
hearing because of threats.  NAS staff carefully heeled media cameramen and
a daylong pressure cooker of expert testimony began.

The Immunization Safety Review Committee, (ISRC), for the National Institute
of Medicine, (NOM), under the US National Academy of Sciences, (NAS), heard
testimony from 15 experts in a day long "Safety Review" on mercury levels in
vaccines/dental amalgam and links to epidemic levels of autism.
http://www.iom.edu/subpage.asp?id=18065

Whether the CDC, (Centers for Disease Control), (and a fraternity of other
government agencies charged with public safety oversight of pharmaceuticals
and medical practices), have acted in the best interests of pharmaceutical
cartels instead of the public is at the core.

This was the ninth and the latest in a series of hearings that began in
January of 2001 on vaccine safety.  Although in July of 2001, the ISRC
called for the, "removal of thimerosal from vaccines as a precautionary step
in the effort to minimize children's exposure to mercury", no action has
been taken to heed their recommendation.  (See recommendation)
http://books.nap.edu/books/0309076366/html/75.html#pagetop  .

Fears that failure to act may have maimed an entire generation of children
was clearly the primarily focus on the minds of most throughout the hearing.

While opening remarks from the IRSC Chair, Dr. Marie McCormick, defended the
committee's knowledge and commitment by showing the audience a 6 inch binder
of collected data stating the information was "copied on both sides and that
the committee has read them.  Believe me, they have read them."
http://www.streamload.com/UIC/McCormick.rm  (See video of McCormick),

An irascible US Congressman Dave Weldon, (R-FL), also a physician, chastised
the CDC's lack of cooperation.  Weldon stated the CDC have "erected
excessive barriers and have imposed severe limits on access to this data" to
researchers and others in congressional investigations over the past two
years, http://www.streamload.com/UIC/weldon.rm     (See video of Weldon),
http://www.autismcanada.org/News/Weldon.pdf (Text of Weldon address)

The audience consisted of a virtual plethora of powerful interests, included
media, journalists, world acclaimed experts, congressional representatives,
representatives of the FDA, CDC, NIH, ADA, corporate pharmaceutical
executives, a diverse infusion of the dental community and parents of
autistic children, some of them physicians themselves.

1 of 2  Con't

Many of the presentations were of peer-reviewed studies presented by their
own authors.  Each were required to disclose any possible conflicts of
interest in the way of outside funding that might be interpreted as
influencing the outcome of their research and reflect on their credibility.
(See video clips of each expert and disclosures)
http://www.universityofhealth.net/NAS/NAS Roster.htm

Commonly connected were experts who had no conflicts of interest, all
visibly shaken that current practices have exposed an entire generation to a
dangerous level of the powerful neurotoxin mercury without consideration of
the bio accumulative consequences.  Some even chastised themselves for their
own failure to act sooner when waves of parents of autistic children begged
them to listen.  (See video clips of each expert and disclosures)
http://www.universityofhealth.net/NAS/NAS Roster.htm

One expert, Dr. Marc Geier, a physician, board certified geneticist and
vaccine researcher, has been doing research for over 30 years.  Geier has
published in over 30 different peer-reviewed publications has been
investigating vaccine safety, including the CDC's own Vaccine Adverse
Effects Reporting System, (VAERS), for Congress.    Geier told the
committee,  "This society is going to be in big trouble - we cannot have a
whole generation of people damaged the way this is happening."   Geier went
on to say vaccine manufacturers have begun to mislabel vaccines so that the
thimerosal cannot be tracked.  "I must say I'm a little bit embarrassed to
stand here and listen to Verstraeten's work being presented after what they
said at Simpsonwood,"  (referring to an ad hoc meeting at the Simpsonwood
Meeting Center in Atlanta in 2000 discussing what to do about Verstraeten's
original and alarming findings). " This is NOT a scientific issue.  This is
about as proven issue as we're ever going to see.  What's occurring here is
a cover-up under the guise of protecting the vaccine program."

After discussing various studies and presenting some compelling studies of
his own, Dr. Boyd Haley, PhD, Chemistry Chair at the University of Kentucky
stated he was "baffled how there can be such different results from people
using the same database," To which one IRS committee member retorted,  "Are
you implying the epidemiologists lied?"  Haley responded,  "I'm implying
that some epidemiologists lied, yes."

Only four of six of those with succinct conflicts of interest with funding
from pharmaceutical interests could represent that they found no problem
with the powerful additive, mercury.  The remaining two had unclear but
likely conflicts of interests and rescinded an opinion. (See video clips and
stats of experts and disclosures)  http://www.universityofhealth.net/NAS/NAS
Roster.htm

Media and for more in depth information on this developing story contact:
UnInformed Consent - 425 487 2358 - qci@...  or visit:
www.uninformedconsent.com

Copyright © 2003 QCI. All rights reserved. Republication and redissemination
of these contents are expressly prohibited without QCI prior written
consent.
2 of 2 -  End
*************************************************************

http://www.universityofhealth.net/NAS/NAS%20Roster.htm

US National Academy of Sciences
Institute of Medicine
Washington, DC
Immunization Safety Review Committee Hearing
Monday - February 9, 2004 8:30 AM - 5:00 PM

Out of 15 speakers polled:

60% (9) felt there IS a link to Autism etc.  (This represents all those with
NO conflicts of interest)

26% (4) felt there is NO link to Autism etc. (This represents all those WITH
conflicts of interest)

14% (2) were noncommittal.   (This group likely to have conflicts of
interest)

100% of those with no conflicts of interest are convinced there is a massive
problem.

(See Stats on Consensus)

In Order of Appearance..

Marie McCormick, MD, Committee Chair, introduced Congressman Dave Weldon,
(R-FL).  In addition to an explanation of the committee's duties, she
defended the committee's knowledge base by showing the audience a 6-inch
binder of collected data and stating information was copied on "both sides
and the committee has read them.Believe me they have read them." (See Video)

Congressman Dave Weldon, (R-FL), (also a physician) indignantly delivered a
scathing address riddled with a long list of how the CDC, along with other
agencies like them, have been less than forthcoming - citing instance after
instance of the CDC's  "appearance of conflicts of interest". (See Video)

Dr Mary Hornig, MD, Associate Professor, Columbia University shared a study
on mice who were introduced to the same ratio of mercury, per body size that
humans are exposed to.  "The exposed mice had abnormal behaviors compared to
the control group including aggressive tail biting, self mutilating, wildly
self-grooming, frantically grooming his partner eventually grooming through
his partner's skull, thus killing his own partner."

Possible Conflicts of Interest  - Although she has had funding from a
variety of pharmaceutical manufacturers who produce vaccines and the NIH,
she has no specific funding for looking at safety in vaccines.  She has also
received funding from Safe Minds.

Opinion on Safety - Dr. Hornig has serious concerns with accumulative
mercury exposure through the use of thimerosal, mercury in vaccines, and
other applications in the many other products in which it is contained.
(See video)

Dr. Kumanan Wilson MD MSc, of the Toronto General Research Institute,
Canada, reviewed over multitudes of case studies, some with significant
association between thimerosal and autism and some inconclusive.

Possible Conflicts of Interest - Dr Wilson could not and did not verify any
conflict of interests of his own or within the many studies he reviewed.
Opinion on Safety - Dr. Wilson did not reach any definitive conclusions.
(See video)

Dr. Frank DeStefano, MD, Centers for Disease Control and Prevention and one
of the co-authors along with another scheduled speaker, Dr. Robert Davis, of
the infamous and controversial Verstraeten study, presented another study he
co-authored initially for mental retardation, Cerebral Palsy, hearing loss
and visual impairment.  Autism Spectrum Disorder was added in 1996.

Possible Conflicts of Interest  - The Verstraeten study in February 2000
found a definitive and causal connection between thimerosal and autism,
speech delays and ticks with 110,000 children from two HMOs.  Dr.
Verstraeten presented at a hearing in this committee in 2001.

At a secret review hearing held at the Simpsonwood Meeting Center in
Atlanta, Georgia in June of 2000, 50 some experts, all personnel from the
CDC, NIH, FDA and affiliated groups, spent the weekend reviewing the
alarming data.  This information was embargoed from the public.

In November of 2003, three years later, a watered down version of the same
study, this time claiming no connection between thimerosal and autism,
appeared in peer - reviewed publication, Pediatrics, where it was
immediately attacked by peers for manipulation.   It sparked a series of
claims of fraud and an investigation into the CDC from members of Congress
that not only remains unresolved but also is escalating at an explosive
rate.

The study's main author, Thomas Verstraeten, has been working for
GlaxoSmithKline since July of 2000 and is unavailable in Belgium.  The
information that Verstraeten and his co authors worked for pharmaceutical
manufacturers was apparently not disclosed to the publishers of Pediatrics
when the new revised version of the study was submitted. (See Peer Reviews
in Pediatrics) -

DeStefano claims at this hearing none of his co-authors have conflict of
interests on the study he presented-- however, his states the CDC provided
all the support for the study he presented.

Critics claim the CDC is collaborating with vaccine manufacturers when they
are supposed to act in an oversight position.

Opinion on Safety - DeStefano seemed to mix categories of his study groups,
cohorts, to the degree that many in the audience, including committee
members, appeared confused as to what his position really is.  (See video)

Dr Elizabeth Miller, Head Immunization Division, Public Health Laboratory
Service, Communicable Disease Surveillance Centre, London, UK, well known in
research circles and the UK alike for her abrasive style and lead in the
concerted and unprovoked attack on Dr. Andrew Wakefield who expressed his
concerns on the possible autism link to thimerosal on the UK television
program Panorama several years ago.  (See Panorama)

Wakefield has been an undaunted thorn in the side of the UK government
authorities since he went public in 1998 with his concerns in that vaccines
may be related to autism.  These aggressive attacks by Miller and others
affiliated with funding from pharma, were the subject of Congressman Weldon'
s welcome address at this NOM hearing.  Dr. Wakefield's research was one of
the first alarms that riveted through the medical community and has been
largely validated by many other researchers.

Possible Conflicts of Interest  - Her disclosures do not appear to be
totally forthright of her close ties with vaccine manufacturers.  (See More
Elizabeth Miller)

The serendipitous appearances of experts in the field who response to
questions of safety with anger and misdirection instead of facts that
appear, by design, to mislead the medical community and the public has been
the subject of an explosion of "conflicts of interest" allegations.

Public reaction to these open attacks appears to be one of cynical sentiment
and a growing movement by the US and the UK populations alike to question
the credibility of their own governmental agencies.   The use of
"alternative" medicine in both the UK and the US is on a rapid rise leaving
the pharmaceutical market share dwindling.

Pharma's aggressive response to this situation has been the subject of much
press in their attempts to gain control of the supplement industry through
quiet purchasing of preferred brands and pressuring for FDA and CDC control
of the supplement and alternative industry through congressional bills to
change these agencies's authority.

Critics claim pharma's fight to control the sales of pharmaceuticals outside
the US is only a symptom of a desperate pharma to reclaim a disenchanted
market share.  This has created much furor in congressional circles and the
senate alike as pharma flexes its well-financed lobbying mercenaries against
a growing and passionate grassroots movement to protect the public who
threaten campaigns to recall those who throw a deaf ear to public safety.

Opinion on Safety - Despite many other experts claims to the contrary, Dr.
Miller feels there is no evidence that increasing exposure to thimerosal at
a young age increases the risk of autism.

During much or the day, a hostile Miller spent an unusual amount of time
defending her position that thimerosal was safe during the Q&A of experts
who did not subscribe to her position.  In some cases she contradicted
herself.  Critics question what is rational about getting hostile over a
concern of safety and thus question her credibility.   (See video)

Dr. Robert Davis, MD MPH University of Washington, Group Health, Cooperative
Dept. of Pediatrics, Center for Health Studies and Epidemiology, and one of
the co-authors along with another scheduled speaker, Dr. Frank DeStefano, of
the infamous and controversial Verstraeten study, presented and reviewed
some of the Verstraeten study at this hearing.  Dr. Verstraeten presented at
a hearing in this committee in 2001.

Possible Conflicts of Interest  - The Verstraeten study in February 2000
found a definitive and causal connection between thimerosal and autism,
speech delays and ticks with 110,000 children from two HMOs.

At a secret review hearing held at the Simpsonwood Meeting Center in
Atlanta, Georgia in June of 2000, 50 some experts, all personnel from the
CDC, NIH, FDA and affiliated groups, spent the weekend reviewing the
alarming data.  This information was embargoed from the public.

In November of 2003, three years later, a watered down version of the same
study, this time claiming no connection between thimerosal and autism,
appeared in peer - reviewed publication, Pediatrics, where it was
immediately attacked by peers for manipulation.   It sparked a series of
claims of fraud and an investigation into the CDC from members of Congress
that not only remains unresolved but also is escalating at an explosive
rate.

The study's main author, Thomas Verstraeten, has been working for
GlaxoSmithKline since July of 2000 and has been unavailable in Belgium.  The
information that Verstraeten and his co authors worked for pharmaceutical
manufactures was apparently not disclosed to the publishers of Pediatrics
when the new revised version of the study was submitted. (See Peer Reviews
on Pediatrics)

At this hearing, Davis reveals numerous and deeply disturbing conflicts of
interest at this meeting but apparently not all of them.  An investigation
reveals $5 -$7 million in pharm funding alone.  Critics allege he has not
disclosed his financial involvement with the financial melting pot -
Brighton Collaboration that appears to be a money-laundering vehicle for a
who's who of government agencies such as the FDA, NIH, CDC and
pharmaceutical companies collecting additional income under the claim of
tracking vaccination adverse effects.

Davis's own curriculum vitae on the Internet states six plus million from
pharmaceuticals cartels.  (See Davis on line CV disclosures).  (See Funding)

Opinion on Safety - Although Davis states autism is primarily diagnosed at
around 10 months, (44+ weeks), he then concludes there is no evidence of
dose response at three different ages, 1 month, 3 months and 7 months, ages
where autism is rarely diagnosed.  Critics allege this is deliberately
misleading.

During his presentation at this hearing, when reviewing the IOM recommended
in 2001, he appears to have left out the specific recommendation that called
"for the removal of thimerosal from vaccines as a precautionary step in the
effort to minimize children's exposure to mercury."   (See 2001 NOM
Committee recommendations)    (See video)

Anders Peter Hviid, MSc, Department of Epidemiology Research, State Serum,
Institute, Copenhagen, Denmark presented a study of the association of
Thimerosal-containing vaccine and autism in Denmark or the "Denmark study"
mentioned by several others during the day.

Possible Conflicts of Interest  - During his disclosures of possible
conflicts of interest, he did not mention the work he has done for private
vaccine manufacturers who supply the vaccine for his government agency that
he also works for.

Opinion on Safety - Hviid states his study shows no relationship between
Thimerosal and autism.  Questions from the audience shed doubt on how the
study was calculated going as far as one comment that it, (the study), was
like "comparing apples to cows."  This reflected on Hviid's credibility as a
whole.  (See Video)

Dr. Mark R Geier MD PhD, President, The Genetic Centers of America and David
Geier, President of MedCon are part of the research team commissioned by
Congress to review the CDC's Vaccine Adverse Effects Research database.

Geiers are also part of the congressional authority who were denied access
for the most of part of the past two-years by the CDC to this database.
Rep. Weldon referred to this in his opening statements.

Possible Conflicts of Interest -They have been summoned and reported to
Congress as expert witnesses many times and have been called as expert
witnesses in other actions.  They disclosed no conflicts of interest.

Opinion on Safety - Given that their presentation consisted of countless
studies showing alarming findings of massive exposures.  The IOM choose not
give them any extra time to review the data for the committee as they did in
for another presenter earlier.  As a result they were not able to go into
depth on any of them.  There was no doubt about their position that if this
exposure is not addressed immediately  "that this society is going to be in
big trouble - we cannot have a whole generation of people damaged the way
this is happening."   (See video)

Breaking News:  Immediately after Geier's presentation at the NOM, in a
letter dated February 13, 2004, the acting Assoc. Dir. For Science at the
CDC, Jeanne Santoli, MD, shut down their access to extract data from the CDC
database stating "potential breaches in confidentiality."   This set off a
chain reaction of outrage through the Congressmen who commissioned the
research and others than has yet reached critical mass.
(See CDC/Geier letters)

Dr. H. Vasken Aposhian, PhD, Professor, Molecular and Cellular Biology,
University of Arizona presented a toxicologist's view of Thimerosal and
autism.  Dr. Aposhian reviewed over science available and the US standards
of what is considered safe and determined that there is a definitive causal
connection between over accumulative thimerosal and autism.

Possible Conflicts of Interest - Dr. Aposhian disclosed no conflicts of
interest.

Opinion on Safety - "It is this toxicologist's view that the link between
thimerosal and neuro development disorders in children has become more
plausible. Thimerosal appears to add organic mercury to the mercury burden
of the mercury of children with mercury efflux disorder."   (See video)

Dr. David Baskin, MD Professor of Neurosurgery and Anesthesiology, Baylor
College of Medicine did a presentation of neurotoxic effects of thimerosal
to autism.

Possible Conflicts of Interest - Dr. Baskin disclosed funding in
relationship to his studies in his field and appeared to be related to
research unrelated to vaccine manufacturers.

Opinion on Safety - Baskin clearly feels there is an issue referring to
replicated studies at MIT "is at least alarming and is of concern."  (See
video)

Dr. Polly Sager, Assistant Director for International Research, National
Institute of Allergy and Infectious Diseases under the National Institutes
of Health, presented evaluations of mercury in infants after thimerosal
containing vaccines and examines several possibilities.  She reminded the
audience that their studies were done on the maternal hair not from maternal
blood levels using the studies on damaged children in Iraq as an example.
She reviewed over a study that looked at safety standards thimerosal
exposure form vaccines and ethyl mercury accumulation in non-human primates.
She states the study itself is fairly incomplete and not as useful for this
hearing as it might be in the future.

Possible Conflicts of Interest - Sager disclosed some of her previous
funding and believes she has no conflicts of interest.  Sager's primary
employer is the National Institute of Allergy and Infectious Diseases under
the NIH.

The NIH has been the subject of numerous and recent US Senate hearings
alleging conflicts of interest within the National Institutes of Health and
large pharma.

Some critics allege that any insinuation that a reaction to mercury as an
allergy is misleading and the legitimacy of granting funding through the NIH
and the National Institute of Allergy and Infectious Diseases is thus
inappropriate.

The National Institutes of Health, (where the National Institute of Allergy
and Infectious Diseases resides), have been the subject of some critical
scrutiny due to their open policies on personnel accepting outside sources
of funding including pharmaceutical interests. Coverage on recent US Senate
investigating these allegations by the LA Times -  (See LA Times)  (See
additional LA Times Story)
http://pqasb.pqarchiver.com/latimes/483567461.html?MAC=cfb1287b70ba5bfebbabb7536\
276bd7f&did=483567461&FMT=FT&FMTS=FT&PMID=&printformat=&desc=Stealth+Mer
ger:+Drug+Companies+and+Government+Medical+Research%3b+Some+of+the+National+
Institutes+of+Health%27s+top+scientists+are+also+collecting+paychecks+and+st
ock+options+from+biomedical+firms.+Increasingly,+such+deals+are+kept+secret

Opinion on Safety - This presentation reviewed over where mercury was found
in the brain and blood of primates and no conclusion was addressed as to
safety issues because of the incomplete status of the study. (See video)

Dr. Boyd Haley PhD, Chairman and Professor, Department of Chemistry,
University of Kentucky is one of the premiere world experts on mercury
exposure. Haley presented numerous studies.  One study was done on mercury
in the birth hair of children and the relationship between the amount of
amalgam fillings in the mother and the birth hair where the mercury burden
of the fetus could be correlated to the amount of dental amalgam fillings in
the mother.Another study was done on the effects of testosterone combined
with mercury on brain neurons and the effects of estrogen combined with
mercury on brain neurons where it was found that testosterone exacerbated
the toxic affects of mercury on the brain neurons and estrogen seemed to
protect the brain neurons.

Haley discussed the role of mercury in other medications including
Idiopathic Dilated Cardiomyopathy, (IDCM), where young athletes die suddenly
and have been found with massive amounts of mercury in their heart tissue.
Haley states it is a "very distinct possibility" these young people are
injecting Thimerosal containing testosterone instead of steroids in an
attempt to enhance performance.

Possible Conflicts of Interest - Haley disclosed some funding from private
sources.  Haley has received no funding from pharmaceutical interests.

Opinion on Safety - Haley believes there is an alarming amount of exposure
of an accumulative amount of mercury in the population from amalgam and
vaccines as well as environmental.

Referring to Haley's statement that he is "baffled" how there can be "such
different results from people using the same database," one committee member
asked, "Are you implying the epidemiologists lied?"  Haley responded,  "I'm
implying that some epidemiologists lied, yes."

  "There appears to be a subset of the population that cannot effectively
excrete mercury and are at greater risk to exposures to mercury than are the
general population.  Genetic susceptibility is critical.  Presence of other
heavy metals enhances susceptibility.Estrogen decreases thimerosal toxicity
where testosterone enhances toxicity.  Gender effects are involved." (See
video)

Dr Jeff Bradstreet, MD FAAFP, Adjunct Professor, Neurosciences, Stetson
University, Director of Clinical Programs, International Child Development
Resource Center, Florida.

Possible Conflicts of Interest - Disclosed sponsors CRC Stetson University.
Bradstreet asked the committee to give an opportunity to have the Wakefield
and Dr. Oleary team present their information and believes it critical to
their information.

Opinion on Safety - "Is very concerned about mercury in general.and I'm even
more concern after 600,000 children were added to the at risk group of
mercury from dietary exposure from fish eating. Exposing children to a
neurotoxin, even at a theoretical level is an unwise practice."   (See
video)

Dr. Vijendra K Singh, PhD, Research Associate Professor, Utah State
University presented autism, vaccines, and immune reactions.  His studies
show consistent finding of measles virus in autism children.

Possible Conflicts of Interest - Singh states he has no conflict of interest
from anyone.

Opinion on Safety - Singh believes his studies show that the measles virus
is a serious player in the neurological epidemic seen in autistic children.
He thinks it is time to re-evaluate vaccine safety and the manner in way we
practice vaccines today.  (See video)

Highlights and Interesting Remarks -

Dr. Elizabeth Miller seems to say to Dr. Haley that the UK vaccination
schedule has the same exposure as the US with no incidence of autism.
Earlier she states the UK does not vaccinate for Hepatitis B and flu, (like
the US), and there is no incidence of autism.(See video)

Geier interview with CNN. (See video)

Stats:

Is there a link to Autism etc and vaccines?Conflicts of Interest?

Weldon     YES   NONE
Hornig       YES   NONE
Wilson       Could not say   Not definitive
Destefano  NO    YES
Miller         NO    YES
Davis         NO    YES
Hviid          NO    YES
Geier          YES   NONE
Geier          YES   NONE
Aposhian    YES   NONE
Baskin        YES   NONE
Sager          Possibly   Possibly
Haley          YES   NONE
Bradstreet   YES   NONE
Singh           YES   NONE

Media and for more in depth information on this developing story contact:
UnInformed Consent - 425 487 2358 or visit:
www.uninformedconsent.com

E-mail UnInformed Consent:  qci@...

Copyright © 2003 QCI. All rights reserved. Republication and redissemination
of the contents of this screen are expressly prohibited without QCI prior
written consent.

http://www.universityofhealth.net/UICPressReleases.html

http://www.universityofhealth.net/UofHhome.html

http://www.universityofhealth.net/InterestingLinks.html

http://www.universityofhealth.net/index.html
**************************************************************

http://groups.yahoo.com/group/aspartameNM/message/629
Rich Murray: Haley: brilliant testimony to Congress on health fraud
re dental amalgam mercury and Alzheimers  Part 1/2  6.12.1 rmforall
Part 1/2  http://www.mercola.com/2001/jun/9/amalgam_safety.htm

http://groups.yahoo.com/group/aspartameNM/message/630
Rich Murray: Haley: brilliant testimony to Congress on health fraud
re dental amalgam mercury and Alzheimers Part 2/2 6.12.1
Part 2/ 2  http://www.mercola.com/2001/jun/9/amalgam_safety2.htm

Boyd E. Haley Professor and Chair behaley@...
Department of Chemistry University of Kentucky
http://www.uky.edu/

http://www.truthinlabeling.org/    Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD   The toxicity/safety of processed
free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999;  6:  259-310.  52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333   adandjack@...

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research 7.31.2 rmforall

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 7.10.0 rmforall

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9: rmforall

http://groups.yahoo.com/group/aspartameNM/message/927
Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2 rmforall
*************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.

http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1058 posts in a public searchable archive  119 members

http://groups.yahoo.com/group/aspartame/messages 770 with 16,594 posts
*************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1057
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

We may combine two new general theories of the role of the universal
neurotransmitter glutamate and its activity with the N-methyl-D-aspartic
acid (NMDA) glutamate receptors in neurons in all parts of the brain.

A unified vision is then available for the full spectrum of puzzling
neurological disorders, ranging from overactivity of brain glutamatergic
neurotransmission in the closely related disorders Multiple Chemical
Sensitivity, Chronic Fatigue, Post Traumatic Stress Disorder, and
Fibromyalgia, often triggered by carbon monoxide or formaldehyde (and thus
methanol and aspartame), as outlined by Pall, to the opposite pole of
deficient glutamate activity in schizophrenia, described by Coyle, Goff,
and Javitts.

My goal here is to outline the broad vision and highlight some intriguing
specifics, not offer complete analyses, reviews, or proofs, and make
available access to the two major sources.   Coyle described similar
connections in 1993:

[ Science. 1993 Oct 29;  262(5134):  689-95.
Oxidative stress, glutamate, and neurodegenerative disorders.
Coyle JT, Puttfarcken P.
Department of Psychiatry, Harvard Medical School, Belmont, MA 02178.

There is an increasing amount of experimental evidence that oxidative stress
is a causal, or at least an ancillary, factor in the neuropathology of
several adult neurodegenerative disorders, as well as in stroke, trauma, and
seizures.
At the same time, excessive or persistent activation of glutamate-gated ion
channels may cause neuronal degeneration in these same conditions.
Glutamate and related acidic amino acids are thought to be the major
excitatory neurotransmitters in brain and may be utilized by 40 percent of
the synapses.
Thus, two broad mechanisms--oxidative stress and excessive activation of
glutamate receptors--are converging and represent sequential as well as
interacting processes that provide a final common pathway for cell
vulnerability in the brain.
The broad distribution in brain of the processes regulating oxidative stress
and mediating glutamatergic neurotransmission may explain the wide range of
disorders in which both have been implicated.
Yet differential expression of components of the processes in particular
neuronal systems may account for selective neurodegeneration in certain
disorders.
Publication Types: Review   Review, Academic   PMID: 7901908 ]

The vision of the full spectrum immediately makes available productive
research and treatment strategies.   Genetic and environmental factors could
shift a person toward either pole.  When the shift is too extreme in either
direction, we have disorders ranging from MCS to schizophrenia.  What causes
one pole (high activity) may treat the opposite pole (low activity), and
vice versa.

What positive selection values would there be for severe MCS, about 4% of
the USA population?  What could be the subtle advantage that would maintain
complex gene patterns for high glutamate activity for the last million years
of human evolution?   Likewise, why does 1% of humanity have schizophrenia,
a devastating and often fatal, usually lifelong disorder, characterized by
low glutamate activity?

The taming of fire with hearths and lamps in caves, huts, tents, and then
ships was of supreme selection value.  Complex genetic systems would have
evolved for attraction to fire and smoke.  However, carbon monoxide exposure
binds up hemoglobin and so produces chronic oxygen deficits.  The brain
needs a lot of oxygen.  Inherently high levels of glutamate activity on the
NMDA receptors would enable the brain to compensate.  We see how it is that
many writers and executives, with their intense, unremitting mental effort,
often used to  smoke all day, even though the brain is extremely dependent
on oxygen.

Humanity, enjoying fire,while enduring lifelong exposure to carbon monoxide,
had to suffer  high NMDA glutamate activity, with its multitude of damaging
disorders.  Evolution would then  select for complex patterns of genes that
favor compensating genetic dispositions with tendencies towards low
glutamate activity, increased schizophrenia, and reduced MCS. Then, lifelong
exposure to carbon monoxide would stimulate the lower glutamate activity and
poorer brain functioning back into a normal range.

Perhaps, given the much shorter lifetimes in Stone Age societies, the
predilection for schizophrenia would not have had a chance to activate often
in an average lifespan of about twenty.  So, with an increasing lifespan
from the Neolithic on,  low glutamate activity and schizophrenia may have
become more common.  Much later, the warming climate may have caused less
lifelong exposure to warming fires and carbon monoxide from smoke, also
leading to less activation of glutamate NMDA activity and thus more
schizophrenia.

So, selection would operate in both directions on the spectrum of glutamate
activity, fostering the evolution of humans who have complex genetic
capabilities for both poles.  As we know, about  4% have severe MCS, while
about 1% have schizophrenia.  The complex trade-off balance between the two
patterns must involve a multitude of factors: race, sex, age, diet, social
role, climate, toxic exposures, and fundamental cultural attitudes, such as
aggressiveness versus passivity.

A few confirming facts are available in "Surviving Schzophrenia: A Family
Manual", 1988, E. Fuller Torrey, M.D.  Schizophrenia prevalence, which since
1945 ranges worldwide from less than 1  to 17 per 1000, commonly 2 to 5 per
1000, is lowest  in Ghana, Papua New Guinea, and Taiwan, and highest in
Scandinavia and western Ireland.

About 60% of schizophrenics smoke tobacco, dosing themselves with nicotine,
which activates NMDA receptors, thus tending to treat their disorder.  The
simultaneous exposure to carbon monoxide in tobacco smoke may help by
triggering various reactions that also increase NMDA  glutamate receptor
activity.  Schizophrenics also have very high levels of alcoholism.

Humans started growing grains about 10,000 BP, and milk fat has been found
in 6500 BP pottery in Britain.   It is now well known that both grain
cultivation and cow domestication originated in the warm Middle East, and
spread west for thousands of years by slow population movement into colder
areas, along with languages and cultural patterns.  Genetic patterns for
normal NMDA receptor activity would have partially mixed with the indiginous
genetic patterns for  low activity in the cold regions.  Scandinavia and
western Ireland, which have very high schizophrenia incidence, also have
very low lactose tolerance, and a high level of celiac disease, caused by a
genetic inability to tolerate gluten from grains.  William W. Eaton, PHD
recently reported that in Denmark the risk of schizophrenia was three times
higher for those with a history of celiac disease, but not Crohn's disease
or ulcerative colitis.
http://www.sciencedaily.com/releases/2004/02/040220081037.htm  Feb. 20, 2004

It helps and it hurts.  This bipolar aspect also shows up in the use of
ethyl alcohol drinks, which always have a methanol impurity, especially in
crude Neolithic drinks, which the liver converts to formaldehyde, producing
hangover symptoms after many hours, and also triggering high glutamate
activity.  Ethyl alcohol, by causing red blood cells to clump, reduces
oxygen transport, slowing the cortex, producing dullness and relaxation.
The formaldehyde stimulates.  So there are complex cycles of  disinhibition,
relaxation and rest, alternating with excitment and stimulation-- the stuff
of Homeric epics.

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

In the same way, I conjecture that schizophrenics or those with too low
glutamate activity may use aspartame, since its 11% methanol component is
immediately released in the GI tract and within hours largely turned by the
liver into formaldehyde, which is a main trigger for NMDA glutamate
activity.  This would be an example of hormesis, the paradoxical phenomena
of beneficial effects from low doses of toxins.

http://groups.yahoo.com/group/aspartameNM/message/1056
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 3.11.4

In upshot, humans have evolved to use diet, smoke, herbs, and chemicals to
manipulate their brain activity along a spectrum of glutamate NMDA activity.
We can try to appreciate the complex possibilities available between the two
poles.

[ For an earlier speculation:
http://groups.yahoo.com/group/aspartameNM/message/764
Wheeler: Ewald: positive selection for neurotoxins (aspartame)?
Murray 11.25.1 rmforall ]

This includes the inborn tendency to seek out and try strange-tasting
substances that shift energy and awareness, and, if they are not acutely
fatal,  become addicted to them and use them for social bonding, as in
"sharing a congenial drink" , "smoking the peace pipe", "passing a joint"---
sugar, grains, alcohol, milk foods, caffeine, tobacco, chocolate, chili,
pepper, nutmeg, marihuana, heroin, cocaine, ecstacy, aspartame, the panoply
of food additives, dyes, sweeteners, and drugs-- an rapidly evolving chaos
of uppers and downers, woven into the fabric of modern daily life.

We see current national leaders, Bush, Clinton, Gore, Clark, John Edwards,
Howard Dean,  and Dean's former campaign manager, Joe Trippi, consuming up
to 3 liters diet soda daily, while functioning capably.  Perhaps the
formaldehyde-induced glutamate actvity stimulation, along with the high
levels of caffeine,  faciliates dealing with stress, fatigue, sleep
deprivation and the debilitating effects of the modern urban diet--
particularly on the campaign trail.
*****************************************************************

http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

Dec 9 2002  [ Notes by Rich Murray are in square brackets. Pall has 45
items in PubMed since 1969.

The theory is quite complex.  Most readers will not be familiar with the
biochemistry. I will focus on the many diseases that may be involved, more
and less,  on MSG and on formaldehyde (an inevitable product of methanol,
the 11% component of aspartame), and the prospect for new diagnostic tests
and for treatments for aspartame disease.

Pall's article is available on the Web at
http://www.fasebj.org/cgi/content-nw/full/16/11/1407/T1.
Access to this site is free to members of the Federation of American
Societies of Experimental Biology.  Others must pay a $7 access fee. ]

http://www.wsunews.wsu.edu/detail.asp?StoryID=3281
News Bureau  Washington State University  wsunews@...

Pullman, WA 99164-1040   509/335-3581  FAX: 509/335-2220
See a complete list of news releases on the Web at: http://wsunews.wsu.edu
Online Experts Directory: http://experts.wsu.edu

9/16/2002
Contact: Sharon Hatch, 509/335-4262, hatch@...
Martin  L. Pall, 509/335-1246, martin_pall@...

WSU Biochemist Suggests Vicious Chemical Cycle May Cause
Multiple Chemical Sensitivity

PULLMAN, Wash. -- In the United States about 10 million people are afflicted
by severe multiple chemical sensitivity. Many MCS sufferers give up air
travel, some must find new work places or move out of their homes to avoid
exposure to certain chemicals. For them, grocery shopping in the detergent
aisle or attending events where someone may wear perfume is risky. MCS
symptoms, which may last for hours or days, include pain (severe headaches
and pain in joints and muscles), fatigue, dizziness and an impaired ability
to think clearly.

The onset of this chronic condition can usually be traced back to an
exposure to certain chemicals. But why the initial exposure results in an
often life-long, incurable condition has been a mystery. In an article
published in the September 2002 issue of the prestigious publication of the
Federation of American Societies of Experimental
Biology, "The FASEB Journal," Washington State University biochemist Martin
Pall suggests that a vicious chemical cycle may be to blame.

Pall's new theory is a fusion of two previous theories about MCS. One of
these, proposed by Pall earlier, states that MCS is produced by excessive
levels of two chemicals in the body-nitric oxide and its oxidant product -
peroxynitrite. He suggested certain mechanisms act to keep levels of the two
compounds elevated, thus producing chronic changes. The second theory was
proposed by Iris Bell, M.D, Ph.D. of the University of Arizona. She proposed
that the central mechanism in MCS is neural sensitization in the brain.

"What my article reports," said Pall, "is that if you assume both previous
theories are correct, you come up with a fusion that explains all the most
puzzling features of MCS. It explains why MCS is induced by a previous
chemical exposure and why MCS sufferers show such a high level of
sensitivity to a wide range of organic chemicals."

Pall cites many studies that suggest that the initial chemical exposure
creates a hypersensitivity in the neurons in the brain, which react by
creating the two chemicals that cause further hypersensitivity.
"Ordinarily, these activities are highly regulated, acting only on specific
synapses in the brain where they are involved in learning and memory. The
MCS response is produced," said Pall, "when chemical exposure produces
excessive responses over large regions of the brain. In this way, normal and
important mechanisms may act to generate this chronic illness. Thus, not
only is the brain constantly inundated by chemicals to which it is normally
somewhat sensitive, but the brain of a person suffering from MCS becomes
abnormally sensitive to the chemicals-- from 100 to 1,000 times more
sensitive than in an unaffected person." Two other mechanisms contribute to
the sensitivity to by allowing the offending chemicals to accumulate to
higher levels in the brains of MCS people.

MCS has overlaps with other medical conditions of uncertain mechanism
including chronic fatigue syndrome, fibromyalgia, posttraumatic stress
disorder, and Gulf War syndrome. Pall has proposed similar mechanisms for
all of these conditions. "The notion that a biochemical vicious cycle may
underlie all four is very exciting and, if correct, suggests that this is a
major new paradigm of human disease."

Interrupting this cycle may be the key to effective MCS treatment, said
Pall.

Pall's article is available on the Web at
http://www.fasebj.org/cgi/content-nw/full/16/11/1407/T1.
Access to this site is free to members of the Federation of American
Societies of Experimental Biology. Others must pay a $7 access fee.

Comments:  Dr. Gunnar Heuser, neurotoxicologist and clinical professor at
UCLA, who has published on brain changes in Chronic Fatigue Syndrome,
stated,  "I consider Dr. Pall's research a significant contribution to the
science of
clinical toxicology and multiple chemical sensitivity."  gheuser@...
Brain Imaging Center, University of California, Irvine, USA.

Dr. Grace Ziem, Maryland physician who practices occupational and
environmental medicine and specializes in chemically-induced illness, said,
"I feel that Dr. Pall has done the most important biochemical research and
documentation toward understanding the mechanism of neural sensitization
underlying toxic injury to the brain and this research has important
implications for treatment."
http://www.mcsrr.org/resources/articles/S3.html
DR. GRACE ZIEM'S ENVIRONMENTAL CONTROL PLAN
FOR CHEMICALLY SENSITIVE PATIENTS
16926 Eyler's Valley Road, Emmitsburg MD 21727, 301-241-4346
Albert Donnay donnay@...
*************************************************************

http://molecular.biosciences.wsu.edu/Faculty/pall.html [photo]

http://molecular.biosciences.wsu.edu/Faculty/pall/pall_cfs.htm
Novel chronic fatigue syndrome (CFS) theory finally produces detailed
explanations for many CFS observations:  [ This is a detailed summary
review, with diagrams, references, and some hyperlinks. ]

http://molecular.biosciences.wsu.edu/Faculty/pall/pall_fibro.htm
Fibromyalgia, excessive nitric oxide/peroxynitrite and excessive NMDA
activity [ detailed summary review, with 14 references, including
2. Smith J. D., Terpening C. M., Schmidt S. O. F., Gums J. G. Relief of
fibromyalgia symptoms following discontinuation of dietary excitotoxins.
Ann Pharmacotherapy 2001; 35: 702-706.
*************************************************************

Here, I list some specific items from the papers that I summarize
afterwards.

Pall, September 2002 review:

"...nitric oxide inhibition of cytochrome P450 metabolism."

"Excessive NMDA activity leading to excessive levels of nitric oxide and
peroxynitrite has been implicated in several neurodegenerative diseases
including amyotrophic lateral sclerosis [ALS], Parkinson's disease,
AIDS-related dementia, stroke, epilepsy, Huntington's disease, and
Alzheimer's disease (67-72)... "

"...volative organic solvents act in MCS by increasing NMDA activity."

"Miller and Mitzel (6) reported that many MCS patients appear to be
hypersensitive to monosodium glutamate, a potential excitotoxin that can act
to stimulate NMDA receptors (64, 66, 91)..."

"...One organic chemical often implicated in MCS-- formaldehyde... NMDA
stimulation... pain responses... by excessive NMDA activity and consequent
elevated nitric oxide levels..."

"...Donald Dudley... clinical observations on his MCS patients (131)...
known NMDA antagonist, dextromethorphan, appeared to block the effects of
organic solvents on his MCS patients... on an episodic basis... stop the
reaction before it gets started...  Two other physicians in Washington
state,Gordon Baker and David Buscher,...dextromethorphan for their MCS
patients in a similar fashion, with apparently similar results..."

"Part of the goal here is to suggest potentially important foci for
hypothesis-driven research, and clearly the many uncertainties in this part
of the hypothesis suggest many such topics of future study.

In her MCS review, [B.A.] Sorg (ref 2, Table 1) lists 18 neurological
symptoms as being found in MCS but lists other symptoms of
cardiovascular (two), respiratory (seven), gastrointestinal (three),
genitourinary (four), musculoskeletal (five), and dermatologic (one)
origin...various other organs appear to be affected in many cases...
inflammatory
cytokines... will circulate to a variety of tissues and have been reported
to be induced by organic solvents (28)... Furthermore,... nitric oxide
transport... spreading to other tissues... [ These many symptoms fit the
profile of aspartame disease. ]

2. Sorg BA.
Multiple chemical sensitivity: potential role for neural sensitization.
Crit. Rev. Neurobiol. 1999; 13: 283-316.

...organic solvent exposure is an important risk factor in Parkinson's
disease (148-153)... Excessive NMDA activity is associated with Parkinson's
disease...

...funding for MCS disease is less than a thousandth of that available for
diabetes research... critical need for clear and compelling hypotheses,
consistent with the many reported properties of MCS, to provide a basis for
future research... four proposed consequent mechanisms... are all expected
to act synergistically, producing the kind of exquisite sensitivity reported
in MCS..."

Pall, March 2001 review:

""MCS incitants...volatile organics, such as hydrocarbons, chlorinated
hydrocarbons, other organics, and pesticides...benzene (4-6), carbon
tetrachloride (7-9), formaldehyde (10-13), and chlorinated hydrocarbon
pesticides (14).  Organophosphate pesticides...Such muscarinic receptor
stimulation is known to produce increases in nitric oxide levels. (15-18)"

Pall, August 2001 review:

"...The most characteristic symptoms in FM are muscle and joint pain and
tender points.  It is well documented that nitric oxide stimulates many but
not all nociceptors (see, for example, refs 55-59) and I propose that, as in
the case of migraine headaches (58-59), much of the pain in FM may be
generated by elevated nitric oxide..."

"...symtoms of carbon monoxide (CO) toxicity include essentially all of the
overlapping symptoms typical of CFS, MCS, PTSD and FM, including fatigue,
headache, dizziness, memory impairmant, cognitive dysfunction, weakness,
vertigo and sleep deprivation (66-76).  Many victims of CO show chronic
symptoms, lasting from many months to years after both CO exposure has
terminated and CO levels in the blood have returned to normal (66, 67,
69-73)..."  [ These same symptom patterns are also characteristic of
aspartame reactors. ]

Pall, January 2000 review:

"...such disease states as atherosclerosis, myocarditis, nephritis, and a
wide variety of automimmune diseases.

...uveoretinitis... rheumatoid arthritis, type I diabetes, multiple
sclerosis, systemic lupus erythrematosis..."
************************************************************

FASEB J 2002 Sep; 16(11): 1407-17
NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and
organic solvents as the mechanism of chemical sensitivity in multiple
chemical sensitivity.
Pall ML.  [ 162 references, received 1.3.2 ]
School of Molecular Biosciences, Washington State University,
Pullman, Washington 99164-4660, USA.   martin_pall@...

http://www.fasebj.org/cgi/content-nw/full/16/11/1407/T1.  full text
Access to this site is free to members of the Federation of American
Societies of Experimental Biology. Others must pay a $7 access fee.

Multiple chemical sensitivity (MCS) is a condition where previous exposure
to hydrophobic organic solvents or pesticides appears to render people
hypersensitive to a wide range of chemicals, including organic solvents.
The hypersensitivity is often exquisite, with MCS individuals showing
sensitivity that appears to be at least two orders of magnitude greater than
that of normal individuals. This paper presents a plausible set of
interacting mechanisms to explain such heightened sensitivity.

It is based on two earlier theories of MCS: the elevated nitric
oxide/peroxynitrite theory and the neural sensitization theory.
It is also based on evidence implicating excessive NMDA activity in MCS.
Four sensitization mechanisms are proposed to act synergistically, each
based on known physiological mechanisms:
Nitric oxide-mediated stimulation of neurotransmitter (glutamate) release;
peroxynitrite-mediated ATP depletion and consequent hypersensitivity of NMDA
receptors;
peroxynitrite-mediated increased permeability of theblood-brain barrier,
producing increased accessibility of organic chemicals to the central
nervous system;
and nitric oxide inhibition of cytochrome P450 metabolism.

Evidence for each of these mechanisms, which may also be involved in
Parkinson's disease, is reviewed.
These interacting mechanisms provide explanations for diverse aspects of MCS
and a framework for hypothesis-driven MCS research.   PMID: 12205032

"...exposure to organophosphates or carbamates (1-7)...hypersensitive...
hydrophobic, volatile organic solvents... not to be centered on an IgE-based
allergic mechanism (1)... severe MCS in the U.S. is ~4% with greatly reduced
quality of life for the patient (2)...less severe problems have been
reported in ~15-30% of the population...chemical sensitivity two or more
orders of magnitude greater than do normal individuals... no known mechanism
whereby low levels of chemical or chemicals of widely varied chemical
structure can interact adversely with numerous organ systems... Chronic
fatigue syndrome (CFS), fibromyalgia (FM), and post-traumatic stress
disorder (PTSD)...overlapping symptoms... preceded by short-term stress,
only to be followed by a chronic condition that typically lasts for years or
decades. Gulf War syndrome... may share a common etiologic mechanism
(16,23-29)...elevated nitric oxide/peroxynitrite mechanism
(28-33)...short-term stress...increases in nitric oxide (29-32)... reacts
with superoxide to form the
potent oxidant peroxynitrite... six different positive feedback loop
mechanisms to increase the levels of nitric oxide and its other precursor,
superoxide, which in turn react to form more peroxynitrite (30)...
biochemical vicious cycle is initiated and maintained that produces the
chronic nature of these four conditions...10 types of supportive evidence
are summarized in Table 1...

The second precursor theory to this paper is the neural sensitization theory
origianlly proposed by Bell and co-workers (34)...
[ 34. Iris R. Bell, Miller CS, Schwartz GE.(1992).
An olfactory-limbic model of multiple chemical sensitivity syndrome:
possible relationships to kindling and affective spectrum disorders.
Biol. Psychiatry 1992; 32: 218-242.

35. Bell IR, Baldwin CM, Fernandez M, Schwartz GE.
Neural sensitization model for multiple chemical sensitivity: overview
of theory and empirical evidence.
Toxicol Ind. Health 1999; 15: 295-304. ]

... especially the limbic system... increased long-term synaptic sensitivity
induced by previous electrical and chemical stimulation...long-term
potentiation (LTP)... nitric oxide and the NMDA [ N-methyl-D-aspartame ]
excitatory neurotransmission system are implicated in LTP, the presumed
mechanism of neural sensitization...increased Ca2+ influx into the cell...
Excessive NMDA activity leading to excessive levels of nitric oxide and
peroxynitrite has been implicated in several neurodegenerative diseases
including amyotrophic lateral sclerosis [ALS], Parkinson's disease,
AIDS-related dementia, stroke, epilepsy, Huntington's disease, and
Alzheimer's disease (67-72)... nitric oxide and peroxynitrite may act
through known mechanisms to increase both the stimulation of and the
sensitivity of NMDA receptors.

...volative organic solvents act in MCS by increasing NMDA activity. The
evidence for this (discussed below) is suggestive but not conclusive...
leading to ATP [ adenosine triphosphate, a primary energy store and source
in cells ] depletion as well... when neurons containing NMDA receptors have
lowered ATP pools, their NMDA receptors become hypersensitive to
stimulation... MCS individuals are often reported to have low Mg2+ pools
(7), and Mg2+ is known to lower NMDA sensitivity (91).

...Acetylcholline will activate the muscarinic receptors, which are known to
produce increases in nitric oxide... people in buildings that had been
remodeled ("sick building syndrome"), thus exposing the individuals to
outgassing of organic solvents from the building materials... (infection,
physical trauma, and stress) may act to increase nitric oxide levels
(29,30,32)... carbon monoxide... chronic sequelae (29), with symptoms
similar to those in CFS, and carbon monoxide is reported to induce excessive
production of the two percursors of peroxynitrite: superoxide and nitric
oxide (29).

Peroxynitrite... to increase the permeability of the blood-brain barrier in
MCS... to increase chemical access to the CNS and thus increase chemical
sensitivity generated in the CNS...

Miller and Mitzel (6) reported that many MCS patients appear to be
hypersensitive to monosodium glutamate, a potential excitotoxin that can act
to stimulate NMDA receptors (64, 66, 91)...

One organic chemical often implicated in MCS-- formaldehyde... NMDA
stimulation... pain responses... by excessive NMDA activity and consequent
elevated nitric oxide levels...

...Donald Dudley... clinical observations on his MCS patients (131)... known
NMDA antagonist, dextromethorphan, appeared to block the effects of organic
solvents on his MCS patients... on an episodic basis... stop the reaction
before it gets started...  Two other physicians in Washington state,Gordon
Baker and David Buscher,...dextromethorphan for their MCS patients in a
similar fashion, with apparently similar results...

Part of the goal here is to suggest potentially important foci for
hypothesis-driven research, and clearly the many uncertainties in this part
of the hypothesis suggest many such topics of future study.

In her MCS review, [B.A.] Sorg (ref 2, Table 1) lists 18 neurological
symptoms as being found in MCS but lists other symptoms of cardiovascular
(two), respiratory (seven), gastrointestinal (three), genitourinary (four),
musculoskeletal (five), and dermatologic (one) origin... various other
organs appear to be affected in many cases... inflammatory cytokines... will
circulate to a variety of tissues and have been reported to be induced by
organic solvents (28)... Furthermore,... nitric oxide transport... spreading
to other tissues... [ These many symptoms fit the profile of aspartame
disease. ]

2. Sorg BA.
Multiple chemical sensitivity: potential role for neural sensitization.
Crit. Rev. Neurobiol. 1999; 13: 283-316.

...organic solvent exposure is an important risk factor in Parkinson's
disease (148-153)... Excessive NMDA activity is associated with Parkinson's
disease...

...funding for MCS disease is less than a thousandth of that available for
diabetes research... critical need for clear and compelling hypotheses,
consistent with the many reported properties of MCS, to provide a basis for
future research... four proposed consequent mechanisms... are all expected
to act synergistically, producing the kind of exquisite sensitivity reported
in MCS...

I thank Drs. James Satterlee, 'Jay" Wright and Joseph Harding for helpful
discussions."
*************************************************************

28. Pall ML, Satterlee JD.
Elevated nitric oxide/peroxynitrite mechanism for the common etiology
of multiple chemical sensitivity, chronic fatigue syndrome, and
posttraumatic stress disorder.
Ann N Y Acad Sci. 2001 Mar; 933: 323-9. Review. [ 45 references ]

Various types of evidence implicate nitric oxide and an oxidant, possibly
peroxynitrite, in MCS and chemical intolerance (CI).
The positive feedback loops proposed earlier for CFS may explain the chronic
nature of MCS (CI) as well as several of its other reported properties.
These observations raise the possibility that this proposed elevated
nitric oxide/peroxynitrite mechanism may be the mechanism of a new disease
paradigm, answering the question raised by Miller earlier:
"Are we on the threshold of a new theory of disease?"
Publication Types: Review Review, Tutorial PMID: 12000033

"MCS incitants...volatile organics, such as hydrocarbons, chlorinated
hydrocarbons, other organics, and pesticides...benzene (4-6), carbon
tetrachloride (7-9), formaldehyde (10-13), and chlorinated hydrocarbon
pesticides (14).  Organophosphate pesticides...Such muscarinic receptor
stimulation is known to produce increases in nitric oxide levels. (15-18)

...elevated neopterin levels...a biochemical marker...

In one study, several antioxidants were used to treat patients with MCS,
with some apparent success, (23), suggesting that oxidative damage may have
a role in MCS...blood of MCS patients...elevated levels of oxidants...the
serum to have lower levels of antioxidants, as compared to controls, (24)...

...stimulation of the limbic system...spontaneous seizures (kindling).
(25-29) ... inhibitor of nitric oxide synthase activity blocked the
characteristic sensitization response. (30-36)...arginine,...stimulated the
response. (32)...nitric oxide has an essential role in producing neural
sensitization and kindling...MCS."
************************************************************

29. Pall ML.
Common etiology of posttraumatic stress disorder, fibromyalgia, chronic
fatigue syndrome and multiple chemical sensitivity via elevated nitric
oxide/peroxynitrite. [ 93 references, received 10.19.0 ]
Med Hypotheses. 2001 Aug; 57(2): 139-45.

Three types of overlap occur among the disease states chronic fatigue
syndrome (CFS), fibromyalgia (FM), multiple chemical sensitivity (MCS)
and posttraumatic stress disorder (PTSD).
They share common symptoms.

Many patients meet the criteria for diagnosis for two or more of these
disorders and each disorder appears to be often induced by a relatively
short-term stress which is followed by a chronic pathology, suggesting
that the stress may act by inducing a self-perpetuating vicious cycle.

Such a vicious cycle mechanism has been proposed to explain the
etiology of CFS and MCS, based on elevated levels of nitric oxide and
its potent oxidant product, peroxynitrite.
Six positive feedback loops were proposed to act such that when
peroxynitrite levels are elevated, they may remain elevated.
The biochemistry involved is not highly tissue-specific, so that variation
in symptoms may be explained by a variation in nitric oxide/peroxynitrite
tissue distribution.

The evidence for the same biochemical mechanism in the etiology of PTSD
and FM is discussed here, and while less extensive than in the case of
CFS and MCS, it is nevertheless suggestive.
Evidence supporting the role of elevated nitric oxide/peroxynitrite in these
four disease states is summarized, including induction of nitric oxide by
common apparent inducers of these disease states, markers of elevated nitric
oxide/peroxynitrite in patients and evidence for an inductive role of
elevated nitric oxide in animal models.

This theory appears to be the first to provide a mechanistic explanation
for the multiple overlaps of these disease states and it also explains
the origin of many of their common symptoms and similarity to both Gulf
War syndrome and chronic sequelae of carbon monoxide toxicity.
This theory suggests multiple studies that should be performed to further
test this proposed mechanism.
If this mechanism proves central to the etiology of these four conditions,
it may also be involved in other conditions of currently obscure etiology
and criteria are suggested for identifying such conditions.  PMID: 11461161

"...The NMDA receptors are receptors for the amino acid glutamate and the
toxicity of excessive glutamate is mediated through these receptors and
specifically through their action in increasing the synthesis of both nitric
acid and peroxynitrite (20-26).  In animal models of PTSD, severe stress
induces considerable oxidative damage, probably through the action of
peroxynitrite-induced oxidative chain reactions. Reported oxidative changes
include glutathione depletion, increases in lipid peroxide levels and
changes in the levels of antioxidant enzymes (27-29)...

...The most characteristic symptoms in FM are muscle and joint pain and
tender points.  It is well documented that nitric oxide stimulates many but
not all nociceptors (see, for example, refs 55-59) and I propose that, as in
the case of migraine headaches (58-59), much of the pain in FM may be
generated by elevated nitric oxide...

...Tissue hypoxia generated by excessive exercise...through increased
synthesis of superoxide, the other precusor of peroxynitrite (12 and see
below.)...

...symtoms of carbon monoxide (CO) toxicity include essentially all of the
overlapping symptoms typical of CFS, MCS, PTSD and FM, including fatigue,
headache, dizziness, memory impairmant, cognitive dysfunction, weakness,
vertigo and sleep deprivation (66-76).  Many victims of CO show chronic
symptoms, lasting from many months to years after both CO exposure has
terminated and CO levels in the blood have returned to normal (66, 67,
69-73)... [ These same symptom patterns are also characteristic of aspartame
reactors. ]

I suggest nine such criteria:
1. A pattern of possible induction by a short-term stress preceding a
chronic pathology.
2. Uncertain etiology.
3. Association with CFS, MCS, FM and/or PTSD.
4. Elevated tissue levels of nitric oxide/peroxynitrite.
5. Elevated levels of inflammatory cytokines.
6. Elevated levels of oxidants and lowered levels of antioxidants.
7. Chronic inflammation.
8. Chemical hypersensitivity.
9. Effective treatment wtih local glucocorticoid exposure.

...Glucocorticoids are used to treat such diseases as asthma and psoriasis
and are known to repress the synthesis of the inductible nitric oxide
synthase (92, 93). [ This gives many suggestions for biochemical assays and
treatments for aspartame reactors. ]

...grant from the Air Force Office for Scientific Research."
*************************************************************

30. Pall ML.
Elevated, sustained peroxynitrite levels as the cause of chronic
fatigue syndrome. [ 125 references, received 7.29.98 ]
Med Hypotheses. 2000 Jan; 54(1): 115-25.

The etiology of chronic fatigue syndrome (CFS) has been both obscure and
highly contentious, leading to substantial barriers to both clear diagnosis
and effective treatment.
I propose here a novel hypothesis of CFS in which either viral or bacterial
infection induces one or more cytokines, IL-1beta IL-6, TNF-alpha and
IFN-gamma.

These induce nitric oxide synthase(iNOS), leading to increased nitric oxide
levels. Nitric oxide, in turn, reacts with superoxide radical to generate
the potent oxidant peroxynitrite.

Multiple amplification and positive feedback  mechanisms are proposed by
which once peroxynitrite levels are elevated, they tend to be sustained at a
high level.
This proposed mechanism may lower the HPA axis activity and be maintained by
consequent lowered glucocorticoid levels.
Similarities are discussed among CFS and autoimmune and other diseases
previously shown to be associated with elevated peroxynitrite.
Multiple pharmacological approaches to the treatment of CFS are suggested by
this hypothesis.  PMID: 10790736

"...widely discussed notion that post-viral fatigue syndrome (2) is a form
of chronic fatigue syndrome... overall notion of post-infectious fatigue
syndrome (4)....

"Peroxynitrite, OONO-, is a powerful oxidant formed from the reaction of two
relatively nonreactive free radicals, nitric oxide (*NO) and superoxide
(*OO-)... (10-12)... Nitric oxide is synthesized by three different isozymes
of nitric oxide synthase, two of which are constitutive, eNOS and nNOS and
one of which is highly inducible, iNOS.  It is the inducible iNOS isozyme
which has the most central role in this hypothesis. iNOS is higly induced in
many cell types in response to four different inflammatory cytokines...
which are, in turn, induced by viral infection or the presence of bacterial
antigens... infections can lead to the induction of high levels of iNOS,
greatly increasing the levels of nitric oxide and leading to a great
increase in the levels of peroxynitrite... this occurs in sepsis...
mitochondrial and energy metabolism dysfunction is one of the most important
consequences of elevated peroxynitrite (10, 11, 21-23).

...increasing Ca2+ levels will increase nitric oxide synthesis...

...such disease states as atherosclerosis, myocarditis, nephritis, and a
wide variety of automimmune diseases.

...uveoretinitis... rheumatoid arthritis, type I diabetes, multiple
sclerosis, systemic lupus erythrematosis... each show their own
characteristic distribution of peroxynitrite elevation as shown by such
measures as nitrotyrosine distribution in proteins or iNOS expression
pattern... A number of reports suggest that the
hypothalamic-pituitary-adrenal (HPA) axis may have lowered activity in CFS
patients and that this lowered activity may be responsible for many of the
characteristic symptoms of CFS (5, 47-55).  These reports suggest that
lowered responsiveness of the hypothalalmus may be an important cause of CFS
and that the resulting lowered levels of glucocorticoids may be responsible
for many of the symptoms of CFS... What is intriguing, however is that the
low levels of glucocorticoids, produced by low HPA axis activity in CFS
patients, may have a substantial role in the proposed sustained elevation of
both inflammatory cytokine levels and nitric oxide/peroxynitrite levels.
Glucorticoids have long been known to suppress both immune and inflammatory
responses... to inhibit induction of both the inducible nitric oxide
synthase (iNOS) in multiple tissues and also the induction of the
inflammatory cytokines...

...one of the primary targets of peroxynitrite is the mitochodrion...This
predicts that energy metabolism disfunction should be characteristic of
CFS... measurements of phosphorylation activity... mitochondrial structural
changes as seen in the electron microscope (78-84)... urine of CFS
patients... two TCA cycle intermediates, succinate and cis-aconitate, were
both found to be elevated in CFS patients (85, 86)... succinic dehydrogenase
activity...has been reported to be low (78, 80)...  [ Unrelenting fatigue is
often part of aspartame disease. ]  ...a CFS patient who had accumulated
unusual deletions in his mitochondrial DNA (82)....  [ Formaldehyde from
the 11% methanol component of aspartame forms DNA adducts. ]

...polyunsaturated essential fatty acids are low in CFS patients (87) may
also be explained because the lipid peroxidation induced by elevated
peroxynitrite (10-12, 22) preferentially oxidizes such polyunsaturated fatty
acids...

...CFS patients have been reported to suffer from low NK syndrome,
characterized by low serum levels of cystine and glutamine (88).  Low NK
syndrome is also found in several diseases characterized by elevated
peroxynitrite levels, including sepsis, Crohn's disease, ulcerative colitis,
AIDS dementia patients and some forms of cancer (89)...

...possible pharmacological intervention...
1. ...ubiquinone (coenzyme Q10) and carnitine may improve mitochondrial
function in CFS....
2. Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin and
ibuprofen, have been reported to inhibit iNOS induction (91,92)...
3. Cell permeable superoxide dismutase mimetic agents...such as MnTBAP to
lower superoxide levels (93, 94)...
4. ...lower the induction of iNOS... vitamin D derivatives (95),
epigallocatechin-3-gallate and genistein... protein tyrosine kinase
inhibitors... linomide, a drug used to treat autoimmune disease (101), and
terpenoids (102).
5. ...antioxidants...
a. ...gamma-tocopherol...
b. N-acetyl cysteine...
c. Flavonoids... epigallocatechin gallate (107)... and genistein...
These two are found in high amounts in green tea and soy products,
respectively....
d. Ascorbic acid acts as a peroxynitrite scavenger, in addition to its
general activity as an antioxidant (108, 109)....
e. Many antioxidants have been shown to inhibit NF-kB activity...
6. Arginine... inhibit... nitric oxide synthrase enzymes... (19,20)...
7. ...Some inhibitors of NF-kB activity, such as TLCK or PDTC, act
indirectly as protease inhibitors or by other mechanisms... (113, 114).
...genistein...
8. Allopurinol is a well-documented inhibitor of xanthine
oxidase/xanthine dehydrogenase activity and has been widely used to
treat gout and other diseases... numerous flavonoids...
9. ...inhibitors of this enzyme... poly(ADP-ribose) synthase... have been
shown to improve cellular survival when challenged by peroxynitrite (36-38).

This paper is dedicated to the memory of Stephanie Pall.

...neopterin levels are elevated to the urine or serum of CFS patients (66,
119, 120)... closely linked to the induction of the inducible nitric oxide
synthase (123-125)... important, if indirect, evidence for nitric oxide
elevation in CFS patients..."
************************************************************

31. Pall, ML.
Levels of nitric oxide synthase product citrulline are elevated in sera
of chronic fatigue syndrome patients.
J. Chronic Fatigue Syndr. 2002; 10(3/4): 37-41. [ 7 references ]

www.cfs.inform.dk/
http://www.cfs.inform.dk/Hypoteser/pall02.pdf  free full text

Serum levels of citrulline, a product of nitric oxide synthase activity,
were measured in 36 CFS patients.

Serum citrulline levels were found to be significantly eleveated in CFS
patients and, in addition, there was a trend towards higher levels in CFS
patients with stronger symptoms.

These results provide support for the view that nitric oxide synthesis
activity tends to be elevated in CFS patients, thus supporting a prediction
of the elevated nitric oxide/peroxynitrite theory of CRS etiology.

"INTRODUCTION
Chronic fatigue syndrome (CFS) is reported to impact a large number of
different biochemical, physiological and immunological properties in
patients, ranging from mitochondrial/energy metabolism to circulatory
function to neuroendocrine function to natural killer cell function
(discussed in 1,2). Similarly a wide range of symptoms are commonly reported
(3). One of the central questions facing CFS researchers is how these
diverse characteristics may be impacted by a single etiologic mechanism.

A wide-ranging theory of CFS is the elevated nitric oxide/peroxynitrite
theory, which is supported by 12 different biochemical/physiological
observations about CFS (1,2,4) and explains many of the diverse symptoms in
this condition through known biochemical and physiological mechanisms (2).

The same basic etiology may also explain the properties of three conditions
that overlap with CFS: multiple chemical sensitivity, fibromyalgia and
posttraumatic stress disorder (5,6).

According to this theory, CFS is initiated by stresses such as infection
that lead to elevated levels of nitric oxide and its oxidant product,
peroxynitrite. Peroxynitrite acts through several positive feedback loops to
elevate the levels of both of its precursors, nitric oxide and superoxide,
which will then react with each other to form more peroxynitrite. In this
way, a biochemical vicious cycle is initiated and maintained with that
vicious cycle being responsible for the chronic nature of CFS.

According to this view, infection acts by inducing inflammatory cytokines
which induce, in turn, the inducible nitric oxide synthase (iNOS). However,
the chronic phase of CFS may be maintained through the action of both iNOS
and the other nitric oxide synthase isozymes, nNOS and eNOS (1). A number of
studies have reported that during the chronic phase of CFS, both
inflammatory cytokines that induce the iNOS gene are elevated and that the
marker for iNOS activity, neopterin levels, are also elevated in CFS
(references in 1,2,4). However, because both iNOS and the other NOS isozymes
are proposed to be involved in the chronic phase of CFS, it is important to
measure a marker of overall nitric oxide synthesis, not just iNOS activity.

Because nitric oxide is unstable in vivo, nitric oxide synthase activity in
vivo is usually measured by either of two different markers. Either
nitrate/nitrite levels are measured because these are produced through the
degradation of nitric oxide and its oxidant product, peroxynitrite, or
L-citrulline levels are measured.

Because nitrate/nitrite levels are elevated by diets including such foods as
green vegetables and sausages and other preserved meat and fish products, it
is essential to closely control the diet of people for whom nitrate/nitrite
measurements are to reflect NOS activity.

Citrulline, the coproduct of nitric oxide synthase activity, is stable and
its levels are much less likely to be perturbed by diet, as compared with
nitrate/nitrite, and may therefore be a preferred measurement for this
reason. In a recent study by Larson et al. (7), the citrulline levels in the
cerebrospinal fluid of fibromyalgia patients were reported to be elevated,
allowing them to infer that nitric oxide synthesis was elevated in the
central nervous systems of fibromyalgia patients as compared with controls.
In the current study, the serum levels of citrulline of CFS patients are
compared with those of controls and also found to be elevated."

"7. Larson AA, Glovengo SL, Russell U, et al. Changes in the
concentration of amino acids in the cerebrospinal fluid that correlate
with pain in patients with fibromyalgia. Pain 2000; 87: 201-211."
************************************************************

33. Pall ML.
Cobalamin [vitamin B12] used in chronic fatigue syndrome therapy is a
nitric oxide scavenger.
J. Chronic Fatigue Syndr. 2001; 8(2): 39-44. [ 38 references ]

Cobalamin (vitamin B12) in the form of hydrooxocobalamin or cyanocobalamin
injections has been widely used to treat chronic fatigue syndrome (CFS).

Hydroxocobalamin is a nitric oxide scavenger and is proposed here to act
as such a scavenger in CFS treatment.
Its possible efficacy in CFS treatment, if further substantiated, may
provide confirmation of a prediction of the elevated nitric
oxide/peroxynitrite theory of CFS etiology.
This interpretation of the possible role of cobalamin in CFS treatment
suggests a useful perspective for confirming and optimizing this treatment.
************************************************************

http://www.immunesupport.com/library/showarticle.cfm?ID=2976
http://www.imunologie.cz/kveten01_6.htm
New Theory on Explanations for Chronic Fatigue Syndrome
by Dr. Martin L. Pall   http://www.ImmuneSupport.com

02-13-2001 Editor's Note: Dr. Martin L. Pall, Ph.D., received his Ph.D. in
Biochemistry and genetics from Caltech after receiving his B.A. degree at
Johns Hopkins University. He is a professor of biochemistry and Basic
Medical Sciences at Washington State University. He teaches medical students
and is the chief instructor at Washington State University in the medical
biochemistry course for first year medical students.

Dr. Pall writes that he came down with CFS in June/July 1997 after a severe
bout of Varicella zoster infection. "My CFS was diagnosed by my primary care
physician and my case did meet the 1994 CDC criteria. So this was, in many
ways, a typical case of post-viral fatigue syndrome, sudden onset. However,
I have had an excellent recovery, over about a year and a half (possibly due
to self-medication?), and consider myself cured. So, I don't view myself as
a CFS patient. It was only after recovery from the severe cognitive
dysfunction that I was able to dedicate myself to understanding the basis of
CFS."

I asked Dr. Pall about his comment that he considers himself cured. Is he
not afraid of a relapse in the future? Also, to what does he attribute the
'cure' and how does he stay healthy? This is his response:

I became ill with CFS in June/July 1997 and spent most of July and August in
bed trying to recuperate. The following semester, I was able to perform at a
minimal level in my teaching, taking lot's of sick leave, living from day to
day, as most of us do. I self medicated on several things (more about that
later) but had little apparent improvement.  However, the following winter,
I did improve substantially and by May was doing very well, not completely
recovered but maybe 80% recovered. A year later, I considered myself
completely recovered although I am still self-medicating, not wanting to
take any chances of having a relapse.

Specifically, over the past two summers, I have been able togo on a series
of fairly taxing Sierra Club hikes with no post-exertional malaise. That is
quite distinct from my earlier condition where I could only walk (slowly)
circa 50 yards before having to sit down for a long rest.

My self medication was primarily with antioxidants (natural mixed
tocopherols, vitamin C, selenium, some carotenoids, calcium/magnesium
supplement, Ginkgo extract and coenzyme Q10). I also tried some black
currant seed oil and some choline/inositol supplements - I did not think
these helped but maybe I was wrong? I am very careful with my diet, eating
nutritionally rich foods and antioxidant-rich foods (it would take a book to
tell you all about the food issue). I did not have any GI tract problems so
was able to tolerate both the supplements and a wide variety of foods.

The most dramatic effects that I saw, appeared to be from the Ginkgo extract
(this over a period of two or more months, however) and, following that,
from the Co Q10 , the latter of which was a dramatic, within 24 hours,
recovery of cognitive function. I have never had a problem with cognitive
dysfunction since that time and am still taking the Co Q10. I am aware that
most others who have tried Co Q10 have not had as favorable a response, and
I can only think that my body was primed, possibly by the other supplements
and foods, to be ready to respond to it.

I have been running a clinical trial/pilot study with a physician (Dr.
Albert G. Corrado) using a series of supplements based on my theory, and the
results have been both encouraging and discouraging -- encouraging because
essentially everyone who was on the trial and was able to tolerate most of
the supplements reported an improvement but all reported a modest
improvement, over a 150 day period. So no one was cured over that time. I
met yesterday with a group of PWCS [Persons With Chemical Sensitivity], a
few of whom were on the trial, and we are seeing some continued improvement
(most people opted to continue on the supplements after the trial was
officially completed, suggesting that they felt that the supplements were
helpful). One person even reported that she was "almost normal" now about 13
months after starting on the supplements. So, maybe there is hope.

With regard to your question about a possible relapse, that is, of course,
the nightmare of all us who have largely or partially recovered from CFS.
All I can say is that over the past two years, I have functioned on a
completely normal level -- but then, I am still self-medicating and plan to
continue doing so indefinitely. Some of the hikes I have been on have been
quite taxing -- 8 1/2 to 9 mile fairly tough hikes, with substantial
elevation gains -- and the results have been some fatigue afterwards, but
normal fatigue, just requiring normal resting. So I am hopeful that this
functional recovery is permanent.

Novel chronic fatigue syndrome (CFS) theory finally produces detailed
explanations for many CFS observations

A novel theory of the cause of CFS has been published which is supported by
diverse biochemical and physiological observations of CFS, while providing
explanations for five of most difficult puzzles about this medical
condition. The theory has been published by Dr. Martin L. Pall (Professor of
Biochemistry and Basic Medical Sciences, Washington State University) in
several publications (1-4,9).

The theory starts with the observation that infections that precede and may
therefore induce CFS and related conditions act to induce excessive
production of inflammatory cytokines that induce, in turn, the inducible
nitric oxide synthase (iNOS). This enzyme, in turn, synthesizes excessive
amounts of nitric oxide which reacts with another compound (superoxide) to
produce the potent oxidant peroxynitrite. Peroxynitrite acts via six known
biochemical mechanisms to increase the levels of both nitric oxide and
superoxide which react to produce more peroxynitrite. In this way, once
peroxynitrite levels are elevated, they may act to continue the elevation,
thus producing a self-sustaining vicious cycle. It is this cycle, according
to the theory, that maintains the chronic symptoms of CFS and it is this
cycle, therefore, that must be interrupted to effectively treat this
condition.
************************************************************

http://www.ImmuneSupport.com/library/showarticle.cfm/id/4072
The Poisoning of America: The Rise of 'Mystery' Illnesses Including Chronic
Fatigue Syndrome, Fibromyalgia, and Gulf War Syndrome ImmuneSupport.com
11-13-2002    By Jason Alexander Uttley
"Gulf War Syndrome... Fibromyalgia... Chronic Fatigue Syndrome... At the
heart of this horrific story lies a group of antibiotics called the
fluoroquinolones. Among the more common of these medications are:
ciprofloxacin (Cipro), levofloxacin (Levaquin), norfloxacin (Noroxin),
ofloxacin (Floxin), and trovafloxacin (Trovan).... Such conditions include
Irritable Bowel Syndrome, Multiple Chemical Sensitivity Syndrome, Chronic
Myofascial Pain Syndrome, and Peripheral Neuropathy.... Just like all the
other conditions mentioned previously their symptoms often include: joint
pain, muscle stiffness/aches, tendon pain, dizziness, disorientation,
burning and tingling sensations, numbness, diarrhea, sensory sensitivities,
and brain fog." [ All these symptoms are common in aspartame disease.  This
suggests that Pall may be on the right track with a theory that many CFS
type diseases share a common etiology. ]
************************************************************

http://www.healthyplace.com/Communities/Thought_Disorders/schizo/articles/schizo\
phrenia_brain.htm

Decoding Schizophrenia: A fuller understanding of signaling in the brain of
people with schizophrenia offers new hope for improved therapy
by Daniel C. Javitt and Joseph T. Coyle   Scientific American  January 2004
p. 48-55.

INNER WORLD of people with schizophrenia is often confused, punctuated by
alien voices, paranoia and illogical thoughts.

(Dec. 15, 2003) -- Today the word "schizophrenia" brings to mind such names
as John Nash and Andrea Yates. Nash, the subject of the Oscar-winning film A
Beautiful Mind, emerged as a mathematical prodigy and eventually won a Nobel
Prize for his early work, but he became so profoundly disturbed by the brain
disorder in young adulthood that he lost his academic career and floundered
for years before recovering. Yates, a mother of five who suffers from both
depression and schizophrenia, infamously drowned her young children in a
bathtub to "save them from the devil" and is now in prison.

The experiences of Nash and Yates are typical in some ways but atypical in
others. Of the roughly 1 percent of the world's population stricken with
schizophrenia, most remain largely disabled throughout adulthood. Rather
than being geniuses like Nash, many show below- average intelligence even
before they become symptomatic and then undergo a further decline in IQ when
the illness sets in, typically during young adulthood.

Unfortunately, only a minority ever achieve gainful employment. In contrast
to Yates, fewer than half marry or raise families. Some 15 percent reside
for long periods in state or county mental health facilities, and another 15
percent end up incarcerated for petty crimes and vagrancy. Roughly 60
percent live in poverty, with one in 20 ending up homeless. Because of poor
social support, more individuals with schizophrenia become victims than
perpetrators of violent crime.

Medications exist but are problematic. The major options today, called
antipsychotics, stop all symptoms in only about 20 percent of patients.
(Those lucky enough to respond in this way tend to function well as long as
they continue treatment; too many, however, abandon their medicines over
time, usually because of side effects, a desire to be "normal" or a loss of
access to mental health care). Two thirds gain some relief from
antipsychotics yet remain symptomatic throughout life, and the remainder
show no significant response.

An inadequate arsenal of medications is only one of the obstacles to
treating this tragic disorder effectively. Another is the theories guiding
drug therapy. Brain cells (neurons) communicate by releasing chemicals
called neurotransmitters that either excite or inhibit other neurons. For
decades, theories of schizophrenia have focused on a single
neurotransmitter: dopamine. In the past few years, though, it has become
clear that a disturbance in dopamine levels is just a part of the story and
that, for many, the main abnormalities lie elsewhere. In particular,
suspicion has fallen on deficiencies in the neurotransmitter glutamate.
Scientists now realize that schizophrenia affects virtually all parts of the
brain and that, unlike dopamine, which plays an important role only in
isolated regions, glutamate is critical virtually everywhere. As a result,
investigators are searching for treatments that can reverse the underlying
glutamate deficit.

Multiple Symptoms
To develop better treatments, investigators need to understand how
schizophrenia arises--which means they need to account for all its myriad
symptoms. Most of these fall into categories termed "positive," "negative"
and "cognitive." Positive symptoms generally imply occurrences beyond normal
experience; negative symptoms generally connote diminished experience.
Cognitive, or "disorganized," symptoms refer to difficulty maintaining a
logical, coherent flow of conversation, maintaining attention, and thinking
on an abstract level.

The public is most familiar with the positive symptoms, particularly
agitation, paranoid delusions (in which people feel conspired against) and
hallucinations, commonly in the form of spoken voices. Command
hallucinations, where voices tell people to hurt themselves or others, are
an especially ominous sign: they can be difficult to resist and may
precipitate violent actions.

PERCEIVING FRAGMENTS as parts of a whole can be difficult for people with
schizophrenia. When normal subjects view fractured images like those above
in sequence, they identify the object quickly, but schizophrenic patients
often cannot make that leap swiftly.

The negative and cognitive symptoms are less dramatic but more pernicious.
These can include a cluster called the 4 A's: autism (loss of interest in
other people or the surroundings), ambivalence (emotional withdrawal),
blunted affect (manifested by a bland and unchanging facial expression), and
the cognitive problem of loose association (in which people join thoughts
without clear logic, frequently jumbling words together into a meaningless
word salad). Other common symptoms include a lack of spontaneity,
impoverished speech, difficulty establishing rapport and a slowing of
movement. Apathy and disinterest especially can cause friction between
patients and their families, who may view these attributes as signs of
laziness rather than manifestations of the illness.

When individuals with schizophrenia are evaluated with pencil-and-paper
tests designed to detect brain injury, they show a pattern suggestive of
widespread dysfunction. Virtually all aspects of brain operation, from the
most basic sensory processes to the most complex aspects of thought are
affected to some extent. Certain functions, such as the ability to form new
memories either temporarily or permanently or to solve complex problems, may
be particularly impaired. Patients also display difficulty solving the types
of problems encountered in daily living, such as describing what friends are
for or what to do if all the lights in the house go out at once. The
inability to handle these common problems, more than anything else, accounts
for the difficulty such individuals have in living independently. Overall,
then, schizophrenia conspires to rob people of the very qualities they need
to thrive in society: personality, social skills and wit.

Beyond Dopamine
The emphasis on dopamine-related abnormalities as a cause of schizophrenia
emerged in the 1950s, as a result of the fortuitous discovery that a class
of medication called the phenothiazines was able to control the positive
symptoms of the disorder. Subsequent studies demonstrated that these
substances work by blocking the functioning of a specific group of
chemical-sensing molecules called dopamine D2 receptors, which sit on the
surface of certain nerve cells and convey dopamine's signals to the cells'
interior. At the same time, research led by the recent Nobel laureate Arvid
Carlsson revealed that amphetamine, which was known to induce hallucinations
and delusions in habitual abusers, stimulated dopamine release in the brain.
Together these two findings led to the "dopamine theory," which proposes
that most symptoms of schizophrenia stem from excess dopamine release in
important brain regions, such as the limbic system (thought to regulate
emotion) and the frontal lobes (thought to regulate abstract reasoning).

Over the past 40 years, both the strengths and limitations of the theory
have become apparent. For some patients, especially those with prominent
positive symptoms, the theory has proved robust, fitting symptoms and
guiding treatment well. The minority of those who display only positive
manifestations frequently function quite well--holding jobs, having families
and suffering relatively little cognitive decline over time--if they stick
with their medicines.

Yet for many, the hypothesis fits poorly. These are the people whose
symptoms come on gradually, not dramatically, and in whom negative symptoms
overshadow the positive. The sufferers grow withdrawn, often isolating
themselves for years. Cognitive functioning is poor, and patients improve
slowly, if at all, when treated with even the best existing medications on
the market.

OBJECTS often have hidden meanings to people with schizophrenia, who may
hoard news items, pictures or other things that would seem useless to
others. This wall is a re-creation.

Such observations have prompted some researchers to modify the dopamine
hypothesis. One revision suggests, for example, that the negative and
cognitive symptoms may stem from reduced dopamine levels in certain parts of
the brain, such as the frontal lobes, and increased dopamine in other parts
of the brain, such as the limbic system. Because dopamine receptors in the
frontal lobe are primarily of the D1 (rather than D2) variety, investigators
have begun to search, so far unsuccessfully, for medications that stimulate
D1 receptors while inhibiting D2s.

In the late 1980s researchers began to recognize that some pharmaceuticals,
such as clozapine (Clozaril), were less likely to cause stiffness and other
neurologic side effects than older treatments, such as chlorpromazine
(Thorazine) or haloperidol (Haldol), and were more effective in treating
persistent positive and negative symptoms. Clozapine, known as an atypical
antipsychotic, inhibits dopamine receptors less than the older medications
and affects the activity of various other neurotransmitters more strongly.
Such discoveries led to the development and wide adoption of several newer
atypical antipsychotics based on the actions of clozapine (certain of which,
unfortunately, now turn out to be capable of causing diabetes and other
unexpected side effects). The discoveries also led to the proposal that
dopamine was not the only neurotransmitter disturbed in schizophrenia;
others were involved as well.

Theories focusing largely on dopamine are problematic on additional grounds.
Improper dopamine balance cannot account for why one individual with
schizophrenia responds almost completely to treatment, whereas someone else
shows no apparent response. Nor can it explain why positive symptoms respond
so much better than negative or cognitive ones do. Finally, despite decades
of research, investigations of dopamine have yet to uncover a smoking gun.
Neither the enzymes that produce this neurotransmitter nor the receptors to
which it binds appear sufficiently altered to account for the panoply of
observed symptoms.

The Angel Dust Connection
If dopamine cannot account well for schizophrenia, what is the missing link?
A critical clue came from the effects of another abused drug: PCP
(phencyclidine), also known as angel dust. In contrast to amphetamine, which
mimics only the positive symptoms of the disease, PCP induces symptoms that
resemble the full range of schizophrenia's manifestations: negative and
cognitive and, at times, positive. These effects are seen not just in
abusers of PCP but also in individuals given brief, low doses of PCP or
ketamine (an anesthetic with similar effects) in controlled drug-challenge
trials.

Such studies first drew parallels between the effects of PCP and the
symptoms of schizophrenia in the 1960s. They showed, for example, that
individuals receiving PCP exhibited the same type of disturbances in
interpreting proverbs as those with schizophrenia. More recent studies with
ketamine have produced even more compelling similarities. Notably, during
ketamine challenge, normal individuals develop difficulty thinking
abstractly, learning new information, shifting strategies or placing
information in temporary storage. They show a general motor slowing and
reduction in speech output just like that seen in schizophrenia. Individuals
given PCP or ketamine also grow withdrawn, sometimes even mute; when they
talk, they speak tangentially and concretely. PCP and ketamine rarely induce
schizophrenialike hallucinations in normal volunteers, but they exacerbate
these disturbances in those who already have schizophrenia.

One example of the research implicating NMDA receptors in schizophrenia
relates to the way the brain normally processes information. Beyond
strengthening connections between neurons, NMDA receptors amplify neural
signals, much as transistors in old-style radios boosted weak radio signals
into strong sounds. By selectively amplifying key neural signals, these
receptors help the brain respond to some messages and ignore others, thereby
facilitating mental focus and attention. Ordinarily, people respond more
intensely to sounds presented infrequently than to those presented
frequently and to sounds heard while listening than to sounds they make
themselves while speaking. But people with schizophrenia do not respond this
way, which implies that their brain circuits reliant on NMDA receptors are
out of kilter.

If reduced NMDA receptor activity prompts schizophrenia's symptoms, what
then causes this reduction? The answer remains unclear. Some reports show
that people with schizophrenia have fewer NMDA receptors, although the genes
that give rise to the receptors appear unaffected. If NMDA receptors are
intact and present in proper amounts, perhaps the problem lies with a flaw
in glutamate release or with a buildup of compounds that disrupt NMDA
activity.

Some evidence supports each of these ideas. For instance, postmortem studies
of schizophrenic patients reveal not only lower levels of glutamate but also
higher levels of two compounds (NAAG and kynurenic acid) that impair the
activity of NMDA receptors. Moreover, blood levels of the amino acid
homocysteine are elevated; homocysteine, like kynurenic acid, blocks NMDA
receptors in the brain. Overall, schizophrenia's pattern of onset and
symptoms suggests that chemicals disrupting NMDA receptors may accumulate in
sufferers' brains, although the research verdict is not yet in. Entirely
different mechanisms may end up explaining why NMDA receptor transmission
becomes attenuated.

New Schizophrenia Treatment Possibilities
Regardless of what causes NMDA signaling to go awry in schizophrenia, the
new understanding--and preliminary studies in patients--offers hope that
drug therapy can correct the problem. Support for this idea comes from
studies showing that clozapine, one of the most effective medications for
schizophrenia identified to date, can reverse the behavioral effects of PCP
in animals, something that older antipsychotics cannot do. Further,
short-term trials with agents known to stimulate NMDA receptors have
produced encouraging results. Beyond adding support to the glutamate
hypothesis, these results have enabled long-term clinical trials to begin.
If proved effective in large-scale tests, agents that activate NMDA
receptors will become the first entirely new class of medicines developed
specifically to target the negative and cognitive symptoms of schizophrenia.

The two of us have conducted some of those studies. When we and our
colleagues administered the amino acids glycine and D-serine to patients
with their standard medications, the subjects showed a 30 to 40 percent
decline in cognitive and negative symptoms and some improvement in positive
symptoms. Delivery of a medication, D-cycloserine, that is primarily used
for treating tuberculosis but happens to cross-react with the NMDA receptor,
produced similar results. Based on such findings, the National Institute of
Mental Health has organized multicenter clinical trials at four hospitals to
determine the effectiveness of D-cycloserine and glycine as therapies for
schizophrenia; results should be available this year. Trials of D-serine,
which is not yet approved for use in the U.S., are ongoing elsewhere with
encouraging preliminary results as well. These agents have also been helpful
when taken with the newest generation of atypical antipsychotics, which
raises the hope that therapy can be developed to control all three major
classes of symptoms at once.

None of the agents tested to date may have the properties needed for
commercialization; for instance, the doses required may be too high. We and
others are therefore exploring alternative avenues. Molecules that slow
glycine's removal from brain synapses--known as glycine transport
inhibitors--might enable glycine to stick around longer than usual, thereby
increasing stimulation of NMDA receptors. Agents that directly activate
"AMPA-type" glutamate receptors, which work in concert with NMDA receptors,
are also under active investigation. And agents that prevent the breakdown
of glycine or D-serine in the brain have been proposed.

Many Avenues of Attack
Scientists interested in easing schizophrenia are also looking beyond
signaling systems in the brain to other factors that might contribute to, or
protect against, the disorder. For example, investigators have applied
so-called gene chips to study brain tissue from people who have died,
simultaneously comparing the activity of tens of thousands of genes in
individuals with and without schizophrenia. So far they have determined that
many genes important to signal transmission across synapses are less active
in those with schizophrenia--but exactly what this information says about
how the disorder develops or how to treat it is unclear.

Genetic studies in schizophrenia have nonetheless yielded intriguing
findings recently. The contribution of heredity to schizophrenia has long
been controversial. If the illness were dictated solely by genetic
inheritance, the identical twin of a schizophrenic person would always be
schizophrenic as well, because the two have the same genetic makeup. In
reality, however, when one twin has schizophrenia, the identical twin has
about a 50 percent chance of also being afflicted. Moreover, only about 10
percent of first-degree family members (parents, children or siblings) share
the illness even though they have on average 50 percent of genes in common
with the affected individual. This disparity suggests that genetic
inheritance can strongly predispose people to schizophrenia but that
environmental factors can nudge susceptible individuals into illness or
perhaps shield them from it. Prenatal infections, malnutrition, birth
complications and brain injuries are all among the influences suspected of
promoting the disorder in genetically predisposed individuals.

Over the past few years, several genes have been identified that appear to
increase susceptibility to schizophrenia. Interestingly, one of these genes
codes for an enzyme (catechol-O-methyltransferase) involved in the
metabolism of dopamine, particularly in the prefrontal cortex. Genes coding
for proteins called dysbindin and neuregulin seem to affect the number of
NMDA receptors in brain. The gene for an enzyme involved in the breakdown of
D-serine (D-amino acid oxidase) may exist in multiple forms, with the most
active form producing an approximately fivefold increase in risk for
schizophrenia. Other genes may give rise to traits associated with
schizophrenia but not the disease itself. Because each gene involved in
schizophrenia produces only a small increase in risk, genetic studies must
include large numbers of subjects to detect an effect and often generate
conflicting results. On the other hand, the existence of multiple genes
predisposing for schizophrenia may help explain the variability of symptoms
across individuals, with some people perhaps showing the greatest effect in
dopamine pathways and others evincing significant involvement of other
neurotransmitter pathways.

Finally, scientists are looking for clues by imaging living brains and by
comparing brains of people who have died. In general, individuals with
schizophrenia have smaller brains than unaffected individuals of similar age
and sex. Whereas the deficits were once thought to be restricted to areas
such as the brain's frontal lobe, more recent studies have revealed similar
abnormalities in many brain regions: those with schizophrenia have abnormal
levels of brain response while performing tasks that activate not only the
frontal lobes but also other areas of the brain, such as those that control
auditory and visual processing. Perhaps the most important finding to come
out of recent research is that no one area of the brain is "responsible" for
schizophrenia. Just as normal behavior requires the concerted action of the
entire brain, the disruption of function in schizophrenia must be seen as a
breakdown in the sometimes subtle interactions both within and between
different brain regions.

Because schizophrenia's symptoms vary so greatly, many investigators believe
that multiple factors probably cause the syndrome. What physicians diagnose
as schizophrenia today may prove to be a cluster of different illnesses,
with similar and overlapping symptoms. Nevertheless, as researchers more
accurately discern the syndrome's neurological bases, they should become
increasingly skilled at developing treatments that adjust brain signaling in
the specific ways needed by each individual.

new schizophrenia drugs in development ~ steep social costs of schizophrenia

DANIEL C. JAVITT and JOSEPH T. COYLE have studied schizophrenia for many
years. Javitt is director of the Program in Cognitive Neuroscience and
Schizophrenia at the Nathan Kline Institute for Psychiatric Research in
Orangeburg, N.Y., and professor of psychiatry at the New York University
School of Medicine. His paper demonstrating that the glutamate-blocking drug
PCP reproduces the symptoms of schizophrenia was the second-most cited
schizophrenia publication of the 1990s. Coyle is Eben S. Draper Professor of
Psychiatry and Neuroscience at Harvard Medical School and also editor in
chief of the Archives of General Psychiatry. Both authors have won numerous
awards for their research. Javitt and Coyle hold independent patents for use
of NMDA modulators in the treatment of schizophrenia, and Javitt has
significant financial interests in Medifoods and Glytech, companies
attempting to develop glycine and D-serine as treatments for schizophrenia.

© 2000 HealthyPlace.com, Inc. All rights reserved.
*************************************************************

Am J Psychiatry. 2001 Sep; 158(9): 1367-77. Related Articles, Links
The emerging role of glutamate in the pathophysiology and treatment of
schizophrenia.
Goff DC, Coyle JT.   joseph_coyle@...
Schizophrenia Program, Massachusetts General Hospital, Boston, USA.

OBJECTIVE: Research has implicated dysfunction of glutamatergic
neurotransmission in the pathophysiology of schizophrenia.
This review evaluates evidence from preclinical and clinical studies that
brain glutamatergic neurotransmission is altered in schizophrenia, may
affect symptom expression, and is modulated by antipsychotic drugs.
METHOD: A comprehensive review of scientific articles published over the
last decade that address the role of glutamate in the pathophysiology of
schizophrenia was carried out.
RESULTS: Glutamatergic neurons are the major excitatory pathways linking the
cortex, limbic system, and thalamus, regions that have been implicated in
schizophrenia.
Postmortem studies have revealed alterations in pre- and postsynaptic
markers for glutamatergic neurons in several brain regions in schizophrenia.
The N-methyl-D-aspartic acid (NMDA) subtype of glutamate receptor may be
particularly important as blockade of this receptor by the dissociative
anesthetics reproduces in normal subjects the symptomatic manifestations of
schizophrenia, including negative symptoms and cognitive impairments, and
increases dopamine release in the mesolimbic system.
Agents that indirectly enhance NMDA receptor function via the glycine
modulatory site reduce negative symptoms and variably improve cognitive
functioning in schizophrenic subjects receiving typical antipsychotics.
CONCLUSIONS: Dysfunction of glutamatergic neurotransmission may play an
important role in the pathophysiology of schizophrenia, especially of the
negative symptoms and cognitive impairments associated with the disorder,
and is a promising target for drug development.
Publication Types:  Review   Review, Tutorial   PMID: 11532718


Ann N Y Acad Sci. 2003 Nov; 1003: 318-27.
Converging evidence of NMDA receptor hypofunction in the pathophysiology of
schizophrenia.   tsaig@...
Coyle JT, Tsai G, Goff D.  joseph_coyle@...

McLean Hospital, Belmont, Massachusetts 02478, USA.
Numerous clinical studies demonstrate that subanesthetic doses of
dissociative anesthetics, which are noncompetitive antagonists at the NMDA
receptor, replicate in normal subjects the cognitive impairments, negative
symptoms, and brain functional abnormalities of schizophrenia.
Postmortem and genetic studies have identified several abnormalities
associated with schizophrenia that would interfere with the activation of
the glycine modulatory site on the NMDA receptor.
Placebo-controlled clinical trials with agents that directly or indirectly
activate the glycine modulatory site consistently reduce negative symptoms
and frequently improve cognition in patients with chronic schizophrenia who
are receiving concurrent typical antipsychotics.
Thus, there is convincing evidence that hypofunction of a subset of NMDA
receptors may contribute to the symptomatic features of schizophrenia.
PMID: 14684455


Psychopharmacology (Berl). 2003 Nov 25
The NMDA receptor glycine modulatory site: a therapeutic target for
improving cognition and reducing negative symptoms in schizophrenia.
Coyle JT, Tsai G.  joseph_coyle@...
tsaig@...
Department of Psychiatry, Harvard Medical School, McLean Hospital, 02478,
Belmont, MA, USA.

Numerous clinical studies demonstrate that subanaesthetic doses of
dissociative anaesthetics, which are non-competitive antagonists at the NMDA
receptor, replicate in normal subjects the cognitive impairments, negative
symptoms and brain functional abnormalities of schizophrenia.
Post-mortem and genetic studies have identified several abnormalities
associated with schizophrenia that would interfere with the activation of
the glycine modulatory site on the NMDA receptor.
Placebo controlled clinical trials with agents that directly or indirectly
activate the glycine modulatory site consistently reduce negative symptoms
and frequently improve cognition in patients with chronic schizophrenia, who
are receiving concurrent typical antipsychotics.
Thus, there is convincing evidence that the glycine modulatory site on the
NMDA receptor is a valid therapeutic target for improving cognition and
associated negative symptoms in schizophrenia.  PMID: 14647972


Curr Drug Target CNS Neurol Disord. 2002 Apr; 1(2): 183-9.
Ionotropic glutamate receptors as therapeutic targets in schizophrenia.
Coyle JT, Tsai G, Goff DC
joseph_coyle@...  tsaig@...

Evidence implicating dysfunction of glutamatergic neurotransmission rests
largely on the finding that antagonists of the NMDA subtype of glutamate
receptor, especially the dissociative anesthetics like ketamine, can
reproduce the full range of symptoms as well as the physiologic
manifestation of schizophrenia such as hypofrontality, impaired prepulse
inhibition and enhanced subcortical dopamine release.
To test the hypothesis that schizophrenia may result from NMDA receptor
hypofunction a number of clinical trials have examined the effects of agents
that act on the glycine modulatory site on the NMDA receptor.
Glycine, D-serine, and the partial agonist, D-cycloserine, have been shown
to improve cognition and decrease negative symptoms in schizophrenic
subjects receiving typical antipsychotics.
Results with D-cycloserine suggest that clozapine may enhance glycine
modulatory site occupancy. Preliminary results with an allosteric modulator
of the AMPA subtype of glutamate receptor suggest enhanced cognitive
functions in subjects treated with clozapine.  Publication Types:  Review
Review, Tutorial   PMID: 12769626


Annu Rev Pharmacol Toxicol. 2002; 42: 165-79. Related Articles, Links
Glutamatergic mechanisms in schizophrenia.
Tsai G, Coyle JT.    joseph_coyle@...
Laboratory of Molecular and Psychiatric Neuroscience, Mailman Research
Center, Department of Psychiatry, McLean Hospital, Harvard Medical School,
Belmont, Massachusetts 02478, USA. tsaig@...

Schizophrenia is a chronic, severely disabling brain disorder with
symptomatic onset in early adulthood.
Typical antipsychotic medications that block dopamine D2 receptors are most
effective in treating the psychosis but have limited effects on the negative
symptoms and cognitive impairments.
Considerable research has demonstrated that noncompetitive NMDA receptor
antagonists, the dissociative anaesthetic like phencyclidine and ketamine,
reproduce the cardinal symptomatic features of schizophrenia.
Postmortem studies reveal variable alterations in glutamate receptors and
their modulators in schizophrenia.
Several clinical trials indicate agents that enhance NMDA receptor function
via the glycine modulatory site reduce negative and variably improve
cognitive function in schizophrenics receiving typical antipsychotics.
Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may
participate in the pathophysiology of schizophrenia.
Publication Types: Review  Review, Tutorial   PMID: 11807169
************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 749 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1057 posts in a public searchable archive  121 members

http://groups.yahoo.com/group/aspartame/messages 770 with 16,616 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
(becomes formaldehyde in body):
EU Scientific Committee on Foods 7.12.1: Murray 1.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1056
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 3.11.4

http://groups.yahoo.com/group/aspartameNM/message/1057
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/946
Functional Therapeutics in Neurodegenerative Disease Part 1/2:
Perlmutter 7.15.99: Murray 1.10.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/97
Lancet website aspartame letter 7.29.99:
Excitotoxins 1999 Part 1/3 Blaylock: Murray 1.14.0 rmforall
The Medical Sentinel Journal  1999 Fall; (95 references)
http://www.dorway.com/blayenn.html
aspartame (methanol, formaldehyde) toxicity: Murray 1.1.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1034
Brain cell damage from amino acid isolates (aspartame releases
phenylalanine, aspartate, methanol [formaldehyde, formic acid]  Bowen &
Evangelista May 6 2002: Murray 11.10.3 rmforall

http://www.aspartame.ca/Brain%20Cell%20Damage.pdf
Brain cell damage from amino acid isolates 5.6.2   41 references
detailed 22 page review by James D. Bowen, MD and Arthur M. Evangelista,
former FDA Investigator  orwilly@...

http://groups.yahoo.com/group/aspartameNM/message/628
Rich Murray: Professional House Doctors: Singer:  EPA: CPSC:
formaldehyde toxicity 6.10.1 rmforall
*************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1056
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 3.11.4

Edward J. Calabrese, 57, offers a profound insight, based on wide-ranging
evidence.  Small doses of many toxins are actually beneficial.  This complex
effect is called hormesis.

It can only benefit the health of humanity to engage in civil,
evidence-based discourse that includes many points of view.  The spectrum
from black to white includes many shades of grey, many dimensions of color.
The ongoing  evolution of truth inevitably grows beyond initial certitudes,
strongly held pros and cons, into an ever more elastic, supple appreciations
of unexpected, surprising subtleties and complexities, and higher order
unities.  Long-standing divisions and polarized conflicts unexpectedly
become cooperative networks.

Those who are willing to investigate the possiblities of positive effects
from low level aspartame (methanol, formaldehyde) exposure are led into the
joint agreement that methanol and formaldehyde toxicity are relevant to the
aspartame conundrum.   They can start to cooperate in investigating in many
ways exactly what dosages and what effects occur for different groups of
users.  The issue of aspartame toxicity can be widely acknowledged as valid,
vital, and verifiable,  subject to responsible personal, professional, and
public scrutiny and decision.

Hormesis as a Biological Hypothesis  Feb 1998 review:
"The wide range of hormetic effects (e.g., increased growth, fecundity,
longevity, and decreased disease incidence) suggests that these changes are
fundamental and affect thousands of genes. This implies that hormetic
mechanisms are likely to be operational in a very upstream location.
Nevertheless investigators often focus on mechanisms more closely related to
biological protection. For example, substantial evidence exists in numerous
species that specific alterations in patterns of gene expression occur in
response to toxicant exposure. Such responses can be sorted into two
classes: those resulting in an enhanced metabolic capacity for
detoxification (e.g., the cytochrome P450 gene family) and those that offer
a more general protection against cellular damage caused by a wide variety
of agents (e.g., heat shock or stress proteins)."

[ Crit Rev Toxicol. 2003; 33(3-4): 407-24. Related Articles, Links
Ethanol and hormesis.
Calabrese EJ, Baldwin LA.
Department of Environmental Health Sciences, Morrill Science Center,
University of Massachusetts, Amherst, MA 01003, USA.
edwardc@...

This article provides a detailed assessment of the toxicological and
pharmacological literature concerning alcohol-induced biphasic dose-response
relationships. The assessment reveals that alcohol-induced hormetic-like
dose-response relationships are commonly observed, highly generalizeable
according to model and endpoint and quantitative feature of the dose
response. These findings have important implications affecting study design,
animal model, and endpoint selection as well as clinical applications.
Publication Types: Review  Review, Tutorial  PMID: 12809430

Crit Rev Toxicol. 2003; 33(3-4): 355-405.
Peptides and hormesis.
Calabrese EJ, Baldwin LA.
Department of Environmental Health Sciences, University of Massachusetts,
Amherst, MA 01003, USA. edwardc@...

The article provides a broad assessment of the occurrence of hormetic-like
biphasic dose-response relationships by over 30 peptides representing many
major peptide classes. These peptide-induced biphasic dose responses were
observed to occur in a extensive range of tissues, affecting an diverse
range of biological endpoints. Despite diversity of peptides, models and
endpoints, the quantitative features of the biphasic dose responses are
remarkably similar with respect to the amplitude and width of the
stimulatory response. These findings strongly suggest that hormetic-like
biphasic dose responses represent a broadly generalizable biological
phenomenon.
Publication Types: Review  Review Literature  PMID: 12809429 ]

The scientific information about aspartame is clear.  It has an 11% methanol
(wood alcohol) component, which is immediately released into the GI tract,
and then made by the liver into formaldehyde and formic acid the same day.
About 30% of the methanol remains each day in all tissues as these toxic
products.

It is hardly surprising, then, that since its FDA approval in July, 1981,
there have been thousands of physician and citizen complaints about
aspartame reactions: headache, poor memory, impaired concentration,
irritability, fatigue, insomnia, aching joints and body pains, rashes,
dizziness, eye and vision problems, and even ideopathic seizures.

For the public service, I have worked tenaciously as a volunteer activist on
the world Net for five years, writing hundreds of polite, lucid, balanced,
lengthly, detailed, boring reviews of mainstream scientific research on the
issue of aspartame toxicty.

However, I admit that there are many users who operate at a high level of
competence in difficult careers, for instance, politicians, their staff, and
the media:

" http://www.mcall.com/features/all-hhtjan09.story
From The Morning Call    frank.devlin@...    610-778-2235

Mainlining Diet Coke:    Believe it or not - drinking Diet Coke makes dreams
come true.
By Frank Devlin  of  The Morning Call   January 9, 2004

Don't believe it?

Then how do you explain the way Diet Coke keeps popping up as the celebrity
soda of choice? Surely there's some link between success and this
caffeinated, chemically sweetened serum.

Take Harvey Weinstein, head of the Miramax Pictures movie studio. U.S. News
and World Report reports Weinstein has a limousine ''outfitted with video
screens and seat pockets stocked with Diet Coke.'

Or presidential candidate John Edwards, who would ''chain-drink Diet Cokes''
when he was a hotshot personal injury lawyer, according to the Charlotte
Observer, and who's drinking about 10 cans a day now on the campaign trail.

Bill Clinton, Donald Trump and Major League Baseball Commissioner Bud Selig
are also reported to be devoted Diet Coke drinkers...."

So, as truth consecrated scientists, we have to look for evidence that
formaldehyde exposure, surely disastrous at medium and high levels, may be
beneficial in some ways, at some low level for some types of people.

If such a person happens to be playing a public pro-aspartame role, then
their own personal experience will naturally make them resistant to the anti
point of view.  Perhaps, more is involved than, say, vested corporate
interests, personal larceny, and ingrained professional arrogance, in the
perpetual, tenaciously polarized debate beween the pro side and the laymen,
amateurs, complainers, mavericks, fools, nut cases, fanatics, and rumor
mongers on the anti side, who have been rudely and exasperatedly talking
past each other for two decades.

Perhaps, both sides can join in a grudging admission that the research on
the actual biochemistry of formaldehyde and formic acid in humans from
methanol is strikingly skimpy, and may even lead to proving beneficial
effects for some people at low levels for some period of time.

That's just the sort of complex outcome that often results in many such
bitter, unresolvable scientific debates.  The unstoppably exponential
advance of world toxicology renders breakthrough results impendingly
available, always far faster than expected.  My goal is to provide extensive
information and suggestive leads to speed the process of fresh examination
and exploration of the complex facts of this contested case.  Open-minded,
civil, cooperative  communication is essential for the success of science in
ameliorating human pain.

[ re Ramazzini Foundation research,  led by Morando Soffritti :
So this careful lifelong study by world class experts on total tumors in
hundreds of rats exposed almost lifelong to a wide range of formaldehyde
levels found evidence suggestive of  hormesis at the levels of 10, 50, and
100 ppm, and then the usual toxic effect of increasing lifetime total tumors
at 500, 1,000, and 1,500 ppm in drinking water.

One possible hypothesis is that the low formaldehyde levels were enough to
eliminate tumor promoting  contamination, virusus, or bacteria in the water
or even in the body tissues.  This deserves to be checked out by careful
studies.  Of course, much more complex, subtle biochemical possibilities
must exist. ]

European Ramazzini Foundation, led by Morando Soffritti, MD.
crcfr@...  Cancer Research Center, European Ramazzini Foundation for
Oncology and Environmental Sciences, Bentivoglio Castle, 40010
Bentivoglio (BO), Italy.  +39-051-6640460 fax +39-051-6640223

Annuals of the New York Academy of Science. 2002 Dec; Vol. 982.

I carefully examined the details of two long reports by Soffritti:

  p. 56  Table 2. shows for groups of 100 rats, lifetime total tumors per 100
rats increasing with high (almost lifelong ) methanol in drinking water,
except that females have have the same lifelong tumor rate at 5,000 ppm as
at 500 ppm.  Males have more tumors than females at all 3 high methanol
levels.  Low levels were not tested.

The EPA limit for methanol in human drinking water is 7.8 mg daily, or 3.9
ppm for 2 L daily.

[ "Humans, due perhaps to the loss of two enzymes during evolution, are
more sensitive to methanol than any laboratory animal; even the monkey
is not generally accepted as a suitable animal model (42)."
42.     Roe, O., Species Differences in Methanol Poisoning. CRC
Critical Rev. in Tox., pp. 275-286, October, (1982).  In:

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall

Dr. Woodrow C. Monte  Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984;  36 (1):  42-54.
(62 references)   Professsor of Food Science [retired 1992]
Arizona State University,  Tempe, Arizona 85287  woodymonte@...
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame.  The EPA limit for water is 7.8 mg daily
for methanol (wood alcohol), a deadly cumulative poison. Many users
drink 1-2 L daily. The reported symptoms are entirely consistent
with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but,
like all juices, has 16 times more ethanol, which strongly protects
against methanol.) ]

  p. 95 Table 2. shows lifetime total tumors per 100 rats for groups of 100
rats fed formaldehyde almost lifelong in drinking water, at levels 0, 500,
5,000, and 20,000 ppm.

Males
0 ppm had 50, 10 ppm had 38 (24% less),  50 ppm had 30 (40% less),
                                         100 ppm had 46 (  8% less).

Females
0 ppm had 49, 10 ppm had 44 (10 % less), 50 ppm had 52 (  6% more),
                                         100 ppm had 85 (67% more).

Males were higher than females only for 500 ppm and 1,500 ppm, in contrast
with the results for methanol.

The combined sexes at 0 ppm had  49.5, while for methanol
the combined sexes  at  0 ppm had 63.0 (27% more).  The authors do not
comment on this large control group disparity.  Both groups had 200 rats.

Comparing the methanol and formaldehyde results, we roughly estimate that in
drinking water for rats, lifelong total tumor rates are about the same,
about 100 lifetime tumors per 100 rats, for 20,000 ppm methanol and 1,500
ppm formaldehyde.

If about  3% of the aspartame remains in body tissues as formaldehyde and
formic acid products, then their similar lifetime rat studies already
carried out with aspartame might show significantly more tumors for about
45,000 ppm  in nearly lifelong drinking water, which is 45,000 mg/L.  Diet
soda has 560
mg/L aspartame, so this would be about 80 times more concentrated.

The EPA limit for formaldehyde in human drinking water is 2 mg daily, or 1
ppm for 2  L daily.   The EPA limit usually is established about a
hundred-fold less than any known toxic level.

[ http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall ]

So this careful lifelong study by world class experts on total tumors in
hundreds of rats exposed almost lifelong to a wide range of formaldehyde
levels found evidence suggestive of  hormesis at the levels of 10, 50, and
100 ppm, and then the usual toxic effect of increasing lifetime total tumors
at 500, 1,000, and 1,500 ppm in drinking water.

One possible hypothesis is that the low formaldehyde levels were enough to
eliminate tumor promoting  contamination, virusus, or bacteria in the water
or even in the body tissues.  This deserves to be checked out by careful
studies.  Of course, much more complex, subtle biochemical possibilities
must exist.

I discuss some of these with respect to aspartame, methanol, formaldehyde,
including more examples of possible hormesis,  in:

http://groups.yahoo.com/group/aspartameNM/message/1057
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall

Note also that Yu F. Sasaki found probable genotoxicity in mice from a
single aspartame dose of 2,000 mg/L [ ppm ]:

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]
*************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

p. 48 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol. (25)"
"(25) Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.
(30) Monte WC. 1984; Aspartame, methanol and the public health.
Journal Applied Nutrition. Vol 36: 42-54."

Ann N Y Acad Sci. 2002 Dec; 982: 46-69.
Results of long-term experimental studies on the carcinogenicity of
methyl alcohol and ethyl alcohol in rats.
Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Methyl alcohol was administered in drinking water supplied ad libitum at
doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female
Sprague-Dawley rats 8 weeks old at the start of the experiment.
Animals were kept under observation until spontaneous death.
Ethyl alcohol was administered by ingestion in drinking water at a
concentration of 10% or 0% supplied ad libitum to groups of male and
female Sprague-Dawley rats; breeders and offspring were included in the
experiment.
Treatment started at 39 weeks of age (breeders), 7 days before mating,
or from embryo life (offspring) and lasted until their spontaneous death.
Under tested experimental conditions, methyl alcohol and ethyl alcohol
were demonstrated to be carcinogenic for various organs and tissues.
They must also be considered multipotential carcinogenic agents.
In addition to causing other tumors, ethyl alcohol induced malignant
tumors of the oral cavity, tongue, and lips.
These sites have been shown to be target organs in man by epidemiologic
studies.  Publication Types: Review  Review, Tutorial  PMID: 12562628

[  p. 56  Table 2. shows for groups of 100 rats, lifetime total tumors per
100 rats increasing with high (almost lifelong ) methanol in drinking water,
except that females have have the same lifelong tumor rate at 5,000 ppm as
at 500 ppm.  Males have more tumors than females at all 3 high methanol
levels.  Low levels were not tested. ]

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11) [Medinsky & Dorman 1994]"

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Formaldehyde was administered for 104 weeks in drinking water supplied ad
libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L [ ppm ]
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
rats beginning at six weeks of age at concentrations of 2,500, 1,500,
500, 250, 50, or 0 mg/L. [ ppm ]
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase in total
malignant tumors in the treated groups and showed specific carcinogenic
effects on various organs and tissues.  PMID: 12562630

[  p. 95 Table 2. shows lifetime total tumors per 100 rats for groups of 100
rats fed formaldehyde almost lifelong in drinking water, at levels 0, 500,
5,000, and 20,000 ppm.

Males
0 ppm had 50, 10 ppm had 38 (24% less),  50 ppm had 30 (40% less),
                                         100 ppm had 46 (  8% less).

Females
0 ppm had 49, 10 ppm had 44 (10 % less), 50 ppm had 52 (  6% more),
                                         100 ppm had 85 (67% more).  ]


Surely the authors deliberately emphasized that aspartame is well-known
to be a source of formaldehyde, which is an extremely potent, cumulative
toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested
aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No.      No. of Bioassays  Species    No.  Route of Exposure
108. "Coca-Cola"    4      Rat    1,999   Ingestion, Transplantal Route
109. "Pepsi-Cola"    1      Rat       400   Ingestion
110.  Sucrose          1      Rat       400   Ingestion
111.  Caffeine          1      Rat       800   Ingestion
112.  Aspartame      1      Rat    1,800   Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.
*******************************************************************

In order to help those who may wish to attend to details, we summarize some
other studies on aspartame, methanol, and formaldehyde in rats.

This aspartame industry team found that in rats 50% of oral methanol or
aspartame remained in the body.  Two other teams found that 4 to 11% of
injected formaldehyde in rats is retained after 48 hours.

J Toxicol Environ Health. 1976 Nov; 2(2): 441-51.
Comparative metabolism of aspartame in experimental animals and humans.
Ranney RE, Oppermann JA, Muldoon E, McMahon FG.

Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid,
methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening
agent that organoleptically has about 180 times the sweetness of sugar.
The metabolism of aspartame has been studied in mice, rats, rabbits, dogs,
monkeys, and humans.
The compound was digested in all species in the same way as are natural
constituents of the diet.
Hydrolysis of the methyl group by intestinal esterases yielded methanol,
which was oxidized in the one-carbon metabolic pool to CO2.+
The resultant dipeptide was split at the mucosal surface by dipeptidases and
the free amino acids were absorbed.
The aspartic acid moiety was transformed in large part to CO2 through its
entry into the tricarboxylic acid cycle.
Phenylalanine was primarily incorporated into body protein either unchanged
or as its major metabolite, tyrosine.   PMID: 827618

This 1976 study by a G.D. Searle & Co. laboratory proved, using an
undisclosed number of rats, that by 8 hours, fully 50% of oral methanol or
oral aspartame was no longer being eliminated in exhaled air, as shown on
Figure 2: Cumulative 14-CO2  excretion by rats.

They did not specify any detailed numbers, or mention urine and feces,
although in 1973 in their similar study on 3 to 4 small monkeys, they gave
numbers like 73.0+- 3.1% for methanol excretion in exhaled air, 3.17+- .31%
in urine, and "little" in feces.

They did not point out that in rats this meant that fully 50% of the
methanol or aspartame must therefore accumulate daily as unspecified
products, almost certainly highly toxic formaldehyde and formic acid
products.

Two other teams found that about 4 to 11% of injected formaldehyde in rats
is retained in the body.

Life Sci 1991;48(11):1031-41
The toxicity of methanol.
Tephly TR.  [a notable pro-aspartame scientist]
Department of Pharmacology, University of Iowa, Iowa City 52242.

p. 1033 "The effects of methanol in lower animals are quite different from
those seen in humans and primates in that metabolic acidosis and ocular
toxicity are normally not seen (13).  This makes it impossible to
extrapolate results obtained from experiments using non-human animals to
humans....Monkeys are susceptible to methanol toxicity and serves as the
only model of intoxiction (14)."

p. 1036 "About 85% of a low dose of 14C-formaldehyde [radioactive label] is
excreted as pulmonary 14CO2 (49,50)....."

49. Biochem. Pharmacol. 13: 1137-1142 (1964).
The metabolic fate of formaldehyde-C14 intraperitoneally administered
to the rat.
W. Brock Neely
Biochemical Research Labs, Dow Chemical Co., Midland, Michigan

In one rat, a 60.5 mg/kg dose = 2,000 mmol/kg was injected, and by 48
hours, 82.0% was in the exhaled air as CO2 and 13.9 % was in the urine
= total 95.9% excreted, so 4 % was retained in the body.

50.  Xenobiotica 1982 Feb;12(2):119-24
Formaldehyde metabolism by the rat: a re-appraisal.
Mashford PM, Jones AR.
Dept. of Biochemistry, University of Sidney, Australia
(grant from Geistlich Sons Ltd, Pharmaceuticals, Chester, UK)

Six rats were injected with a 4 mg/kg dose = 133 mmol/kg, and by 48 hours,
82% was in the exhaled air as CO2, and 7.5% in the urine =  total
89.5% excreted, so 10.5% was retained in the body.
*******************************************************************

http://hdlighthouse.org/research/general/updates/0080toxin.phtml
the HD lighthouse: Huntington's Disease: information and community

Toxin 3NPA and Huntington's Disease

HD Lighthouse Editor's Comment: Edward J. Calabrese has over 500
publications in peer reviewed journals. He is professing radical new
treatment ideas. At least one Huntington's researcher is listening.
Calabrese's expertise on toxins may lead to treatments to delay the onset of
Huntington's disease (HD).

Sugar cane workers sometimes developed a disease that mimics HD. The cause
is the toxin 3-nitropropionic acid (3NPA) found in sugar cane mold. 3NPA is
used to make a HD mouse model. To my knowledge every agent that treats the
3NPA HD mouse also treats the genetic HD mouse.

As a striking fact genetic HD mice are resistant to 3NPA damage. What ever
the mouse does to defend against HD also defends against the toxin 3NPA. A
treatment for HD may be found in sugar cane because sugar cane probably
defends against 3NPA. Such a candidate agent has been recently found in
sugar cane (ref).

In plants, insects and humans 3NPA is a powerful mitochondrial toxin. 3NPA
has been found in peanuts and corn. 3NPA is produced by some plants as a
defense against insects or competing plants. Finding out how plants defend
against 3NPA could bring treatments for HD. As an environmental toxin 3NPA
is not measured by the Environmental Protection Agency. We may all be
exposed to low doses of 3NPA.
The following suggests that low doses of 3NPA may increase defences against
HD to delay onset. Some good science has to be done before any human dare
take 3NPA. --Jerry    Posted to the HDL: 12 Dec 2003

A New Idea For Treatment

HD researcher Mark Mattson recently invited Calabrese to visit his lab to
discuss the possibility of experiments that would test whether low doses of
otherwise toxic chemicals strengthen the brain's defenses against diseases
like Alzheimer's, Parkinson's, or Huntington's.

A scientist finds benefit in small doses of toxins
By Gareth Cook, Globe Staff, 12/12/2003

AMHERST -- Edward J. Calabrese, a gray-haired man who works in a rundown
office surrounded by documents on highly toxic chemicals, has an explosive
idea.

For more than a decade, Calabrese, a respected professor of toxicology at
the University of Massachusetts, endured ridicule as he gathered evidence
showing that small amounts of poisons, even cancer-causing chemicals like
dioxin, can be good for you.

His research threatens to overturn a key principle of environmental
regulation, which assumes that if a large quantity of a chemical causes
cancer, then a small quantity is still dangerous, and that the ideal amount
is zero. Calabrese's work suggests that for many chemicals, exposure to a
low level may be healthier than no exposure at all.

Though long relegated to the scientific fringe, Calabrese's idea is suddenly
being taken seriously. He has landed several papers in prestigious research
journals. Other scientists are citing his work, the invitations to speak at
universities and scientific meetings are flooding in, and the concept has
been added to two leading toxicology textbooks.

All of this has put Calabrese at the center of a politically charged debate
with broad implications for health. If the regulations that protect the
nation's air, water, and soil are not stringent enough to keep toxins below
hazardous levels, Americans will die. Yet if Calabrese is correct, and small
quantities of many toxins can actually be beneficial, then it could bring
innovative drug therapies, save billions by relaxing overly strict
environmental standards, and fundamentally change the way scientists and the
public think about poisons.

"I think he is shaking us all up in a way that is really useful," said
George Gray, a toxicologist who is executive director of the Harvard Center
for Risk Analysis.

The concept underlying Calabrese's work is called "hormesis." In the broad
sense it is hardly controversial. Vitamins are healthy in the right dose;
toxic in larger ones. A glass of red wine a day can be good for you; a
gallon is not. But this is not how scientists have traditionally thought
about the risks posed by environmental chemicals. One of toxicology's most
important tools is to observe the effects of large doses of a chemical on
laboratory animals, and then use that data to estimate the effects of much
lower doses on humans over longer periods.

In the case of cancer-causing agents, toxicologists assume that the harmful
effects decrease as the dosage goes down, but that they do not hit zero
until the exposure is zero. For threats not involving cancer, the model is
only slightly different; scientists also assume that smaller doses cause
less harm, and the harmful effects hit zero as soon as the dose hits a
certain low threshold.

These two ideas form the bedrock of modern toxicology, but Calabrese began
to suspect that they were wrong when he discovered, as a college student,
that spraying peppermint plants with very low doses of a growth retardant
made the plants grow larger. So at low doses, the growth inhibitor didn't
just stop working -- it had the opposite of its intended effect.

Other scientists have noticed unexpected effects like this, Calabrese said.
At low doses, both dioxin and DDT have been shown to reduce some cancers in
lab animals. Low doses of cadmium, which can be highly toxic, reduces liver
cancer in rats.

In his research, Calabrese, 57, has shown that these effects may be very
common.

Calabrese and a colleague searched through the toxicology literature,
looking for all examples where scientists had measured the response to doses
below the threshold at which the chemical is thought to have no effect.
Their statistical analysis, published this year in the journal Toxicological
Sciences, showed that, on average, these low doses had a measurable
effect -- itself a surprise -- and that the effect was the opposite of the
large-dose effect. Chemicals that had a bad effect at high doses tended to
have a beneficial one at small doses.

Their analysis included a wide variety of life forms -- including plants,
animals, and microbes -- and of effects -- such as growth, reproduction, and
behavior.

"What I think is going on here is a revolution in thought to a bunch of
people who are not used to a revolution," Calabrese said.

Before hormesis could be used to justify changes in regulations, scientists
would need a better understanding for exactly how it works, said William H.
Farland, acting deputy assistant administrator for science in the Office of
Research and Development at the Environmental Protection Agency. A chemical
that is beneficial in one way may cause problems in other areas, he said. Or
levels of a chemical that may be healthy for some people, or even positive,
may be harmful for children, pregnant women, or others.

And even when unexpected things happen at small doses, they are not always
positive. Several researchers have found that certain chemicals that act
like hormones can cause damage at much lower levels than anyone had
expected.

As the science improves, Farland said, researchers are seeing more and more
surprises at low levels of exposure.

This "most likely represents very complex biology," Farland said, "and what
we have to do now is understand that biology."

One mechanism behind hormesis is that small amounts of chemicals can evoke a
stress response from cells, causing them to devote resources to defending
themselves.

For example, laboratory animals forced to fast periodically, and thereby put
stress on their entire system, develop neurons that are more resistant to
diseases like Parkinson's, according to research done by Mark P. Mattson,
chief of the Laboratory of Neuroscience at the National Institute on Aging.
Other experiments have shown that chemicals can evoke the same stress
responses.

Mattson recently invited Calabrese to visit his lab to discuss the
possibility of experiments that would test whether low doses of otherwise
toxic chemicals strengthen the brain's defenses against diseases like
Alzheimer's, Parkinson's, or Huntington's.

"The idea would be to identify a treatment that could be given long term and
delay the onset of disease," Mattson said. "This is a long way from
something that could be applied in humans, but it is worth pursuing.

Calabrese's work, said Farland and other scientists, is part of a dramatic
rethinking of the biological effects of low-level exposures. New scientific
tools and the explosion of detailed genetic information is allowing
scientists to move from the standard animal toxicity tests, which use
massive doses, to a more detailed looks at how individual molecules interact
with living cells. This has led to a growing recognition that effects can
differ in kind, not just degree, as the concentration changes.

Indeed, the National Toxicology Program, the government's clearinghouse for
toxicology research, just began an expansive, year-long review to change its
approach, given the developing scientific approaches.

"The idea is, what are we going to do to change this discipline," said
Christopher J. Portier, the program's associate director. "I am sure that
hormesis will be a part of the discussion as we move through this."
# # #
Trached on the HDL: Mark Matson
Edward Calabrese
Source: Adopted from:The Boston Globe 12 Dec 2003
*******************************************************************

Huntington's Disease And Calorie Restriction
... HD Lighthouse Editor's Comment: Mark Matson, researcher at the National
Institute of Health, found that lowering calories forestalls Huntington's
disease in
...
hdlighthouse.org/treatment-care/care/hdltriad/
diet/updates/0062sirtuins.phtml - 22k -

Not Skipping Meals May Damage Brain
... Edition the week of April 28, 2003 . All about professor Mark P. Matson.
# # #. Source: NIH/National Institute on Aging, 28 Apr 2003 ...
hdlighthouse.org/treatment-care/care/hdltriad/diet/updates/0053skipmeal.phtm
l - 20k -

Toxin 3NPA and Huntington's Disease
... I am sure that hormesis will be a part of the discussion as we move
through this." # # #. Trached on the HDL: Mark Matson.

Edward Calabrese. ...
hdlighthouse.org/research/general/ updates/0080toxin.phtml - 22k

New Drugs Protect Nerve Cells In Parkinson Mice
... Would these mice develop cancer tumors or HD symptoms? The new drugs
being investigated by researcher Matson are P53 suppressors. ...
hdlighthouse.org/research/general/ updates/0056p53.shtml - 19k
********************************************************************

http://www.sciam.com/article.cfm?articleID=00019A70-0C1C-1F41-B0B980A841890000

In Depth     August 18, 2003   HORMESIS

Nietzsche's Toxicology; Whatever doesn't kill you might make you stronger
By Rebecca Renner

Image: RALPH WHITE Corbis

POLLUTION STANDARDS that factories--such as this chemical plant on Lake
Baikal, Russia--must meet may change if hormesis proves to be a
widespread phenomenon.

If dioxin and ionizing radiation cause cancer, then it stands to reason that
less exposure to them should improve public health. If mercury, lead and
PCBs impair intellectual development, then less should be more. But a
growing body of data suggests that environmental contaminants may not always
be poisonous--they may actually be good for you at low levels.

Called hormesis, this phenomenon appears to be primarily an adaptive
response to stress, says toxicologist Edward J. Calabrese of the University
of Massachusetts at Amherst. The stress triggers cellular repair and
maintenance systems. A modest amount of overcompensation then produces the
low-dose effect, which is often beneficial.

This idea may sound bizarre, but such adaptation to stress is common, says
physiologist Suresh Rattan of Århus University in Denmark. Exercise, for
instance, plays biochemical havoc with the body: starving some cells of
oxygen and glucose, flooding others with oxidants, and depressing immune
functions. "At first glance, there is nothing good for the body about
exercise," he notes. But even couch potatoes know that moderate exercise is
worthwhile. Rattan says that the cellular insults from exercise prompt the
defense system to work more efficiently.

Over the past decade, Calabrese has compiled thousands of examples of
hormesis from published scientific literature. Many findings challenge and
even flout established theories about what is harmful. For example, the
prevailing theory is that any increase in radiation exposure increases the
risk of cancer. But biologist Ronald Mitchel of Atomic Energy of Canada has
shown that a single low dose of ionizing radiation stimulates DNA repair,
delaying the onset of cancer in mice; high doses produced the opposite
effect, as expected. Prolonged exposure to extreme temperatures is also
harmful, but Rattan has found that heating up human skin cells to 41 degrees
Celsius (106 degrees Fahrenheit) twice a week for an hour slows aging in the
cells.

Even well-established environmental headaches display some hormesis. The
definitive rat study that linked high doses of dioxin to cancer, published
in 1978 by Richard Kociba of Dow Chemical and his colleagues, also found
that low doses reduced the incidence of tumors.

Image: LUCY READING; ADAPTED FROM J. R. MAISIN ET AL. IN RADIATION RESEARCH,
FEBRUARY 1988 (top) AND
TETSUYA ABE ET AL. IN BIOCHEMICAL PHARMACOLOGY, JULY
1, 1999 (bottom), AS REPRODUCED BY EDWARD J. CALABRESE AND LINDA A. BALDWIN
IN TRENDS IN PHARMACOLOGICAL SCIENCES, JUNE 2001

A PINCH OF POISON seems beneficial in some cases when compared with control
groups, as shown by the effects of gamma rays on the emergence of
mouse tumors (top) and of cadmium exposure on human ovarian cells (bottom).

"Adaptation to such stresses is absolutely essential," Mitchel remarks. "If
we couldn't adapt to changes in our environment, we would die." Such
adaptation at the molecular level is seen in most primitive forms of life
and has been evolutionarily conserved all the way up to humans, he adds.

Hormesis challenges the existing hazard-assessment process underlying
environmental regulations, Calabrese says. Toxicologists usually determine
the relation between exposure to contaminants and health risks by conducting
animal experiments. They start out by giving lab animals a high dose that
produces clear adverse effects. Then they work downward until they can
estimate a concentration that doesn't cause harmful effects. For chemicals
that don't cause cancer, they obtain a safe dose for humans by applying
uncertainty factors to account for differences between mice and men and
among individual people. The resulting safe dose for humans is then usually
deemed to be about 0.01 to 0.001 the safe dose for mice. For carcinogens,
toxicologists assume that exposure to any amount increases the risk.

But Calabrese suspects that in many cases, the benefits of hormesis may
occur at levels higher than the recommended safe doses for humans. Thus, it
might be possible to refine pollution standards so that we can reap the
benefits of hormesis while still being protected against adverse effects in
the environment. Or at the very least, it might be reasonable to stop
worrying about exceedingly low exposures.

Researchers investigating adaptive stress responses aren't the only ones
interested in effects at low doses. Scientists studying endocrine disruption
are also joining in. They are concerned that contaminants that mimic
hormones can have significant harmful effects at very low doses if exposure
occurs during a susceptible developmental window. In some sense, endocrine
disruption appears to be the opposite of hormesis, in which low doses could
have unsuspected harmful effects because of the contaminant's chemical
similarity to hormones.

Advances in molecular biology are giving toxicologists the tools to
investigate low-dose phenomena, according to Joseph V. Rodricks, health
sciences director at Environ, environmental consultants in Arlington, Va.
Instead of monitoring the onset of disease or cancer, toxicologists are
beginning to use modern molecular biology tools to identify the critical
early precursors to illness. They then monitor how the precursors vary at
low doses.

Hormesis has much to prove if it is to revolutionize toxicology, Rodricks
notes. Many of the hormetic dose-response relations that Calabrese has
compiled raise more questions than answers, he says. For example, the dioxin
study looks like hormesis if all types of cancer are combined, but hormesis
doesn't show for individual types of cancer. Despite such skepticism,
Rodricks is one of many toxicologists calling for a National Research
Council review of this phenomenon.

Rebecca Renner writes about environmental issues from Williamsport, Pa.
*******************************************************************

Harihara M. Mehendale mehendale@...;
A. R. B. Stebbing tony.stebbing@...;
Elaina M. Kenyon kenyon.elaina@...;
davis.jmichael@...;
J. Michael Davis Davis.Jmichael@...;
Joseph V. Rodricks < jrodricks@...>;
Ronald Mitchel mitchelr@...;
Suresh I. Rattan rattan@...;
William H. Farland farland.william@... ;
George Gray ggray@...;
Christopher J. Portier christopher.portier@...;
Mark P. Mattson mark.mattson@...;
Edward J. Calabrese edwardc@...;
Thomas J. Goehl <goehl@...>;
Rebecca Renner <applepie@...>;
Linda A. Baldwin <baldwinl@...>;
M. A. Medinsky" <toxcon@...>;
D.C. Dorman dorman@...
*******************************************************************

Toxicological Defense Mechanisms and the Shape of Dose-Response
Relationships
Environmental Health Perspectives 106, Supplement 1, February 1998
Hormesis as a Biological Hypothesis
Edward J. Calabrese and Linda A. Baldwin
Department of Environmental Health Sciences, School of Public Health,
University of Massachusetts, Amherst, Massachusetts

Abstract
A comprehensive effort was undertaken to identify articles demonstrating
chemical hormesis.
Nearly 4000 potentially relevant articles were retrieved from preliminary
computer database searches by using various key word descriptors and
extensive cross-referencing.
A priori evaluation criteria were established including study design
features (e.g., number of doses, dose range), statistical analysis, and
reproducibility of results.
Evidence of chemical hormesis was judged to have occurred in approximately
350 of the 4000 studies evaluated.
Chemical hormesis was observed in a wide range of taxonomic groups and
involved agents representing highly diverse chemical classes, many of
potential environmental relevance.
Numerous biological end points were assessed; growth responses were the
most prevalent, followed by metabolic effects, longevity, reproductive
responses, and survival.
Hormetic responses were generally observed to be of limited magnitude.
The average low-dose maximum stimulation was approximately 50% greater
than controls.
The hormetic dose-response range was generally limited to about one order of
magnitude, with the upper end of the hormetic curve approaching the
estimated no observable effect level for the particular end point.
Based on the evaluation criteria, high to moderate evidence of hormesis was
observed in studies comprised of>6 doses; with>3 doses in the hormetic zone.
The present analysis suggests that chemical hormesis is a reproducible and
relatively common biological phenomenon.
A quantitative scheme is presented for future application to the
database. -- Environ Health Perspect 106(Suppl 1):357-362 (1998).
http://ehpnet1.niehs.nih.gov/docs/1998/Suppl-1/357-362calabrese/abstract.html
Key words: hormesis, [beta]-curve, stimulation, low dose, U-shaped

This paper is based on a presentation at The Third BELLE Conference on
Toxicological Defense Mechanisms and the Shape of Dose-Response
Relationships held 12-14 November 1996 in Research Triangle Park, NC.
Manuscript received at EHP 29 April 1997; accepted 17 July 1997.
This report was sponsored in part by an award to the University of
Massachusetts (E.J. Calabrese, Principal Investigator) by the Texas
Institute for Advancement of Chemical Technology, Inc.
Address correspondence to Dr. E.J. Calabrese, Department of Environmental
Health Sciences, School of Public Health, University of Massachusetts,
Amherst, MA 01003. Telephone: (413) 545-3164. Fax: (413) 545-4692.
E-mail: edwardc@...
Abbreviations used: LOEL, lowest observable effect level; NOEL, no
observable effect level.
[Table of Contents] [Full Article] [Citation in PubMed] [Related Articles]
Last Update: March 11, 1998

Introduction
The concept of chemical hormesis has a long history, originating over a
century ago from the research of Schulz (1), who noted that many chemicals
were able to stimulate growth and respiration of yeast at low doses but were
inhibitory at higher levels. This concept of a generalized low-dose
stimulation-high-dose inhibition was gradually supported by similar
observations with other chemicals and eventually became known as the
Arndt-Schulz law. Although Schulz (1) ushered in the so-called modern
concept of hormesis, Paracelsus (2), writing in the 16th century, likewise
noted that various toxic substances may be beneficial in small quantities.

Despite the widespread recognition of apparent hormetic effects, which
continued into the early decades of the 20th century, Stebbing (2) argues
that the Arndt-Schulz law gradually fell into disuse because it did not
provide an adequate explanatory (i.e., mechanism-based) capacity.
Nonetheless, over the years a continuing stream of observations has been
reported (2) in toxicological publications and the broader biological
literature that document low-dose stimulations.

Although there has been long-standing interest in the concept of chemical
hormesis few attempts have been made to summarize the extent of its
occurrence in biological systems and its potential to generalize with
respect to animal models, biological end points, or chemical class. Previous
limited summaries have been reported (2-6). In addition, Davis and
Svendsgaard (7) attempted to assess the statistical likelihood of low-dose
stimulation among a random sample of experimental studies published in
prominent toxicological journals. The goal of this research was to extend
the findings of these previous reports by attempting to evaluate in a
comprehensive manner those studies that are believed or alleged to display
evidence of chemical hormesis. These findings would then be employed to
assess the scientific basis of the hypothesis that hormesis is induced by
chemical agents and is a generalized biological phenomenon.

Criteria for Evaluating Hormesis
To conduct this investigation it was necessary to define chemical hormesis
and develop a priori criteria to evaluate its possible occurrence in
experimental or empirical investigations. The definition derived from
Stebbing (2) is low-dose stimulation followed by higher-dose inhibition; the
most common form of hormesis follows the widely recognized ß-curve (Figure
1). The use of the ß-curve follows principally from the widespread use of
growth as a principal end point in hormesis research. However, the term U
shaped, as emphasized by Davis and Svendsgaard (8), would most
appropriately be applied when the end point relates to a traditional
toxicologically based health end point such as cancer incidence.  The
criteria applied in the present methodology were the same for the ß-curve
and U-shaped relationships.

Figure 1. The most common dose-response curve showing hormesis--the ß-curve.

Because hormesis is a scientific hypothesis the question of whether it is
beneficial is often contextual. To eliminate subjective decisions concerning
beneficial versus harmful effects, the decision was made to evaluate model-
and end point-specific responses with respect to stimulation and inhibition.
For example, stimulation of detoxifying enzyme levels observed in the larval
form of a species would be evaluated for its hormetic potential even though
this increased metabolic activity, although beneficial in the short-term,
may have a detrimental effect on other end points. Likewise the stimulation
of microbial reproduction by antibiotics was evaluated for its hormetic
potential even though these low dose effects are harmful to the host
organism.

This assessment of chemical hormesis has been restricted to those
dose-response relationships most conforming to the ß-curve and would be
affected by the magnitude of the low-dose stimulatory response, the number
of doses establishing the reliability of the ß-curve, the presence of
statistical analysis, and the reproducibility of the findings. Within this
category only the well-known types of dose-response relationships exhibiting
ß- or U-shaped curves (represented by nutritionally essential substances,
with the exception of copper) were excluded, as this phenomenon is generally
accepted.

The capacity to evaluate high conformity to the ß-curve ideally requires the
establishment of an end point-specific lowest observable effect level (LOEL)
and no observable effect level (NOEL), with multiple doses within two orders
of magnitude immediately below the NOEL. This suggests that to be a relevant
study for the evaluation of chemical hormesis, an experiment would be
expected to have four or more doses distributed in a highly specific manner
relative to the NOEL. Therefore, highly restrictive study design
requirements must be satisfied to adequately assess chemical hormesis. Most
toxicological studies do not satisfy these design criteria and would be
classified as nonrelevant, as they are unable to demonstrate no evidence or
some evidence (i.e., equal to or greater than low evidence) of hormesis.
Similarly, data from epidemiological studies, with the exception of reports
on ethanol and cardiovascular disease, were difficult to conform to these
criteria. Within this evaluative context judgment on the evidence supporting
consistency of data from an individual experiment with the definition of
chemical hormesis was made by a weight-of-evidence procedure. It should be
noted that upward-curving ß- or U-shaped dose-response curves (e.g.,
characteristic of certain studies where low doses reduce mortality) were
included in the analysis. In addition many studies contain multiple
dose-response relationships for the same or different end points. In these
cases all end points within a study showing low-dose stimulation were
evaluated.

To facilitate an appreciation of weight-of-evidence evaluation methodology,
several graphic examples are presented that illustrate how such judgments
concerning chemical hormesis may be made (Figure 2A-E).

Figure 2. Dose-response curves illustrating various data sets evaluated for
chemical hormesis.
Figure 2A depicts a hypothetical study with a dose range of 10-fold that
displays a modest statistically insignificant increase (i.e., stimulation)
in response at the lowest dose followed by a more definitive decrease (i.e.,
inhibition). Using the criteria applied in the present methodology this
study would be judged as a) displaying an extremely limited dosage range
probably inadequate for assessment of the dynamics of the dose-response
continuum, b) inadequately describing the dose-response relationship in the
hypothetical hormetic zone, and c) having inadequate statistical power to
conclude that the stimulatory effort was treatment related. An initial
screen of such an experiment would most likely result in a designation of
not highly relevant to assess the hormesis hypothesis. However, the study
would be retained for further evaluation within a weight-of-evidence
context, based on the observation of the low-dose stimulation. At present
this experiment would be most consistent with either a low or not relevant
evidence designation of hormesis. Neither categorical placement is
convincing.

Figure 2B likewise depicts a study with a limited dose range (10-fold) with
a limited number of doses. However in contrast to Figure 2A, a more striking
stimulatory response is seen at the lowest dose, which is highly
statistically significant. However, this study is limited by having only one
dose showing a stimulatory response even though the response was impressive.
A case can be made for either a low or moderate evidence classification of
hormesis.

Figure 2C depicts a study with a markedly larger dose range (500-fold) and
number of doses (seven), with three doses in the hypothetical hormetic zone
(i.e., doses less than the NOEL). However, the magnitude of stimulation is
very limited and the observed increases are not statistically significant.
This experiment would probably be considered as no or low evidence of
hormesis. It would of course be a relevant study because of the wide dosage
range, the substantial number of doses, the inclusion of doses below the
LOEL, and the observation, although inconclusive, of stimulation at low
dose.
Figure 2D depicts a study with a very broad dose range (>1000-fold) and a
large number of doses (11), with a low-dose stimulatory response observed in
seven doses in the hypothetical hormetic zone. In addition the results
display considerable statistical power. This type of study would receive a
high evidence ranking.

Figure 2E depicts a study with a wide range of doses (>500) and a large
number of concentrations with adequate statistical power. However the data
do not show any evidence of a low-dose stimulation. This study would receive
a not relevant designation because it does not establish a NOEL nor does it
have any doses below the NOEL.

Nature and Yield of Search Strategy
Table 1 summarizes the search strategy and yield. Computerized library
searches were conducted on BIOSIS (Knight-Ridder Information, Mountain
View, CA; 1969-1996), Chemical Abstracts (Knight-Ridder Information;
1967-1996), and Medline (Knight-Ridder Information; 1966-1996) using
hormesis and the combination of U shaped plus dose response as key word
descriptors. One
hundred fifty-two publications were retrieved using hormesis as the key word
descriptor; 165 publications were retrieved using the combination of U
shaped plus dose response. Radiation hormesis was the subject of 104 of the
317 publications.

Based on information obtained from the initial searches described above,
additional search strategies were employed using the same three databases
and the following key word descriptors: low dose plus stimulation, beta
curve plus dose response, adaptation plus pollution, and homeopathy. A total
of 4058 articles was identified then reduced to 3272 following elimination
of database replication of articles. Manual review of the 3272 abstracts
revealed approximately 172 potentially relevant publications, the majority
of which were chemically oriented. Radiation studies comprised approximately
25% of the 172 articles.

A computerized library search conducted on the database Agricola
(Knight-Ridder Information; 1970-September 1995) using the key word
descriptors hormesis, U shaped plus dose response, and low dose plus
stimulation revealed very few articles not already identified in the
previous searches.

To include the most recent articles, computerized searches of the Current
Contents Life Sciences and Agricultural, Biological, and Environmental
Sciences databases (Institute for Scientific Information, Philadelphia, PA)
for the time period 15 May 1995 through 5 June 1996 were conducted using
the key word descriptors hormesis, U shaped plus dose response, low dose
plus stimulation, adaptation plus pollution, and beta curve.

Only a small number of new articles not included in the prior searches was
identified.
Potentially relevant articles not included in the computerized library
searches were obtained from extensive cross-referencing of primary sources.

Most recently additional search strategies were employed using BIOSIS,
Medline, and Chemical Abstracts and the following key word descriptors:
doses plus sublethal, doses plus subtoxic, doses plus subthreshold,
responses plus sublethal, responses plus subtoxic, and responses plus
subthreshold. A total of 5569 articles was identified then reduced to 3776
following elimination of database replication of articles. Manual review of
the 3776 abstracts revealed approximately 67 potentially relevant
publications.

A computerized library search using the same key word descriptors listed
above and the database Agricola (1970-September 1996) identified 230
articles. When reviewed approximately 25 were considered potentially
relevant. The same key word descriptors were also used in computerized
searches of the Current Contents Life Sciences and Agricultural, Biological,
and Environmental Sciences databases for the time period 16 October 1995
through 7 October 1996 to include the most recent articles. Of the 214
abstracts identified, 27 new articles were considered potentially relevant.
Finally, computer searches of Science Citations (Institute for Scientific
Infor-mation; 1990-1996) were conducted using authors' names Stebbing ARD
and Luckey TD. Approximately 400 articles were identified, of which 149 were
considered potentially relevant.

Results of Article Evaluation
Those studies placed within a high evidence category of chemical hormesis
had the greatest number of total study doses (i.e., 6.3 on average) and
doses in the so-called hormetic zone (i.e., 3.4 on average), followed by
studies demonstrating moderate evidence and more distantly by studies
demonstrating low evidence (Table 2).

The types of chemicals that induce hormetic effects represent a broad range
of chemical classes (Table 3). The most studied agents were metals, followed
by alcohols, antibiotics, auxin-related compounds, and numerous biocidal
agents. The range of hormetic responses is listed in Table 4 and indicates
that the principal end point is growth, followed by metabolic changes (e.g.,
enzyme activity), longevity, and various reproductive indices.

Characteristics of the Chemical Hormetic Zone
To assess the characteristics of the chemical hormetic dose-response zone,
experimental data were evaluated with respect to a) the dosage range of the
hormetic zone (i.e., from the estimated dosage where the response starts to
deviate from the control to the estimated dosage where the response begins
to dip below the controls); b) the maximum stimulatory response (as a
percentage greater than the control response); and c) the magnitude of
dosage difference from the maximum stimulatory response and the estimated
NOEL (Figure 3).

Figure 3. Dose-response curve depicting characteristics of the chemical
hormetic zone. ZEP, zero equivalent point.

In general the hormetic dose-response range is usually within a 10-fold
range. Stimulatory effects, however, have been reported over dosage ranges
of two or more orders of magnitude as well as over a more narrow range of
dosages depending on the agent, end point, and model assessed. The magnitude
of stimulatory responses has been observed as high as several-fold but the
majority of low-dose stimulations are 30 to 60% greater than the controls.
The distance from the maximum stimulatory response to the NOEL is difficult
to discern as it is a function of the number of doses employed, their
variability in response, and the estimated value of the NOEL. Nonetheless,
the distance between the maximum stimulatory response and the estimated
NOEL is typically observed in the 3- to 6-fold range (i.e., the NOEL is
about 3- to 6-fold greater than the maximum stimulatory response).

Hormesis as a General Biological Phenomenon
Hormetic responses are observed in numerous species from a broad range of
taxonomic groups including microbes, plants, and animals (Table 5). These
responses occur with a large number of chemicals representing a broad range
of chemical classes (Table 3). Although Stebbing (2) focused principally on
growth hormesis, the present report indicates that hormetic effects are
observed in a broad range of biological end points that involve not only
growth but survival, longevity, reproduction, and numerous metabolic and
physiological responses (e.g., metallothionein synthesis, DNA synthesis, RNA
synthesis, mitosis, oxygen consumption, altered hepatic foci, photosynthesis
rate, tissue regeneration, immune response, stress protein synthesis,
germination of seeds, etc.). Thus hormesis appears relatively common with
respect to species, chemical, and biological end point.

The ability to generalize hormetic responses also extends to the descriptive
nature of the dose-response phenomenon itself. As Stebbing (2) noted
earlier, when the data are precise and comprehensive, the points appear to
fit a ß-curve and have remarkable similarity with respect to the range and
amplitude of response. However it should be emphasized that the
developmental dynamics of the hormetic dose response over time have not been
widely or systematically studied. For example, while Stebbing (2) found that
the form of the curve varied during the course of the experiment with hydra,
Calabrese and Howe (9) observed a consistent shape of the ß-curve over 4 to
6 weeks in plant growth experiments.

Why is Hormesis Infrequently Observed?
If hormesis is believed to be relatively common, questions arise as to why
it is not reported more frequently and why the Arndt-Schulz law failed to
become established. The infrequent reports of hormesis are most likely
attributable to a combination of factors, predominantly the issue of
appropriate study design, along with the influence on safety evaluation,
which emphasizes the upper end of the dose-response continuum (i.e., where
higher concentrations establish toxic responses that can be used in chemical
evaluation and risk assessment). The present conclusions support this
assessment; a direct relationship has been shown between the strength of the
evidence supporting hormesis and the number of doses, including both overall
experimental number of doses and the number of doses in the hormetic zone.
Furthermore, because the average range of the hormetic zone is about one
order of magnitude this phenomenon is difficult to discern when wide dose
intervals (e.g., >10-fold) are used.

Predictive insight into the number of published articles potentially
displaying hormesis may be derived as follows. Assuming 500,000 toxicology
studies have been published this century (based on searches of Chemical
Abstracts, Index Medicus, and BIOSIS), it is estimated that approximately
350,000 toxicology articles have been published since 1966. Thus we assume
for the sake of argument that 500,000 toxicology papers comprise the
available pool for evaluation. If we also assume that 2% of these studies
include six or more doses (10) then 10,000 studies may contain dose ranges
adequate for hormesis evaluation. Of these 10,000 studies, based on the
characteristics defining hormetic studies, approximately 10% (i.e., 1000)
have three or more doses below the estimated NOEL. Further refinement of
this estimation can be made by assuming that 90% of these 1000 studies have
doses in the low-dose range within one to two orders of magnitude and close
to the estimated NOEL (10).

These figures suggest that mammalian toxicologists may have had only limited
direct interaction with the concept of hormesis, as only an estimated 900
potentially relevant studies exist. Therefore it is not surprising that
toxicologists may view hormesis more as a belief than a phenomenon and that
the Arndt-Schulz law (i.e., hormesis) fell into general disuse.

In addition to the low number of hormetic observations reported, Stebbing
(2) suggested that the Arndt-Schulz Law fell into disuse because it lacked
an explicit mechanism component. However, the concept of adaptation, a
potentially important explanatory component for hormesis, has evolved for
the most part independent of hormesis. Although numerous studies of
adaptation exist, only a limited number address specific mechanisms
applicable to chemically induced hormetic dose-response relationships.
Nonetheless there are studies that have sought to mechanistically explain
specific hormetic dose-response relationships.

Perhaps the most systematically assessed mechanism-based research has been
in the area of herbicide-induced stimulatory effects. Hormetic responses
have long been recognized by herbicide researchers who have conducted
studies assessing not only the molecular basis for the response but also the
effect of the plant species and age on the response.

A growing number of mammalian examples also exists where plausible
explanatory mechanisms have been put forth to account for specific hormetic
dose-response relationships (11-15).

The wide range of hormetic effects (e.g., increased growth, fecundity,
longevity, and decreased disease incidence) suggests that these changes are
fundamental and affect thousands of genes. This implies that hormetic
mechanisms are likely to be operational in a very upstream location.
Nevertheless investigators often focus on mechanisms more closely related to
biological protection. For example, substantial evidence exists in numerous
species that specific alterations in patterns of gene expression occur in
response to toxicant exposure. Such responses can be sorted into two
classes: those resulting in an enhanced metabolic capacity for
detoxification (e.g., the cytochrome P450 gene family) and those that offer
a more general protection against cellular damage caused by a wide variety
of agents (e.g., heat shock or stress proteins).

Proposed Quantitative Evaluation Scheme
A quantitative scheme has been developed to provide a more objective and
reproducible methodology for ranking studies with respect to hormetic
potential. Criteria have been established and assigned point values based
on: the number of experimental doses below the NOEL, experimental
determination or estimation of the high NOEL, the statistical significance
of the stimulatory response, the magnitude (percentage of control value) of
the stimulatory response, and the reproducibility of data by other studies
(Tables 6 and 7). Evidence of hormesis will be assessed by comparing the
summation of point values to point ranges established for six evidence
categories: high, moderate-high, moderate, low-moderate, low, and no-low
(Table 8). Results of the application of this methodology and comparison
with the current qualitative findings will be published elsewhere (16).

Summary
A goal of the present research is to create a database of studies
demonstrating objective evidence of hormesis. It is hoped that this
database, when complete, will enable the scientific community to evaluate
more rigorously and efficiently the concept of hormesis with respect to its
status as a biological hypothesis, its potential to be generalized, and its
impact on environmental and human health.

The findings to date indicate that examples of low-dose stimulation
consistent with ß-curve characteristics are copious, diverse, independently
derived, and reproducible. Yet despite the large number of such observations
no long-term systematic effort has been made to uncover explanatory
mechanisms, except in limited cases (e.g., herbicidal agents).

A more objective and reproducible evaluation methodology for ranking studies
with respect to hormetic potential is needed. The development of
quantitative criteria based on study design, response, and reproducibility
of findings is proposed and will be applied to the current database.

Furthermore, statistical simulations of dose-response relationships given
various types of variability in control groups can provide important insight
into the establishment of more quantifiable criteria in the evaluation of
possible hormetic findings. The area of hormesis and its evaluation as a
biological hypothesis has striking similarities to the evolving mathematical
area of meta-analysis in epidemiology. In fact the application of
meta-analysis techniques to the evaluation of hormetic response data is
likely to yield significant advances.

References
1. Schulz H. Ueber Hefegifte. Pfluegers Arch Gesamte Physiol Menschen Tiere
42: 517 (1888).

2. Stebbing ARD. Hormesis--the stimulation of growth by low levels of
inhibitors. Sci Total Environ 22: 213-234 (1982).

3. Townsend JF, Luckey TD. Hormoligosis in pharmacology. J Am Med Assoc
173: 44-48 (1960).

4. Luckey TD. Hormology with inorganic compounds. In: Heavy Metal Toxicity,
Safety, and Hormology, Supplement Volume 1 (Coulston F, Korte F, eds).
Stuttgart:George Thieme, 1975; 83-118.

5. Calabrese EJ, McCarthy M, Kenyon E. The occurrence of chemical
hormesis. Health Phys 57: 531-54 (1987).

6. Calabrese EJ. Primer on BELLE. In: Biological Effects of Low Level
Exposures: Dose-Response Relationships (Calabrese EJ, ed). Boca Raton,
FL:CRC/Lewis Publishers, 1994; 27-42.

7. Davis JM, Svendsgaard DJ. Nonmonotonic dose-response relationships in
toxicological studies. In: Biological Effects of Low Level Exposures:
Dose-Response Relationships (Calabrese EJ, ed). Boca Raton, FL:CRC/Lewis
Publishers, 1994; 67-86.

8. Davis JM, Svendsgaard DJ. U-shaped dose-response curves: their
occurrence and implications for risk assessment. J Toxicol Environ Health
30: 71-83 (1990).

9. Calabrese EJ, Howe KJ. Stimulation of growth of peppermint (Mentha
piperita) by phosfon, a growth retardant. Physiol Plant 37: 163-165 (1976).

10. Calabrese EJ. Unpublished data.

11. Calabrese EJ, Baldwin LA, Mehendale HM. Contemporary issues in
toxicology: G2 subpopulation in rat liver induced into mitosis by low level
exposure to carbon tetrachloride: an adaptive response. Toxicol Appl
Pharmacol 121: 1-7 (1993).

12. Calabrese EJ, Mehendale HM. A review of the role of tissue repair as an
adaptive strategy: why low doses are often non-toxic and why high doses can
be fatal. Food Chem Toxicol 34: 301-311 (1996).

13. Hart RW, Frame LT. Toxicological defense mechanisms and how they may
affect the nature of dose-response relationships. BELLE Newslett 5: 1-16
(1996).

14. Mukherjee SN, Rawal SK, Ghumare SS, Sharma RN. Hormetic
concentrations of azadirachtin and isoesterase profiles in Tribolium
castraneum (Herbst) (Coleoptera:Tenebrionidae). Experientia 49: 557-560
(1993).

15. Vichi P, Tritton TR. Stimulation of growth in human and murine cells by
adriamycin. Cancer Res 49:  2679-2682 (1989).

16. Calabrese EJ, Baldwin LA. Quantitatively-based methodology for the
evaluation of chemical hormesis. Hum Ecol Risk Assess 4: 545-554 (1997).
*******************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.aspartame
(methanol, formaldehyde) toxicity: Murray 1.24.4 rmforall

http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1057 posts in a public searchable archive  125 members

http://groups.yahoo.com/group/aspartame/messages 759 with 16,425 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L (becomes
formaldehyde in body):
EU Scientific Committee on Foods 7.12.1: Murray 1.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1037
Joe Trippi, heavy user of Diet Pepsi (aspartame toxicity), Dean's campaign
manager: Murray 11.16.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/927
Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall
********************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1055
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 1.27.4

Edward J. Calabrese, 57, offers a profound insight, based on wide-ranging
evidence.  Small doses of many toxins are actually beneficial.  This complex
effect is called hormesis:

Hormesis as a Biological Hypothesis  Feb 1998 review:
"The wide range of hormetic effects (e.g., increased growth, fecundity,
longevity, and decreased disease incidence) suggests that these changes are
fundamental and affect thousands of genes. This implies that hormetic
mechanisms are likely to be operational in a very upstream location.
Nevertheless investigators often focus on mechanisms more closely related to
biological protection. For example, substantial evidence exists in numerous
species that specific alterations in patterns of gene expression occur in
response to toxicant exposure. Such responses can be sorted into two
classes: those resulting in an enhanced metabolic capacity for
detoxification (e.g., the cytochrome P450 gene family) and those that offer
a more general protection against cellular damage caused by a wide variety
of agents (e.g., heat shock or stress proteins)."

[ Crit Rev Toxicol. 2003; 33(3-4): 407-24. Related Articles, Links
Ethanol and hormesis.
Calabrese EJ, Baldwin LA.
Department of Environmental Health Sciences, Morrill Science Center,
University of Massachusetts, Amherst, MA 01003, USA.
edwardc@...

This article provides a detailed assessment of the toxicological and
pharmacological literature concerning alcohol-induced biphasic dose-response
relationships. The assessment reveals that alcohol-induced hormetic-like
dose-response relationships are commonly observed, highly generalizeable
according to model and endpoint and quantitative feature of the dose
response. These findings have important implications affecting study design,
animal model, and endpoint selection as well as clinical applications.
Publication Types: Review  Review, Tutorial  PMID: 12809430

Crit Rev Toxicol. 2003; 33(3-4): 355-405.
Peptides and hormesis.
Calabrese EJ, Baldwin LA.
Department of Environmental Health Sciences, University of Massachusetts,
Amherst, MA 01003, USA. edwardc@...

The article provides a broad assessment of the occurrence of hormetic-like
biphasic dose-response relationships by over 30 peptides representing many
major peptide classes. These peptide-induced biphasic dose responses were
observed to occur in a extensive range of tissues, affecting an diverse
range of biological endpoints. Despite diversity of peptides, models and
endpoints, the quantitative features of the biphasic dose responses are
remarkably similar with respect to the amplitude and width of the
stimulatory response. These findings strongly suggest that hormetic-like
biphasic dose responses represent a broadly generalizable biological
phenomenon.
Publication Types: Review  Review Literature  PMID: 12809429 ]

The scientific information about aspartame is clear.  It has an 11% methanol
(wood alcohol) component, which is immediately released into the GI tract,
and then made by the liver into formaldehyde and formic acid the same day.
About 30% of the methanol remains each day in all tissues as these toxic
products.

It is hardly surprising, then, that since its FDA approval in July, 1981,
there have been thousands of physician and citizen complaints about
aspartame reactions: headache, poor memory, impaired concentration,
irritability, fatigue, insomnia, aching joints and body pains, rashes,
dizziness, eye and vision problems, and even ideopathic seizures.

For the public service, I have worked tenaciously as a volunteer activist on
the world Net for five years, writing hundreds of polite, lucid, balanced,
lengthly, detailed, boring reviews of mainstream scientific research on the
issue of aspartame toxicty.

However, I admit that there are many users who operate at a high level of
competence in difficult careers, for instance, politicians, their staff, and
the media:

" http://www.mcall.com/features/all-hhtjan09.story
From The Morning Call    frank.devlin@...    610-778-2235

Mainlining Diet Coke:    Believe it or not - drinking Diet Coke makes dreams
come true.
By Frank Devlin  of  The Morning Call   January 9, 2004

Don't believe it?

Then how do you explain the way Diet Coke keeps popping up as the celebrity
soda of choice? Surely there's some link between success and this
caffeinated, chemically sweetened serum.

Take Harvey Weinstein, head of the Miramax Pictures movie studio. U.S. News
and World Report reports Weinstein has a limousine ''outfitted with video
screens and seat pockets stocked with Diet Coke.'

Or presidential candidate John Edwards, who would ''chain-drink Diet Cokes''
when he was a hotshot personal injury lawyer, according to the Charlotte
Observer, and who's drinking about 10 cans a day now on the campaign trail.

Bill Clinton, Donald Trump and Major League Baseball Commissioner Bud Selig
are also reported to be devoted Diet Coke drinkers...."

So, as truth consecrated scientists, we have to look for evidence that
formaldehyde exposure, surely disastrous at medium and high levels, may be
beneficial in some ways, at some low level for some types of people.

If such a person happens to be playing a public pro-aspartame role, then
their own personal experience will naturally make them resistant to the anti
point of view.  Perhaps, more is involved than, say, vested corporate
interests, personal larceny, and ingrained professional arrogance, in the
perpetual, tenaciously polarized debate beween the pro side and the laymen,
amateurs, complainers, mavericks, fools, nut cases, fanatics, and rumor
mongers on the anti side, who have been rudely and exasperatedly talking
past each other for two decades.

Perhaps, both sides can join in a grudging admission that the research on
the actual biochemistry of formaldehyde and formic acid in humans from
methanol is strikingly skimpy, and may even lead to proving beneficial
effects for some people at low levels for some period of time.

That's just the sort of complex outcome that often results in many such
bitter, unresolvable scientific debates.  The unstoppably exponential
advance of world toxicology renders breakthrough results impendingly
available, always far faster than expected.  My goal is to provide extensive
information and suggestive leads to speed the process of fresh examination
and exploration of the complex facts of this contested case.  Open-minded,
civil, cooperative  communication is essential for the success of science in
ameliorating human pain.

[ re Ramazzini Foundation research,  led by Morando Soffritti :
So this careful lifelong study by world class experts on total tumors in
hundreds of rats exposed almost lifelong to a wide range of formaldehyde
levels found evidence suggestive of  hormesis at the levels of 10, 50, and
100 ppm, and then the usual toxic effect of increasing lifetime total tumors
at 500, 1,000, and 1,500 ppm in drinking water.

One possible hypothesis is that the low formaldehyde levels were enough to
eliminate tumor promoting  contamination, virusus, or bacteria in the water
or even in the body tissues.  This deserves to be checked out by careful
studies.  Of course, much more complex, subtle biochemical possibilities
must exist. ]

European Ramazzini Foundation, led by Morando Soffritti, MD.
crcfr@...  Cancer Research Center, European Ramazzini Foundation for
Oncology and Environmental Sciences, Bentivoglio Castle, 40010
Bentivoglio (BO), Italy.  +39-051-6640460 fax +39-051-6640223

Annuals of the New York Academy of Science. 2002 Dec; Vol. 982.

I carefully examined the details of two long reports by Soffritti:

  p. 56  Table 2. shows for groups of 100 rats, lifetime total tumors per 100
rats increasing with high (almost lifelong ) methanol in drinking water,
except that females have have the same lifelong tumor rate at 5,000 ppm as
at 500 ppm.  Males have more tumors than females at all 3 high methanol
levels.  Low levels were not tested.

The EPA limit for methanol in human drinking water is 7.8 mg daily, or 3.9
ppm for 2 L daily.

[ "Humans, due perhaps to the loss of two enzymes during evolution, are
more sensitive to methanol than any laboratory animal; even the monkey
is not generally accepted as a suitable animal model (42)."
42.     Roe, O., Species Differences in Methanol Poisoning. CRC
Critical Rev. in Tox., pp. 275-286, October, (1982).  In:

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall

Dr. Woodrow C. Monte  Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984;  36 (1):  42-54.
(62 references)   Professsor of Food Science [retired 1992]
Arizona State University,  Tempe, Arizona 85287  woodymonte@...
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame.  The EPA limit for water is 7.8 mg daily
for methanol (wood alcohol), a deadly cumulative poison. Many users
drink 1-2 L daily. The reported symptoms are entirely consistent
with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but,
like all juices, has 16 times more ethanol, which strongly protects
against methanol.) ]

  p. 95 Table 2. shows lifetime total tumors per 100 rats for groups of 100
rats fed formaldehyde almost lifelong in drinking water, at levels 0, 500,
5,000, and 20,000 ppm.

Males
0 ppm had 50, 10 ppm had 38 (24% less),  50 ppm had 30 (40% less).
Females
0 ppm had 49, 10 ppm had 44 (10 % less), 50 ppm had 52 (  6% more).
Males
                                         100 ppm had 46 (  8% less)
Females
                                         100 ppm had 85 (67% more)

Males were higher than females only for 500 ppm and 1,500 ppm, in contrast
with the results for methanol.

The combined sexes at 0 ppm had  49.5, while for methanol
the combined sexes  at  0 ppm had 63.0 (27% more).  The authors do not
comment on this large control group disparity.  Both groups had 200 rats.

Comparing the methanol and formaldehyde results, we roughly estimate that in
drinking water for rats, lifelong total tumor rates are about the same,
about 100 lifetime tumors per 100 rats, for 20,000 ppm methanol and 1,500
ppm formaldehyde.

If about  3% of the aspartame remains in body tissues as formaldehyde and
formic acid products, then their similar lifetime rat studies already
carried out with
aspartame might show significantly more tumors for about 45,000 ppm  in
nearly lifelong drinking water, which is 45,000 mg/L.  Diet soda has 560
mg/L aspartame, so this would be about 80 times more concentrated.

The EPA limit for formaldehyde in human drinking water is 2 mg daily, or 1
ppm for 2  L daily.   The EPA limit usually is established about a
hundred-fold less than any known toxic level.

[ http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall ]

So this careful lifelong study by world class experts on total tumors in
hundreds of rats exposed almost lifelong to a wide range of formaldehyde
levels found evidence suggestive of  hormesis at the levels of 10, 50, and
100 ppm, and then the usual toxic effect of increasing lifetime total tumors
at 500, 1,000, and 1,500 ppm in drinking water.

One possible hypothesis is that the low formaldehyde levels were enough to
eliminate tumor promoting  contamination, virusus, or bacteria in the water
or even in the body tissues.  This deserves to be checked out by careful
studies.  Of course, much more complex, subtle biochemical possibilities
must exist.

I discuss some of these with respect to aspartame, methanol, formaldehyde,
including more examples of possible hormesis,  in:

http://groups.yahoo.com/group/aspartameNM/message/1056
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 1.28.4 rmforall

Note also that Yu F. Sasaki found probable genotoxicity in mice from a
single
aspartame dose of 2,000 mg/L [ ppm ]:

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]
*************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

p. 48 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol. (25)"
"(25) Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.
(30) Monte WC. 1984; Aspartame, methanol and the public health.
Journal Applied Nutrition. Vol 36: 42-54."

Ann N Y Acad Sci. 2002 Dec; 982: 46-69.
Results of long-term experimental studies on the carcinogenicity of
methyl alcohol and ethyl alcohol in rats.
Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Methyl alcohol was administered in drinking water supplied ad libitum at
doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female
Sprague-Dawley rats 8 weeks old at the start of the experiment.
Animals were kept under observation until spontaneous death.
Ethyl alcohol was administered by ingestion in drinking water at a
concentration of 10% or 0% supplied ad libitum to groups of male and
female Sprague-Dawley rats; breeders and offspring were included in the
experiment.
Treatment started at 39 weeks of age (breeders), 7 days before mating,
or from embryo life (offspring) and lasted until their spontaneous
death.
Under tested experimental conditions, methyl alcohol and ethyl alcohol
were demonstrated to be carcinogenic for various organs and tissues.
They must also be considered multipotential carcinogenic agents.
In addition to causing other tumors, ethyl alcohol induced malignant
tumors of the oral cavity, tongue, and lips.
These sites have been shown to be target organs in man by epidemiologic
studies.  Publication Types: Review  Review, Tutorial  PMID: 12562628

[  p. 56  Table 2. shows for groups of 100 rats, lifetime total tumors per
100 rats increasing with high (almost lifelong ) methanol in drinking water,
except that females have have the same lifelong tumor rate at 5,000 ppm as
at 500 ppm.  Males have more tumors than females at all 3 high methanol
levels.  Low levels were not tested. ]

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11) [Medinsky & Dorman 1994]"

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Formaldehyde was administered for 104 weeks in drinking water supplied ad
libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L [ ppm ]
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
rats beginning at six weeks of age at concentrations of 2,500, 1,500,
500, 250, 50, or 0 mg/L. [ ppm ]
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase in total
malignant tumors in the treated groups and showed specific carcinogenic
effects on various organs and tissues.  PMID: 12562630

[  p. 95 Table 2. shows lifetime total tumors per 100 rats for groups of 100
rats fed formaldehyde almost lifelong in drinking water, at levels 0, 500,
5,000, and 20,000 ppm.

Males
0 ppm had 50, 10 ppm had 38 (24% less),  50 ppm had 30 (40% less).
Females
0 ppm had 49, 10 ppm had 44 (10 % less), 50 ppm had 52 (  6% more).
Males
                                         100 ppm had 46 (  8% less)
Females
                                        100  ppm had 85 (67% more)  ]

Surely the authors deliberately emphasized that aspartame is well-known
to be a source of formaldehyde, which is an extremely potent, cumulative
toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested
aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No.      No. of Bioassays  Species    No.  Route of Exposure
108. "Coca-Cola"    4      Rat    1,999   Ingestion, Transplantal Route
109. "Pepsi-Cola"    1      Rat       400   Ingestion
110.  Sucrose          1      Rat       400   Ingestion
111.  Caffeine          1      Rat       800   Ingestion
112.  Aspartame      1      Rat    1,800   Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.
*******************************************************************

In order to help those who may wish to attend to details, we summarize some
other studies on aspartame, methanol, and formaldehyde in rats.

This aspartame industry team found that in rats 50% of oral methanol or
aspartame remained in the body.  Two other teams found that 4 to 11% of
injected formaldehyde in rats is retained after 48 hours.

J Toxicol Environ Health. 1976 Nov; 2(2): 441-51.
Comparative metabolism of aspartame in experimental animals and humans.
Ranney RE, Oppermann JA, Muldoon E, McMahon FG.

Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid,
methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening
agent that organoleptically has about 180 times the sweetness of sugar.
The metabolism of aspartame has been studied in mice, rats, rabbits, dogs,
monkeys, and humans.
The compound was digested in all species in the same way as are natural
constituents of the diet.
Hydrolysis of the methyl group by intestinal esterases yielded methanol,
which was oxidized in the one-carbon metabolic pool to CO2.+
The resultant dipeptide was split at the mucosal surface by dipeptidases and
the free amino acids were absorbed.
The aspartic acid moiety was transformed in large part to CO2 through its
entry into the tricarboxylic acid cycle.
Phenylalanine was primarily incorporated into body protein either unchanged
or as its major metabolite, tyrosine.   PMID: 827618

This 1976 study by a G.D. Searle & Co. laboratory proved, using an
undisclosed number of rats, that by 8 hours, fully 50% of oral methanol or
oral aspartame was no longer being eliminated in exhaled air, as shown on
Figure 2: Cumulative 14-CO2  excretion by rats.

They did not specify any detailed numbers, or mention urine and feces,
although in 1973 in their similar study on 3 to 4 small monkeys, they gave
numbers like 73.0+- 3.1% for methanol excretion in exhaled air, 3.17+- .31%
in urine, and "little" in feces.

They did not point out that in rats this meant that fully 50% of the
methanol or aspartame must therefore accumulate daily as unspecified
products, almost certainly highly toxic formaldehyde and formic acid
products.

Two other teams found that about 4 to 11% of injected formaldehyde in rats
is retained in the body.

Life Sci 1991;48(11):1031-41
The toxicity of methanol.
Tephly TR.  [a notable pro-aspartame scientist]
Department of Pharmacology, University of Iowa, Iowa City 52242.

p. 1033 "The effects of methanol in lower animals are quite different from
those seen in humans and primates in that metabolic acidosis and ocular
toxicity are normally not seen (13).  This makes it impossible to
extrapolate results obtained from experiments using non-human animals to
humans....Monkeys are susceptible to methanol toxicity and serves as the
only model of intoxiction (14)."

p. 1036 "About 85% of a low dose of 14C-formaldehyde [radioactive label] is
excreted as pulmonary 14CO2 (49,50)....."

49. Biochem. Pharmacol. 13: 1137-1142 (1964).
The metabolic fate of formaldehyde-C14 intraperitoneally administered
to the rat.
W. Brock Neely
Biochemical Research Labs, Dow Chemical Co., Midland, Michigan

In one rat, a 60.5 mg/kg dose = 2,000 mmol/kg was injected, and by 48
hours, 82.0% was in the exhaled air as CO2 and 13.9 % was in the urine
= total 95.9% excreted, so 4 % was retained in the body.

50.  Xenobiotica 1982 Feb;12(2):119-24
Formaldehyde metabolism by the rat: a re-appraisal.
Mashford PM, Jones AR.
Dept. of Biochemistry, University of Sidney, Australia
(grant from Geistlich Sons Ltd, Pharmaceuticals, Chester, UK)

Six rats were injected with a 4 mg/kg dose = 133 mmol/kg, and by 48 hours,
82% was in the exhaled air as CO2, and 7.5% in the urine =  total
89.5% excreted, so 10.5% was retained in the body.
*******************************************************************

http://hdlighthouse.org/research/general/updates/0080toxin.phtml
the HD lighthouse: Huntington's Disease: information and community

Toxin 3NPA and Huntington's Disease

HD Lighthouse Editor's Comment: Edward J. Calabrese has over 500
publications in peer reviewed journals. He is professing radical new
treatment ideas. At least one Huntington's researcher is listening.
Calabrese's expertise on toxins may lead to treatments to delay the onset of
Huntington's disease (HD).

Sugar cane workers sometimes developed a disease that mimics HD. The cause
is the toxin 3-nitropropionic acid (3NPA) found in sugar cane mold. 3NPA is
used to make a HD mouse model. To my knowledge every agent that treats the
3NPA HD mouse also treats the genetic HD mouse.

As a striking fact genetic HD mice are resistant to 3NPA damage. What ever
the mouse does to defend against HD also defends against the toxin 3NPA. A
treatment for HD may be found in sugar cane because sugar cane probably
defends against 3NPA. Such a candidate agent has been recently found in
sugar cane (ref).

In plants, insects and humans 3NPA is a powerful mitochondrial toxin. 3NPA
has been found in peanuts and corn. 3NPA is produced by some plants as a
defense against insects or competing plants. Finding out how plants defend
against 3NPA could bring treatments for HD. As an environmental toxin 3NPA
is not measured by the Environmental Protection Agency. We may all be
exposed to low doses of 3NPA.
The following suggests that low doses of 3NPA may increase defences against
HD to delay onset. Some good science has to be done before any human dare
take 3NPA. --Jerry    Posted to the HDL: 12 Dec 2003

A New Idea For Treatment

HD researcher Mark Mattson recently invited Calabrese to visit his lab to
discuss the possibility of experiments that would test whether low doses of
otherwise toxic chemicals strengthen the brain's defenses against diseases
like Alzheimer's, Parkinson's, or Huntington's.

A scientist finds benefit in small doses of toxins
By Gareth Cook, Globe Staff, 12/12/2003

AMHERST -- Edward J. Calabrese, a gray-haired man who works in a rundown
office surrounded by documents on highly toxic chemicals, has an explosive
idea.

For more than a decade, Calabrese, a respected professor of toxicology at
the University of Massachusetts, endured ridicule as he gathered evidence
showing that small amounts of poisons, even cancer-causing chemicals like
dioxin, can be good for you.

His research threatens to overturn a key principle of environmental
regulation, which assumes that if a large quantity of a chemical causes
cancer, then a small quantity is still dangerous, and that the ideal amount
is zero. Calabrese's work suggests that for many chemicals, exposure to a
low level may be healthier than no exposure at all.

Though long relegated to the scientific fringe, Calabrese's idea is suddenly
being taken seriously. He has landed several papers in prestigious research
journals. Other scientists are citing his work, the invitations to speak at
universities and scientific meetings are flooding in, and the concept has
been added to two leading toxicology textbooks.

All of this has put Calabrese at the center of a politically charged debate
with broad implications for health. If the regulations that protect the
nation's air, water, and soil are not stringent enough to keep toxins below
hazardous levels, Americans will die. Yet if Calabrese is correct, and small
quantities of many toxins can actually be beneficial, then it could bring
innovative drug therapies, save billions by relaxing overly strict
environmental standards, and fundamentally change the way scientists and the
public think about poisons.

"I think he is shaking us all up in a way that is really useful," said
George Gray, a toxicologist who is executive director of the Harvard Center
for Risk Analysis.

The concept underlying Calabrese's work is called "hormesis." In the broad
sense it is hardly controversial. Vitamins are healthy in the right dose;
toxic in larger ones. A glass of red wine a day can be good for you; a
gallon is not. But this is not how scientists have traditionally thought
about the risks posed by environmental chemicals. One of toxicology's most
important tools is to observe the effects of large doses of a chemical on
laboratory animals, and then use that data to estimate the effects of much
lower doses on humans over longer periods.

In the case of cancer-causing agents, toxicologists assume that the harmful
effects decrease as the dosage goes down, but that they do not hit zero
until the exposure is zero. For threats not involving cancer, the model is
only slightly different; scientists also assume that smaller doses cause
less harm, and the harmful effects hit zero as soon as the dose hits a
certain low threshold.

These two ideas form the bedrock of modern toxicology, but Calabrese began
to suspect that they were wrong when he discovered, as a college student,
that spraying peppermint plants with very low doses of a growth retardant
made the plants grow larger. So at low doses, the growth inhibitor didn't
just stop working -- it had the opposite of its intended effect.

Other scientists have noticed unexpected effects like this, Calabrese said.
At low doses, both dioxin and DDT have been shown to reduce some cancers in
lab animals. Low doses of cadmium, which can be highly toxic, reduces liver
cancer in rats.

In his research, Calabrese, 57, has shown that these effects may be very
common.

Calabrese and a colleague searched through the toxicology literature,
looking for all examples where scientists had measured the response to doses
below the threshold at which the chemical is thought to have no effect.
Their statistical analysis, published this year in the journal Toxicological
Sciences, showed that, on average, these low doses had a measurable
effect -- itself a surprise -- and that the effect was the opposite of the
large-dose effect. Chemicals that had a bad effect at high doses tended to
have a beneficial one at small doses.

Their analysis included a wide variety of life forms -- including plants,
animals, and microbes -- and of effects -- such as growth, reproduction, and
behavior.

"What I think is going on here is a revolution in thought to a bunch of
people who are not used to a revolution," Calabrese said.

Before hormesis could be used to justify changes in regulations, scientists
would need a better understanding for exactly how it works, said William H.
Farland, acting deputy assistant administrator for science in the Office of
Research and Development at the Environmental Protection Agency. A chemical
that is beneficial in one way may cause problems in other areas, he said. Or
levels of a chemical that may be healthy for some people, or even positive,
may be harmful for children, pregnant women, or others.

And even when unexpected things happen at small doses, they are not always
positive. Several researchers have found that certain chemicals that act
like hormones can cause damage at much lower levels than anyone had
expected.

As the science improves, Farland said, researchers are seeing more and more
surprises at low levels of exposure.

This "most likely represents very complex biology," Farland said, "and what
we have to do now is understand that biology."

One mechanism behind hormesis is that small amounts of chemicals can evoke a
stress response from cells, causing them to devote resources to defending
themselves.

For example, laboratory animals forced to fast periodically, and thereby put
stress on their entire system, develop neurons that are more resistant to
diseases like Parkinson's, according to research done by Mark P. Mattson,
chief of the Laboratory of Neuroscience at the National Institute on Aging.
Other experiments have shown that chemicals can evoke the same stress
responses.

Mattson recently invited Calabrese to visit his lab to discuss the
possibility of experiments that would test whether low doses of otherwise
toxic chemicals strengthen the brain's defenses against diseases like
Alzheimer's, Parkinson's, or Huntington's.

"The idea would be to identify a treatment that could be given long term and
delay the onset of disease," Mattson said. "This is a long way from
something that could be applied in humans, but it is worth pursuing.

Calabrese's work, said Farland and other scientists, is part of a dramatic
rethinking of the biological effects of low-level exposures. New scientific
tools and the explosion of detailed genetic information is allowing
scientists to move from the standard animal toxicity tests, which use
massive doses, to a more detailed looks at how individual molecules interact
with living cells. This has led to a growing recognition that effects can
differ in kind, not just degree, as the concentration changes.

Indeed, the National Toxicology Program, the government's clearinghouse for
toxicology research, just began an expansive, year-long review to change its
approach, given the developing scientific approaches.

"The idea is, what are we going to do to change this discipline," said
Christopher J. Portier, the program's associate director. "I am sure that
hormesis will be a part of the discussion as we move through this."
# # #
Trached on the HDL: Mark Matson
Edward Calabrese
Source: Adopted from:The Boston Globe 12 Dec 2003
*******************************************************************

Huntington's Disease And Calorie Restriction
... HD Lighthouse Editor's Comment: Mark Matson, researcher at the National
Institute of Health, found that lowering calories forestalls Huntington's
disease in
...
hdlighthouse.org/treatment-care/care/hdltriad/
diet/updates/0062sirtuins.phtml - 22k -

Not Skipping Meals May Damage Brain
... Edition the week of April 28, 2003 . All about professor Mark P. Matson.
# # #. Source: NIH/National Institute on Aging, 28 Apr 2003 ...
hdlighthouse.org/treatment-care/care/hdltriad/diet/updates/0053skipmeal.phtm
l - 20k -

Toxin 3NPA and Huntington's Disease
... I am sure that hormesis will be a part of the discussion as we move
through this." # # #. Trached on the HDL: Mark Matson.

Edward Calabrese. ...
hdlighthouse.org/research/general/ updates/0080toxin.phtml - 22k

New Drugs Protect Nerve Cells In Parkinson Mice
... Would these mice develop cancer tumors or HD symptoms? The new drugs
being investigated by researcher Matson are P53 suppressors. ...
hdlighthouse.org/research/general/ updates/0056p53.shtml - 19k
********************************************************************

http://www.sciam.com/article.cfm?articleID=00019A70-0C1C-1F41-B0B980A841890000

In Depth     August 18, 2003   HORMESIS

Nietzsche's Toxicology; Whatever doesn't kill you might make you stronger
By Rebecca Renner

Image: RALPH WHITE Corbis

POLLUTION STANDARDS that factories--such as this chemical plant on Lake
Baikal, Russia--must meet may change if hormesis proves to be a
widespread phenomenon.

If dioxin and ionizing radiation cause cancer, then it stands to reason that
less exposure to them should improve public health. If mercury, lead and
PCBs impair intellectual development, then less should be more. But a
growing body of data suggests that environmental contaminants may not always
be poisonous--they may actually be good for you at low levels.

Called hormesis, this phenomenon appears to be primarily an adaptive
response to stress, says toxicologist Edward J. Calabrese of the University
of Massachusetts at Amherst. The stress triggers cellular repair and
maintenance systems. A modest amount of overcompensation then produces the
low-dose effect, which is often beneficial.

This idea may sound bizarre, but such adaptation to stress is common, says
physiologist Suresh Rattan of Århus University in Denmark. Exercise, for
instance, plays biochemical havoc with the body: starving some cells of
oxygen and glucose, flooding others with oxidants, and depressing immune
functions. "At first glance, there is nothing good for the body about
exercise," he notes. But even couch potatoes know that moderate exercise is
worthwhile. Rattan says that the cellular insults from exercise prompt the
defense system to work more efficiently.

Over the past decade, Calabrese has compiled thousands of examples of
hormesis from published scientific literature. Many findings challenge and
even flout established theories about what is harmful. For example, the
prevailing theory is that any increase in radiation exposure increases the
risk of cancer. But biologist Ronald Mitchel of Atomic Energy of Canada has
shown that a single low dose of ionizing radiation stimulates DNA repair,
delaying the onset of cancer in mice; high doses produced the opposite
effect, as expected. Prolonged exposure to extreme temperatures is also
harmful, but Rattan has found that heating up human skin cells to 41 degrees
Celsius (106 degrees Fahrenheit) twice a week for an hour slows aging in the
cells.

Even well-established environmental headaches display some hormesis. The
definitive rat study that linked high doses of dioxin to cancer, published
in 1978 by Richard Kociba of Dow Chemical and his colleagues, also found
that low doses reduced the incidence of tumors.

Image: LUCY READING; ADAPTED FROM J. R. MAISIN ET AL. IN RADIATION RESEARCH,
FEBRUARY 1988 (top) AND
TETSUYA ABE ET AL. IN BIOCHEMICAL PHARMACOLOGY, JULY
1, 1999 (bottom), AS REPRODUCED BY EDWARD J. CALABRESE AND LINDA A. BALDWIN
IN TRENDS IN PHARMACOLOGICAL SCIENCES, JUNE 2001

A PINCH OF POISON seems beneficial in some cases when compared with control
groups, as shown by the effects of gamma rays on the emergence of
mouse tumors (top) and of cadmium exposure on human ovarian cells (bottom).

"Adaptation to such stresses is absolutely essential," Mitchel remarks. "If
we couldn't adapt to changes in our environment, we would die." Such
adaptation at the molecular level is seen in most primitive forms of life
and has been evolutionarily conserved all the way up to humans, he adds.

Hormesis challenges the existing hazard-assessment process underlying
environmental regulations, Calabrese says. Toxicologists usually determine
the relation between exposure to contaminants and health risks by conducting
animal experiments. They start out by giving lab animals a high dose that
produces clear adverse effects. Then they work downward until they can
estimate a concentration that doesn't cause harmful effects. For chemicals
that don't cause cancer, they obtain a safe dose for humans by applying
uncertainty factors to account for differences between mice and men and
among individual people. The resulting safe dose for humans is then usually
deemed to be about 0.01 to 0.001 the safe dose for mice. For carcinogens,
toxicologists assume that exposure to any amount increases the risk.

But Calabrese suspects that in many cases, the benefits of hormesis may
occur at levels higher than the recommended safe doses for humans. Thus, it
might be possible to refine pollution standards so that we can reap the
benefits of hormesis while still being protected against adverse effects in
the environment. Or at the very least, it might be reasonable to stop
worrying about exceedingly low exposures.

Researchers investigating adaptive stress responses aren't the only ones
interested in effects at low doses. Scientists studying endocrine disruption
are also joining in. They are concerned that contaminants that mimic
hormones can have significant harmful effects at very low doses if exposure
occurs during a susceptible developmental window. In some sense, endocrine
disruption appears to be the opposite of hormesis, in which low doses could
have unsuspected harmful effects because of the contaminant's chemical
similarity to hormones.

Advances in molecular biology are giving toxicologists the tools to
investigate low-dose phenomena, according to Joseph V. Rodricks, health
sciences director at Environ, environmental consultants in Arlington, Va.
Instead of monitoring the onset of disease or cancer, toxicologists are
beginning to use modern molecular biology tools to identify the critical
early precursors to illness. They then monitor how the precursors vary at
low doses.

Hormesis has much to prove if it is to revolutionize toxicology, Rodricks
notes. Many of the hormetic dose-response relations that Calabrese has
compiled raise more questions than answers, he says. For example, the dioxin
study looks like hormesis if all types of cancer are combined, but hormesis
doesn't show for individual types of cancer. Despite such skepticism,
Rodricks is one of many toxicologists calling for a National Research
Council review of this phenomenon.

Rebecca Renner writes about environmental issues from Williamsport, Pa.
*******************************************************************

Harihara M. Mehendale mehendale@...;
A. R. B. Stebbing tony.stebbing@...;
Elaina M. Kenyon kenyon.elaina@...;
davis.jmichael@...;
J. Michael Davis Davis.Jmichael@...;
Joseph V. Rodricks < jrodricks@...>;
Ronald Mitchel mitchelr@...;
Suresh I. Rattan rattan@...;
William H. Farland farland.william@... ;
George Gray ggray@...;
Christopher J. Portier christopher.portier@...;
Mark P. Mattson mark.mattson@...;
Edward J. Calabrese edwardc@...;
Thomas J. Goehl <goehl@...>;
Rebecca Renner <applepie@...>;
Linda A. Baldwin <baldwinl@...>;
M. A. Medinsky" <toxcon@...>;
D.C. Dorman <dorman@...>
*******************************************************************


Toxicological Defense Mechanisms and the Shape of Dose-Response
Relationships
Environmental Health Perspectives 106, Supplement 1, February 1998
Hormesis as a Biological Hypothesis
Edward J. Calabrese and Linda A. Baldwin
Department of Environmental Health Sciences, School of Public Health,
University of Massachusetts, Amherst, Massachusetts

Abstract
A comprehensive effort was undertaken to identify articles demonstrating
chemical hormesis.
Nearly 4000 potentially relevant articles were retrieved from preliminary
computer database searches by using various key word descriptors and
extensive cross-referencing.
A priori evaluation criteria were established including study design
features (e.g., number of doses, dose range), statistical analysis, and
reproducibility of results.
Evidence of chemical hormesis was judged to have occurred in approximately
350 of the 4000 studies evaluated.
Chemical hormesis was observed in a wide range of taxonomic groups and
involved agents representing highly diverse chemical classes, many of
potential environmental relevance.
Numerous biological end points were assessed; growth responses were the
most prevalent, followed by metabolic effects, longevity, reproductive
responses, and survival.
Hormetic responses were generally observed to be of limited magnitude.
The average low-dose maximum stimulation was approximately 50% greater
than controls.
The hormetic dose-response range was generally limited to about one order of
magnitude, with the upper end of the hormetic curve approaching the
estimated no observable effect level for the particular end point.
Based on the evaluation criteria, high to moderate evidence of hormesis was
observed in studies comprised of>6 doses; with>3 doses in the hormetic zone.
The present analysis suggests that chemical hormesis is a reproducible and
relatively common biological phenomenon.
A quantitative scheme is presented for future application to the
database. -- Environ Health Perspect 106(Suppl 1):357-362 (1998).
http://ehpnet1.niehs.nih.gov/docs/1998/Suppl-1/357-362calabrese/abstract.html
Key words: hormesis, [beta]-curve, stimulation, low dose, U-shaped

This paper is based on a presentation at The Third BELLE Conference on
Toxicological Defense Mechanisms and the Shape of Dose-Response
Relationships held 12-14 November 1996 in Research Triangle Park, NC.
Manuscript received at EHP 29 April 1997; accepted 17 July 1997.
This report was sponsored in part by an award to the University of
Massachusetts (E.J. Calabrese, Principal Investigator) by the Texas
Institute for Advancement of Chemical Technology, Inc.
Address correspondence to Dr. E.J. Calabrese, Department of Environmental
Health Sciences, School of Public Health, University of Massachusetts,
Amherst, MA 01003. Telephone: (413) 545-3164. Fax: (413) 545-4692.
E-mail: edwardc@...
Abbreviations used: LOEL, lowest observable effect level; NOEL, no
observable effect level.
[Table of Contents] [Full Article] [Citation in PubMed] [Related Articles]
Last Update: March 11, 1998

Introduction
The concept of chemical hormesis has a long history, originating over a
century ago from the research of Schulz (1), who noted that many chemicals
were able to stimulate growth and respiration of yeast at low doses but were
inhibitory at higher levels. This concept of a generalized low-dose
stimulation-high-dose inhibition was gradually supported by similar
observations with other chemicals and eventually became known as the
Arndt-Schulz law. Although Schulz (1) ushered in the so-called modern
concept of hormesis, Paracelsus (2), writing in the 16th century, likewise
noted that various toxic substances may be beneficial in small quantities.

Despite the widespread recognition of apparent hormetic effects, which
continued into the early decades of the 20th century, Stebbing (2) argues
that the Arndt-Schulz law gradually fell into disuse because it did not
provide an adequate explanatory (i.e., mechanism-based) capacity.
Nonetheless, over the years a continuing stream of observations has been
reported (2) in toxicological publications and the broader biological
literature that document low-dose stimulations.

Although there has been long-standing interest in the concept of chemical
hormesis few attempts have been made to summarize the extent of its
occurrence in biological systems and its potential to generalize with
respect to animal models, biological end points, or chemical class. Previous
limited summaries have been reported (2-6). In addition, Davis and
Svendsgaard (7) attempted to assess the statistical likelihood of low-dose
stimulation among a random sample of experimental studies published in
prominent toxicological journals. The goal of this research was to extend
the findings of these previous reports by attempting to evaluate in a
comprehensive manner those studies that are believed or alleged to display
evidence of chemical hormesis. These findings would then be employed to
assess the scientific basis of the hypothesis that hormesis is induced by
chemical agents and is a generalized biological phenomenon.

Criteria for Evaluating Hormesis
To conduct this investigation it was necessary to define chemical hormesis
and develop a priori criteria to evaluate its possible occurrence in
experimental or empirical investigations. The definition derived from
Stebbing (2) is low-dose stimulation followed by higher-dose inhibition; the
most common form of hormesis follows the widely recognized ß-curve (Figure
1). The use of the ß-curve follows principally from the widespread use of
growth as a principal end point in hormesis research. However, the term U
shaped, as emphasized by Davis and Svendsgaard (8), would most
appropriately be applied when the end point relates to a traditional
toxicologically based health end point such as cancer incidence.  The
criteria applied in the present methodology were the same for the ß-curve
and U-shaped relationships.

Figure 1. The most common dose-response curve showing hormesis--the ß-curve.

Because hormesis is a scientific hypothesis the question of whether it is
beneficial is often contextual. To eliminate subjective decisions concerning
beneficial versus harmful effects, the decision was made to evaluate model-
and end point-specific responses with respect to stimulation and inhibition.
For example, stimulation of detoxifying enzyme levels observed in the larval
form of a species would be evaluated for its hormetic potential even though
this increased metabolic activity, although beneficial in the short-term,
may have a detrimental effect on other end points. Likewise the stimulation
of microbial reproduction by antibiotics was evaluated for its hormetic
potential even though these low dose effects are harmful to the host
organism.

This assessment of chemical hormesis has been restricted to those
dose-response relationships most conforming to the ß-curve and would be
affected by the magnitude of the low-dose stimulatory response, the number
of doses establishing the reliability of the ß-curve, the presence of
statistical analysis, and the reproducibility of the findings. Within this
category only the well-known types of dose-response relationships exhibiting
ß- or U-shaped curves (represented by nutritionally essential substances,
with the exception of copper) were excluded, as this phenomenon is generally
accepted.

The capacity to evaluate high conformity to the ß-curve ideally requires the
establishment of an end point-specific lowest observable effect level (LOEL)
and no observable effect level (NOEL), with multiple doses within two orders
of magnitude immediately below the NOEL. This suggests that to be a relevant
study for the evaluation of chemical hormesis, an experiment would be
expected to have four or more doses distributed in a highly specific manner
relative to the NOEL. Therefore, highly restrictive study design
requirements must be satisfied to adequately assess chemical hormesis. Most
toxicological studies do not satisfy these design criteria and would be
classified as nonrelevant, as they are unable to demonstrate no evidence or
some evidence (i.e., equal to or greater than low evidence) of hormesis.
Similarly, data from epidemiological studies, with the exception of reports
on ethanol and cardiovascular disease, were difficult to conform to these
criteria. Within this evaluative context judgment on the evidence supporting
consistency of data from an individual experiment with the definition of
chemical hormesis was made by a weight-of-evidence procedure. It should be
noted that upward-curving ß- or U-shaped dose-response curves (e.g.,
characteristic of certain studies where low doses reduce mortality) were
included in the analysis. In addition many studies contain multiple
dose-response relationships for the same or different end points. In these
cases all end points within a study showing low-dose stimulation were
evaluated.

To facilitate an appreciation of weight-of-evidence evaluation methodology,
several graphic examples are presented that illustrate how such judgments
concerning chemical hormesis may be made (Figure 2A-E).

Figure 2. Dose-response curves illustrating various data sets evaluated for
chemical hormesis.
Figure 2A depicts a hypothetical study with a dose range of 10-fold that
displays a modest statistically insignificant increase (i.e., stimulation)
in response at the lowest dose followed by a more definitive decrease (i.e.,
inhibition). Using the criteria applied in the present methodology this
study would be judged as a) displaying an extremely limited dosage range
probably inadequate for assessment of the dynamics of the dose-response
continuum, b) inadequately describing the dose-response relationship in the
hypothetical hormetic zone, and c) having inadequate statistical power to
conclude that the stimulatory effort was treatment related. An initial
screen of such an experiment would most likely result in a designation of
not highly relevant to assess the hormesis hypothesis. However, the study
would be retained for further evaluation within a weight-of-evidence
context, based on the observation of the low-dose stimulation. At present
this experiment would be most consistent with either a low or not relevant
evidence designation of hormesis. Neither categorical placement is
convincing.

Figure 2B likewise depicts a study with a limited dose range (10-fold) with
a limited number of doses. However in contrast to Figure 2A, a more striking
stimulatory response is seen at the lowest dose, which is highly
statistically significant. However, this study is limited by having only one
dose showing a stimulatory response even though the response was impressive.
A case can be made for either a low or moderate evidence classification of
hormesis.

Figure 2C depicts a study with a markedly larger dose range (500-fold) and
number of doses (seven), with three doses in the hypothetical hormetic zone
(i.e., doses less than the NOEL). However, the magnitude of stimulation is
very limited and the observed increases are not statistically significant.
This experiment would probably be considered as no or low evidence of
hormesis. It would of course be a relevant study because of the wide dosage
range, the substantial number of doses, the inclusion of doses below the
LOEL, and the observation, although inconclusive, of stimulation at low
dose.
Figure 2D depicts a study with a very broad dose range (>1000-fold) and a
large number of doses (11), with a low-dose stimulatory response observed in
seven doses in the hypothetical hormetic zone. In addition the results
display considerable statistical power. This type of study would receive a
high evidence ranking.

Figure 2E depicts a study with a wide range of doses (>500) and a large
number of concentrations with adequate statistical power. However the data
do not show any evidence of a low-dose stimulation. This study would receive
a not relevant designation because it does not establish a NOEL nor does it
have any doses below the NOEL.

Nature and Yield of Search Strategy
Table 1 summarizes the search strategy and yield. Computerized library
searches were conducted on BIOSIS (Knight-Ridder Information, Mountain
View, CA; 1969-1996), Chemical Abstracts (Knight-Ridder Information;
1967-1996), and Medline (Knight-Ridder Information; 1966-1996) using
hormesis and the combination of U shaped plus dose response as key word
descriptors. One
hundred fifty-two publications were retrieved using hormesis as the key word
descriptor; 165 publications were retrieved using the combination of U
shaped plus dose response. Radiation hormesis was the subject of 104 of the
317 publications.

Based on information obtained from the initial searches described above,
additional search strategies were employed using the same three databases
and the following key word descriptors: low dose plus stimulation, beta
curve plus dose response, adaptation plus pollution, and homeopathy. A total
of 4058 articles was identified then reduced to 3272 following elimination
of database replication of articles. Manual review of the 3272 abstracts
revealed approximately 172 potentially relevant publications, the majority
of which were chemically oriented. Radiation studies comprised approximately
25% of the 172 articles.

A computerized library search conducted on the database Agricola
(Knight-Ridder Information; 1970-September 1995) using the key word
descriptors hormesis, U shaped plus dose response, and low dose plus
stimulation revealed very few articles not already identified in the
previous searches.

To include the most recent articles, computerized searches of the Current
Contents Life Sciences and Agricultural, Biological, and Environmental
Sciences databases (Institute for Scientific Information, Philadelphia, PA)
for the time period 15 May 1995 through 5 June 1996 were conducted using
the key word descriptors hormesis, U shaped plus dose response, low dose
plus stimulation, adaptation plus pollution, and beta curve.

Only a small number of new articles not included in the prior searches was
identified.
Potentially relevant articles not included in the computerized library
searches were obtained from extensive cross-referencing of primary sources.

Most recently additional search strategies were employed using BIOSIS,
Medline, and Chemical Abstracts and the following key word descriptors:
doses plus sublethal, doses plus subtoxic, doses plus subthreshold,
responses plus sublethal, responses plus subtoxic, and responses plus
subthreshold. A total of 5569 articles was identified then reduced to 3776
following elimination of database replication of articles. Manual review of
the 3776 abstracts revealed approximately 67 potentially relevant
publications.

A computerized library search using the same key word descriptors listed
above and the database Agricola (1970-September 1996) identified 230
articles. When reviewed approximately 25 were considered potentially
relevant. The same key word descriptors were also used in computerized
searches of the Current Contents Life Sciences and Agricultural, Biological,
and Environmental Sciences databases for the time period 16 October 1995
through 7 October 1996 to include the most recent articles. Of the 214
abstracts identified, 27 new articles were considered potentially relevant.
Finally, computer searches of Science Citations (Institute for Scientific
Infor-mation; 1990-1996) were conducted using authors' names Stebbing ARD
and Luckey TD. Approximately 400 articles were identified, of which 149 were
considered potentially relevant.

Results of Article Evaluation
Those studies placed within a high evidence category of chemical hormesis
had the greatest number of total study doses (i.e., 6.3 on average) and
doses in the so-called hormetic zone (i.e., 3.4 on average), followed by
studies demonstrating moderate evidence and more distantly by studies
demonstrating low evidence (Table 2).

The types of chemicals that induce hormetic effects represent a broad range
of chemical classes (Table 3). The most studied agents were metals, followed
by alcohols, antibiotics, auxin-related compounds, and numerous biocidal
agents. The range of hormetic responses is listed in Table 4 and indicates
that the principal end point is growth, followed by metabolic changes (e.g.,
enzyme activity), longevity, and various reproductive indices.

Characteristics of the Chemical Hormetic Zone
To assess the characteristics of the chemical hormetic dose-response zone,
experimental data were evaluated with respect to a) the dosage range of the
hormetic zone (i.e., from the estimated dosage where the response starts to
deviate from the control to the estimated dosage where the response begins
to dip below the controls); b) the maximum stimulatory response (as a
percentage greater than the control response); and c) the magnitude of
dosage difference from the maximum stimulatory response and the estimated
NOEL (Figure 3).

Figure 3. Dose-response curve depicting characteristics of the chemical
hormetic zone. ZEP, zero equivalent point.

In general the hormetic dose-response range is usually within a 10-fold
range. Stimulatory effects, however, have been reported over dosage ranges
of two or more orders of magnitude as well as over a more narrow range of
dosages depending on the agent, end point, and model assessed. The magnitude
of stimulatory responses has been observed as high as several-fold but the
majority of low-dose stimulations are 30 to 60% greater than the controls.
The distance from the maximum stimulatory response to the NOEL is difficult
to discern as it is a function of the number of doses employed, their
variability in response, and the estimated value of the NOEL. Nonetheless,
the distance between the maximum stimulatory response and the estimated
NOEL is typically observed in the 3- to 6-fold range (i.e., the NOEL is
about 3- to 6-fold greater than the maximum stimulatory response).

Hormesis as a General Biological Phenomenon
Hormetic responses are observed in numerous species from a broad range of
taxonomic groups including microbes, plants, and animals (Table 5). These
responses occur with a large number of chemicals representing a broad range
of chemical classes (Table 3). Although Stebbing (2) focused principally on
growth hormesis, the present report indicates that hormetic effects are
observed in a broad range of biological end points that involve not only
growth but survival, longevity, reproduction, and numerous metabolic and
physiological responses (e.g., metallothionein synthesis, DNA synthesis, RNA
synthesis, mitosis, oxygen consumption, altered hepatic foci, photosynthesis
rate, tissue regeneration, immune response, stress protein synthesis,
germination of seeds, etc.). Thus hormesis appears relatively common with
respect to species, chemical, and biological end point.

The ability to generalize hormetic responses also extends to the descriptive
nature of the dose-response phenomenon itself. As Stebbing (2) noted
earlier, when the data are precise and comprehensive, the points appear to
fit a ß-curve and have remarkable similarity with respect to the range and
amplitude of response. However it should be emphasized that the
developmental dynamics of the hormetic dose response over time have not been
widely or systematically studied. For example, while Stebbing (2) found that
the form of the curve varied during the course of the experiment with hydra,
Calabrese and Howe (9) observed a consistent shape of the ß-curve over 4 to
6 weeks in plant growth experiments.

Why is Hormesis Infrequently Observed?
If hormesis is believed to be relatively common, questions arise as to why
it is not reported more frequently and why the Arndt-Schulz law failed to
become established. The infrequent reports of hormesis are most likely
attributable to a combination of factors, predominantly the issue of
appropriate study design, along with the influence on safety evaluation,
which emphasizes the upper end of the dose-response continuum (i.e., where
higher concentrations establish toxic responses that can be used in chemical
evaluation and risk assessment). The present conclusions support this
assessment; a direct relationship has been shown between the strength of the
evidence supporting hormesis and the number of doses, including both overall
experimental number of doses and the number of doses in the hormetic zone.
Furthermore, because the average range of the hormetic zone is about one
order of magnitude this phenomenon is difficult to discern when wide dose
intervals (e.g., >10-fold) are used.

Predictive insight into the number of published articles potentially
displaying hormesis may be derived as follows. Assuming 500,000 toxicology
studies have been published this century (based on searches of Chemical
Abstracts, Index Medicus, and BIOSIS), it is estimated that approximately
350,000 toxicology articles have been published since 1966. Thus we assume
for the sake of argument that 500,000 toxicology papers comprise the
available pool for evaluation. If we also assume that 2% of these studies
include six or more doses (10) then 10,000 studies may contain dose ranges
adequate for hormesis evaluation. Of these 10,000 studies, based on the
characteristics defining hormetic studies, approximately 10% (i.e., 1000)
have three or more doses below the estimated NOEL. Further refinement of
this estimation can be made by assuming that 90% of these 1000 studies have
doses in the low-dose range within one to two orders of magnitude and close
to the estimated NOEL (10).

These figures suggest that mammalian toxicologists may have had only limited
direct interaction with the concept of hormesis, as only an estimated 900
potentially relevant studies exist. Therefore it is not surprising that
toxicologists may view hormesis more as a belief than a phenomenon and that
the Arndt-Schulz law (i.e., hormesis) fell into general disuse.

In addition to the low number of hormetic observations reported, Stebbing
(2) suggested that the Arndt-Schulz Law fell into disuse because it lacked
an explicit mechanism component. However, the concept of adaptation, a
potentially important explanatory component for hormesis, has evolved for
the most part independent of hormesis. Although numerous studies of
adaptation exist, only a limited number address specific mechanisms
applicable to chemically induced hormetic dose-response relationships.
Nonetheless there are studies that have sought to mechanistically explain
specific hormetic dose-response relationships.

Perhaps the most systematically assessed mechanism-based research has been
in the area of herbicide-induced stimulatory effects. Hormetic responses
have long been recognized by herbicide researchers who have conducted
studies assessing not only the molecular basis for the response but also the
effect of the plant species and age on the response.

A growing number of mammalian examples also exists where plausible
explanatory mechanisms have been put forth to account for specific hormetic
dose-response relationships (11-15).

The wide range of hormetic effects (e.g., increased growth, fecundity,
longevity, and decreased disease incidence) suggests that these changes are
fundamental and affect thousands of genes. This implies that hormetic
mechanisms are likely to be operational in a very upstream location.
Nevertheless investigators often focus on mechanisms more closely related to
biological protection. For example, substantial evidence exists in numerous
species that specific alterations in patterns of gene expression occur in
response to toxicant exposure. Such responses can be sorted into two
classes: those resulting in an enhanced metabolic capacity for
detoxification (e.g., the cytochrome P450 gene family) and those that offer
a more general protection against cellular damage caused by a wide variety
of agents (e.g., heat shock or stress proteins).

Proposed Quantitative Evaluation Scheme
A quantitative scheme has been developed to provide a more objective and
reproducible methodology for ranking studies with respect to hormetic
potential. Criteria have been established and assigned point values based
on: the number of experimental doses below the NOEL, experimental
determination or estimation of the high NOEL, the statistical significance
of the stimulatory response, the magnitude (percentage of control value) of
the stimulatory response, and the reproducibility of data by other studies
(Tables 6 and 7). Evidence of hormesis will be assessed by comparing the
summation of point values to point ranges established for six evidence
categories: high, moderate-high, moderate, low-moderate, low, and no-low
(Table 8). Results of the application of this methodology and comparison
with the current qualitative findings will be published elsewhere (16).

Summary
A goal of the present research is to create a database of studies
demonstrating objective evidence of hormesis. It is hoped that this
database, when complete, will enable the scientific community to evaluate
more rigorously and efficiently the concept of hormesis with respect to its
status as a biological hypothesis, its potential to be generalized, and its
impact on environmental and human health.

The findings to date indicate that examples of low-dose stimulation
consistent with ß-curve characteristics are copious, diverse, independently
derived, and reproducible. Yet despite the large number of such observations
no long-term systematic effort has been made to uncover explanatory
mechanisms, except in limited cases (e.g., herbicidal agents).

A more objective and reproducible evaluation methodology for ranking studies
with respect to hormetic potential is needed. The development of
quantitative criteria based on study design, response, and reproducibility
of findings is proposed and will be applied to the current database.

Furthermore, statistical simulations of dose-response relationships given
various types of variability in control groups can provide important insight
into the establishment of more quantifiable criteria in the evaluation of
possible hormetic findings. The area of hormesis and its evaluation as a
biological hypothesis has striking similarities to the evolving mathematical
area of meta-analysis in epidemiology. In fact the application of
meta-analysis techniques to the evaluation of hormetic response data is
likely to yield significant advances.

References
1. Schulz H. Ueber Hefegifte. Pfluegers Arch Gesamte Physiol Menschen Tiere
42: 517 (1888).

2. Stebbing ARD. Hormesis--the stimulation of growth by low levels of
inhibitors. Sci Total Environ 22: 213-234 (1982).

3. Townsend JF, Luckey TD. Hormoligosis in pharmacology. J Am Med Assoc
173: 44-48 (1960).

4. Luckey TD. Hormology with inorganic compounds. In: Heavy Metal Toxicity,
Safety, and Hormology, Supplement Volume 1 (Coulston F, Korte F, eds).
Stuttgart:George Thieme, 1975; 83-118.

5. Calabrese EJ, McCarthy M, Kenyon E. The occurrence of chemical
hormesis. Health Phys 57: 531-54 (1987).

6. Calabrese EJ. Primer on BELLE. In: Biological Effects of Low Level
Exposures: Dose-Response Relationships (Calabrese EJ, ed). Boca Raton,
FL:CRC/Lewis Publishers, 1994; 27-42.

7. Davis JM, Svendsgaard DJ. Nonmonotonic dose-response relationships in
toxicological studies. In: Biological Effects of Low Level Exposures:
Dose-Response Relationships (Calabrese EJ, ed). Boca Raton, FL:CRC/Lewis
Publishers, 1994; 67-86.

8. Davis JM, Svendsgaard DJ. U-shaped dose-response curves: their
occurrence and implications for risk assessment. J Toxicol Environ Health
30: 71-83 (1990).

9. Calabrese EJ, Howe KJ. Stimulation of growth of peppermint (Mentha
piperita) by phosfon, a growth retardant. Physiol Plant 37: 163-165 (1976).

10. Calabrese EJ. Unpublished data.

11. Calabrese EJ, Baldwin LA, Mehendale HM. Contemporary issues in
toxicology: G2 subpopulation in rat liver induced into mitosis by low level
exposure to carbon tetrachloride: an adaptive response. Toxicol Appl
Pharmacol 121: 1-7 (1993).

12. Calabrese EJ, Mehendale HM. A review of the role of tissue repair as an
adaptive strategy: why low doses are often non-toxic and why high doses can
be fatal. Food Chem Toxicol 34: 301-311 (1996).

13. Hart RW, Frame LT. Toxicological defense mechanisms and how they may
affect the nature of dose-response relationships. BELLE Newslett 5: 1-16
(1996).

14. Mukherjee SN, Rawal SK, Ghumare SS, Sharma RN. Hormetic
concentrations of azadirachtin and isoesterase profiles in Tribolium
castraneum (Herbst) (Coleoptera:Tenebrionidae). Experientia 49: 557-560
(1993).

15. Vichi P, Tritton TR. Stimulation of growth in human and murine cells by
adriamycin. Cancer Res 49:  2679-2682 (1989).

16. Calabrese EJ, Baldwin LA. Quantitatively-based methodology for the
evaluation of chemical hormesis. Hum Ecol Risk Assess 4: 545-554 (1997).
*******************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.aspartame
(methanol, formaldehyde) toxicity: Murray 1.24.4 rmforall

http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1056 posts in a public searchable archive  125 members

http://groups.yahoo.com/group/aspartame/messages 759 with 16,425 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L (becomes
formaldehyde in body):
EU Scientific Committee on Foods 7.12.1: Murray 1.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1037
Joe Trippi, heavy user of Diet Pepsi (aspartame toxicity), Dean's campaign
manager: Murray 11.16.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/927
Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall
********************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1054
substantial formaldehyde dose from 11% methanol of aspartame (600 mg/L  Diet
Coke): Oppermann 1973: Monte 1984: Schwarcz: Murray 1.23.4 rmforall

From: "JOE SCHWARCZ" <joe.schwarcz@...>
To: "Rich Murray" <rmforall@...>
Subject: Re: leukemia from formaldehyde in air  [from 11%  methanol in
aspartame?]: NIH NCI, Hauptmann 11.5.3: Murray 1.23.4 rmforall
Date: Friday, January 23, 2004 7:41 AM

Hi
I'm very aware of this paper because of a situation that I have
looked into myself about formaldehyde exposure in our
anatomy labs and possible risk to students.  Without a doubt
occupational exposure to inhaled formaldehyde is a real
concern.  But this has nothing to do with trace amounts of
formaldehyde derived from the diet.  Also it is interesting to
note that the study found a significantly reduced risk of non-
Hodgkin's lymphoma associated with formaldehyde exposure.
So does aspartame protect against non-Hodgkin's lymphoma?
Of course not.  That argument would be just as irresponsible
as arguing that formaledhyde from aspartame increases the
risk of leukemia based on this study.
Regards
Dr. Joe Schwarcz    Director, McGill Office for Chemistry and Society
514-398-6238  joe.schwarcz@...
*******************************************************************

From: "JOE SCHWARCZ" <joe.schwarcz@...>
To: "Rich Murray" <rmforall@...>
Subject: Re: European Union aspartame reevaluation status? Schwarcz
communications: Martini: Linsley: Murray 1.20.3 rmforall
Date: Tuesday, January 20, 2004 11:53 AM

Let me just clarify a few things.  First of all, I am not "pro-
aspartame."  I am "pro-science."  I have absolutely no reason
to support or oppose aspartame use.  I go by the published
evidence.  I do not "have a radio station in Canada": as Betty [Martini]
states but I do host an hour long science show every week.
And I did have Betty on.  Frankly, she was not very good.
Couldn't believe some of the silly things she said.  We have a
rather sophisticated audience and I had numerous e-mails after
her appearance asking me why we had such twaddle on the
air.  I think she is well-meaning and sees herself as some sort
of latter day Galileo.  She isn't.
You also say that scientists don't look at the "anti-aspartame"
literature.  Wrong.  We look at the overall picture.  Unlike
activists with preconceived ideas we do not try to fit square
pegs into round holes.  We fit the theory to the facts, not the -
other way around.
I hope your anti-aspartame campaign does not end up
increasing people's appetite for sugar.  Trading in a theoretical
risk for an established one is not a very good way to go.
Dr. Joe Schwarcz  Director, McGill Office for Chemistry and Society
514-398-6238   joe.schwarcz@...
*******************************************************************

Jan 23 2004   Hello  Joe Schwarcz,  I enjoy studying your pointed remarks.

Do you use aspartame?

The strikingly meager biochemical evidence, considering that aspartame
studies in monkeys and rats date back to the industry's Oppermann research
in 1973, justifies assuming that 30% of the 11% methanol component of
ingested aspartame remains in the body each day as formaldehye and formic
acid products in all tissues.  The problem for users is that this is by no
means "trace amounts of formaldehyde", especially since these are
cumulative, durable toxic products.  The USA EPA has set the limit for
formaldehyde in drinking water at 1 ppm, or 2 mg daily for an average use of
2 L water-- summing to
60 mg monthly.

For the common high dose of 2 L diet soda daily, as much as average daily
drinking water,  the 1120 mg aspartame immediately releases 123 mg methanol
in the GI tract, and the liver the same day converts it to formaldehyde and
formic acid.

Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.

We estimate then that the 30% retention of toxic products of formaldehyde
and formic acid in all tissues amounts to 37 mg daily,   1,200 mg monthly,
about 60 times more than the daily 0.6 mg  ( 18 mg monthly ) from 30%
retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall
*******************************************************************

I was unable with an hour search on Google to find any specific figures for
the precise amount of aspartame in Diet Coke, except for this:

This analysis by Winston Laboratories in 1997 gave the percentage of
aspartame as
0.060% in a new can, which is 600 mg per L.
I've been using a value of 555 mg/L, the average for diet sodas.

http://www.dorway.com/jcohen.html   Jennifer Cohen report in April, 1997
[extracts]
THE EFFECTS OF DIFFERENT STORAGE TEMPERATURES
ON THE TASTE AND CHEMICAL COMPOSITION OF DIET COKE
BY JENNIFER COHEN

Jennifer Cohen is an eleven-year old student in Mrs. Simmons' sixth
grade Oradell, New Jersey class.  The principal of Oradell Public School is
Scott Ryan.  He may be reached at 201 261-1181.  Jennifer conducted
an experiment proving aspartame, the artificial sweetener in diet soda,
breaks down into two deadly neurotoxins when stored at room temperature
and under refrigeration.

METHOD: I did my own experiment on aspartame.  On January 21, l997, I
bought a new case of Diet Coke from the supermarket.

Table 2                  ASPARTAME   DKP       FORMALDEHYDE
                          %           %         Parts per billion
BASELINE CAN     0.060%          *                      *

SAMPLE # 502        0.058%          0.001%          53.5
(refrigerated)

SAMPLE # 517        0.051%          0.002%         231.0  [ 0.23 mg/L]
(room temperature)

SAMPLE #540          0.026%          0.010%          76.2
(incubator)

SAMPLE # 563           *                   *                      *
(new can)

* Sample #563 (new can of Diet Coke was not tested by the lab.  It was
used for the taste test only.  The baseline can was not tested for
formaldehyde or DKP because it was assumed that FDA would ban any new
product containing poison.  The total cost of testing was $1250.  This
may not be a lot of money to a drug company but it is to me.  As it is,
I will be baby-sitting for the summer of 1997 to pay for this study. -JC)

Winston Laboratories located in Ridgefield, New Jersey,
(201-440-0022) ran the tests on the diet cokes used in this experiment.
*******************************************************************

"An average aspartame-sweetened beverage would have a conservative
aspartame content of about 555 mg/liter (48, 51)...

48.     Searle Research and Development., Aspartame for use as a
Sweetener in Carbonated Beverages. Petition submitted to the United
States Food and Drug Administration - FAP 2A3661.

51.     Staples, R.E., Teratogenicity of Formaldehyde. Formaldehyde
Toxicity. J.E. Gibson, Ed., Hemisphere Publishing Company pp 51-60
(1983)."

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall

Rereading this prescient classic review from 1984, I find its findings
are supported in much recent research, so I am again  making the full
text widely available.
[I have put my comments or corrections in square brackets, and spaced
the text to ease the reader's task]

For instance, I had forgotten this, which answers the industry PR
"science" that fruits and vegetables supply much more methanol than does
aspartame:

"Fruit and vegetables contain pectin with variable methyl ester content.
However, the human has no digestive enzymes for pectin (6, 25)
particularly the pectin esterase required for its hydrolysis to methanol
(26).

Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3).  In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6)  (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120 deg C produced
only traces of methanol (3).  Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).
Entrapment of these volatiles probably accounts for the elevation in
methanol levels of certain fruit and vegetable products during canning (31,
33).

Recent research [see links at end of post] supports his focus on the
methanol to formaldehyde toxic process:

The United States Environmental Protection Agency in their Multimedia
Environmental Goals for Environmental Assessment recommends a minimum
acute toxicity concentration of methanol in drinking water at 3.9 parts
per million, with a recommended limit of consumption below 7.8 mg/day
(8). This report clearly indicates that methanol:

"is considered a cumulative poison
due to the low rate of excretion once it is absorbed.
In the body, methanol is oxidized to formaldehyde and
formic acid; both of these metabolites are toxic." (8)....

Recently the toxic role of formaldehyde (in methanol toxicity) has been
questioned (34).  No skeptic can overlook the fact that, metabolically,
formaldehyde must be formed as an intermediate to formic acid
production (54).

Formaldehyde has a high reactivity which may be why it has
not been found in humans or other primates during methanol poisioning
(59)....

If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave.

Formaldehyde is a known
carcinogen (57) producing squamous-cell carcinomas by inhalation
exposure in experimental animals (22).  The available epidemiological
studies do not provide adequate data for assessing the carcinogenicity
of formaldehyde in man (22, 24, 57).

However, reaction of formaldehyde
with deoxyribonucleic acid (DNA) has resulted in irreversible
denaturation that could interfere with DNA replication and result in
mutation (37)...."

http://www.dorway.com/wmonte.txt

Dr. Woodrow C. Monte  Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984;  36 (1):  42-54.
(62 references)   Professsor of Food Science [retired 2002 to New Zealand]
Arizona State University,  Tempe, Arizona 85287  woodymonte@...
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% [precisely 11%] of the aspartame.
The EPA limit for water is 7.8 mg daily for methanol (wood alcohol),
a deadly cumulative poison. Many users drink 1-2 L daily.
The reported symptoms are entirely consistent with chronic methanol
toxicity.
(Fresh orange juice has 34 mg/L, but, like all juices, has 16 times more
ethanol, which strongly protects against methanol.]

ASPARTAME: METHANOL AND THE PUBLIC HEALTH
Woodrow C. Monte, Ph.D., R.D.**

ABSTRACT

Aspartame (L-asparty-L-phenylalanine methyl ester), a new sweetener
marketed under the trade name NutraSweet*,  releases into the human
bloodstream one molecule of methanol for each molecule of aspartame
consumed.

This new methanol source is being added to foods that have considerably
reduced caloric content and, thus, may be consumed in large amounts.

Generally, none of these foods could be considered dietary methanol
sources prior to addition of aspartame.
When diet sodas and soft drinks, sweetened with aspartame,
are used to replace fluid loss during exercise and physical exertion in hot
climates, the intake of methanol can
exceed 250 mg/day or 32 times the Environmental Protection Agency's
recommended limit of consumption for this cumulative toxin (8).
[ 7.8 mg daily methanol from 2 L drinking water:
8.      Cleland, J.G. and Kingsbury, G.L., Multimedia Environmental
Goals For Environmental Assessment. U.S. Environmental Protection
Agency: EPA-600/7-77-136b, E-28, November 1977. ]

There is extreme variation in the human response to acute methanol
poisoning, the lowest recorded lethal oral dose being 100 mg/kg, with
one individual surviving a dose over ninety times this level (55).

Humans, due perhaps to the loss of two enzymes during evolution, are
more sensitive to methanol than any laboratory animal; even the monkey
is not generally accepted as a suitable animal model (42).

There are no human or mammalian studies to evaluate the possible
mutagenic, teratogenic, or carcinogenic effects of chronic
administration of methyl alcohol (55).

The average intake of methanol from natural sources varies, but limited
data suggests an average intake of considerably less than 10 mg/day (8).

Alcoholics may average much more, with a potential range of between 0
and 600 mg/day, depending on the source
and in some cases the quality of their beverages (15).

Ethanol, the classic antidote for methanol toxicity,
is found in natural food sources of methanol
at concentrations 5 to 500,000 times that of the toxin (Table 1).
Ethanol inhibits metabolism of methanol and allows the body
time for clearance of the toxin through the lungs and kidneys (40, 46).

The question asked is whether uncontrolled consumption of this new
sweetener might increase the methanol intake
of certain individuals to a point beyond which
our limited knowledge of acute and chronic human
methanol toxicity can be extrapolated to predict safety.

*NutraSweet is a trademark of G.D. Searle & Co.

**Director of the Food Science and Nutrition Laboratory
Arizona State University  Tempe, Arizona 85287

[Last section of review]
METHANOL CONTENT OF ASPARTAME SWEETENED BEVERAGES

An average aspartame-sweetened beverage would have a conservative
aspartame content of about 555 mg/liter (48, 51)  and therefore, a
methanol equivalent of 56 mg/liter (56 ppm).

For example, if a 25 kg child consumed on a warm day,
after exercising, two-thirds of a two-liter bottle
of soft drink sweetened with aspartame, that child
would be consuming over 732 mg of aspartame (29 mg/kg). This alone
exceeds what the Food and Drug Administration considers the 99+
percentile daily consumption level of aspartame (48).  The child would
also absorb over 70 mg of methanol from that soft drink.  This is almost
ten times the Environmental Protection Agency's recommended daily limit
of consumption for methanol [in water].

To look at the issue from another perspective, the literature reveals
death from consumption of the equivalent of 6 gm of methanol (55, 59).
It would take 200 12 oz. cans of soda to yield the lethal equivalent of
6 gm of methanol.

According to FDA regulations, compounds added to foods that are found
to cause some adverse health effect at a particular usage level are
actually permitted in foods only at much lower levels. The FDA has
established these requirements so that an adequate margin of safety
exists to protect particularly sensitive people and heavy consumers of
the chemical.
Section 170.22 of Title 21 of the Code of Federal Regulations
mandates that this margin of safety by 100-fold below the
"highest no-effect" level.

If death has been caused by the methanol equivalent of 200 12 oz. cans
of aspartame sweetened soda, one hundredth of that level
would be two cans of soda.

The relationship of the lethal dose to the "highest no effect" level
has tragically not been determined for methanol (9, 11) but assuming very
conservatively that the level is one tenth of the lethal dose, the FDA
regulations should have limited consumption to approximately 2.4 ounces
of aspartame sweetened soft drink per day. [Published case reports show
severe reactions to tiny doses of aspartame in some reactors: 1.5, 4, or
6-8 mg aspartame, while a 12 oz can of diet soda provides about 200 mg
aspartame.]

The FDA allows a lower safety margin only when "evidence is submitted
which justifies use of a different safety factor." (21.C.F.R.170.22)
No such evidence has been submitted to the FDA for methanol.

Thus, not only have the FDA's requirements for acute toxicity not been
met, but also, no demonstration of chronic safety has been made. The
fact that methyl alcohol appears in other natural food products
increases greatly the danger of chronic toxicity developing by adding
another unnatural source of this dangerous cumulative toxin to the food
system.

NATURAL SOURCES OF METHANOL

Methanol does appear in nature.

To determine what impact the addition of a toxin will have on an
environment it is very helpful to accurately determine the background
levels of consumption.

Fruit and vegetables contain pectin with variable methyl ester content.
However, the human has no digestive enzymes for pectin (6, 25)
particularly the pectin esterase required for its hydrolysis to methanol
(26).

Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3).  In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6) (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120? C produced
only traces of methanol (3). Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).  Entrapment of
these volatiles probably accounts for the elevation in methanol levels of
certain fruit and vegetable products during canning (31, 33).

In the recent denial by the Food and Drug Administration of my request
for a public hearing on this issue (13), the claim is made by them that
methanol occurs in fruit juices at an average of 140 parts per million
(a range of between 15-640 parts per million). This often used average
originates from an informative table in a conference paper presented by
Francot and Geoffroy (15). The authors explain that the data presented
in the table "may not" represent their work but "other authors" (15).

There is no methodology given nor is the original source cited and only
the identity of the lowest methanol source, grape juice (12 ppm), and
the highest, black currant (680 ppm), are revealed. The other 22 samples
used to generate this disarmingly high average are left completely to
the imagination.

The authors conclude their paper by insisting that "the
content of methanol in fermented or non-fermented beverages should not
be of concern to the fields of human physiology and public health."
They imply that wines "do not present any toxicity" due to the presence
of certain natural protective substances (15).

When they present their original data
relating to the methanol content of French wines (range 14-265 ppm)
or when the methanol content of any alcoholic beverage is given,
the ration of methanol to ethanol is also presented. Of the wines
they tested, the ratio associated with the highest methanol content
(265 ppm) indicates over 262 times as much ethanol present as methanol.

The scientific literature indicates that a fair estimate of methanol
content of commonly consumed fruit juices is on the order of 40 parts
per million (Table 1).  Stegink, et al. Points out that some neutral spirits
contain as much as 1.5 grams/liter of methanol (51); what is not
mentioned is the fact that if these spirits are at least 60 proof
(30% ethanol) this still represents the presence of over 200 molecules
of ethanol for every molecule of methanol that is digested.

An exhaustive search of the present literature indicates that no testing
of natural substances has ever shown methanol appearing alone; in
every case ethanol is also present, usually, in much higher
concentrations (15, 27, 28, 30, 31, 35, 44, 45).

Fresh orange juices can have very little methanol (0.8 mg/liter), and
have a concomitant ethyl alcohol content of 380 mg/liter (28).

Long term storage in cans has a tendency to cause an increase in these
levels, but even after three years of storage, testing has revealed only
62 mg/liter of methanol, with an ethanol content of 484 mg/liter. This
is a ratio of almost eight times ethanol/methanol (28).

Testing done recently in Spain showed orange juice with
33 mg/liter methanol and 651 mg/liter ethanol (20/1 ratio) (45).

The range for grapefruit juices are similar, ranging
from 0.2 mg methanol/liter (27) to 43 mg methanol/liter (27).

The lowest ratio of any food item was found in canned grapefruit
sections with 50-70 mg/liter methanol and 200-400 mg/liter ethanol (27),
thus averaging six molecules ethanol for every molecule of methanol.

This high ethanol to methanol ratio, even at these low ethanol
concentrations, may have some protective effect. As stated previously,
ethanol slows the rate of methanol's conversion to formaldehyde and
formate allowing the body time to excrete methanol in the breath and
urine. Inhibition is seen in vitro even when the concentration of ethyl
alcohol was only 1/16th that of methanol (62). The inhibitory effect is
a linear function of the log of the ethyl alcohol concentration, with a
72% inhibition rate at only a 0.01 molar concentration of ethanol (2).

Therefore if a liter of a high methanol content orange juice is
consumed, with 33 mg/liter of methanol and a 20/1 ration of
ethanol/methanol, only one molecule of methanol in 180 will be
metabolized into dangerous metabolites until the majority of the ethanol
has been cleared from the bloodstream.

If a similar amount of methanol equivalent from aspartame were consumed,
there would be no competition (46).

Another factor reducing the potential danger associated with methanol
from natural juices is that they have an average caloric density of 500
Kcal/liter and high osmolarity which places very definite limits to
their consumption level and rate.

Data obtained in a Department of Agriculture survey of the food intake
of a statistically sampled group of over 17,000 consumers nationwide
(1), indicate that the 17.6% of the population that consume orange juice
daily take in an average of 185.5 gm of that juice. These statistics
indicate that 1.1% of the population consume an average of 173.9 gm of
grapefruit juice while only 1.8% drink approximately 201 gm of tomato
juice daily. Table 1 shows that under normal conditions these
individuals would only be expected to consume between 1 and 7 mg of
methanol a day from these sources. Even if an individual consumed two
juices in the same day or a more exotic juice such as black currant,
there would still be some protection afforded by the ethanol present in
these natural juices.

Consumption of aspartame sweetened drinks at
levels commonly used to replace lost fluid during exercise yields
methanol intake between 15 and 100 times these normal intakes (Table 1).

This is comparable to that of "winos" but without the metabolic reprieve
afforded by ethanol. An alcoholic consuming 1500 calories a day from
alcoholic sources alone may consume between 0 and 600 mg of methanol
each day depending on his choice of beverages (Table 1).

The consumption of aspartame sweetened soft drinks or other beverages is
not limited by either calories or osmolarity, and can equal the daily
water loss of an individual (which for active people in a state like
Arizona can exceed 5 liters). The resultant daily methanol intake might
then rise to unprecedented levels.

Methanol is a cumulative toxin (8)
and for some clinical manifestations it may be a human-specific toxin.

CONCLUSION

Simply because methanol is found "naturally" in foods, we can not
dismiss the need for carefully documented safety testing in appropriate
animal models before allowing a dramatic increase in its consumption.

We know nothing of the mutagenic, teratogenic or carcinogenic effect of
methyl alcohol on man or mammal (55, 59).  Yet, if predictions are
correct (5), it won't be long before an additional 2,000,000 pounds of
it will be added to the food supply yearly (53).

Must this, then, constitute our test of its safety?
********************************************************************

The only research that I've heard about that could have studied the actual
biochemical residuals of aspartame in humans only used three humans and did
not attempt using C-14 labelled methanol, although they did test both C-14
labelled phenylalanine and aspartic acid separately in their aspartame.

Their report in 1976 included only three human subjects, who were tested
with aspartame made with C-14 phenylalanine and then C-14 aspartate--
but never the methanol component!   Instead of mentioning the dreaded word
"formaldehyde" anywhere in the text and citations, they only showed, on
Figure 1,  Metabolic pathways followed by aspartame,  using arrows to show
reaction paths,

Asp-Phe-Me -->  intestinal esterases ---> Asp-Phe  +  MeOH  -->
one-carbon metabolic pool  -->  CO2 +  formyl metabolites

J Toxicol Environ Health. 1976 Nov; 2(2): 441-51.
Comparative metabolism of aspartame in experimental animals and humans.
Ranney RE, Oppermann JA, Muldoon E, McMahon FG.

Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid,
methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening
agent that organoleptically has about 180 times the sweetness of sugar.
The metabolism of aspartame has been studied in mice, rats, rabbits, dogs,
monkeys, and humans.
The compound was digested in all species in the same way as are natural
constituents of the diet.
Hydrolysis of the methyl group by intestinal esterases yielded methanol,
which was oxidized in the one-carbon metabolic pool to CO2.
The resultant dipeptide was split at the mucosal surface by dipeptidases and
the free amino acids were absorbed.
The aspartic acid moiety was transformed in large part to CO2 through its
entry into the tricarboxylic acid cycle.
Phenylalanine was primarily incorporated into body protein either unchanged
or as its major metabolite, tyrosine.   PMID: 827618

Their 1973 report clearly showed that 30% of C-14 labelled methanol in oral
aspartame was no longer being excreted from small monkeys after 8 hours.
What could this possibly be except toxic residuals in all body tissues of
the only possible biochemical products, formaldehyde and formic acid, both
cumulative?

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.

By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

These dire possibilities were confirmed in rats by the Trocho study in 1998.

The hundreds of case reports by aspartame reactors are entirely consistent
with chronic long-term, low-level toxicity from methanol or formaldehyde.

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall
[selection]
"These are indeed extremely high levels for adducts of formaldehyde, a
substance responsible of chronic deleterious effects (33), that has also
been considered carcinogenic (34,47). The repeated occurrence of claims
that aspartame produces headache and other neurological and
psychological secondary effects-- more often than not challenged by
careful analysis-- (5,9,10,15,48) may eventually find at least a partial
explanation in the permanence of the formaldehyde label, since
formaldehyde intoxication can induce similar effects (49).

The cumulative effects derived from the incorporation of label in the
chronic administration model suggests that regular intake of aspartame
may result in the progressive accumulation of formaldehyde adducts.

It may be further speculated that the formation of adducts can help to
explain the chronic effects aspartame consumption may induce on
sensitive tissues such as brain (6,9,19,50). In any case, the possible
negative effects that the accumulation of formaldehyde adducts can
induce is, obviously, long-term. The alteration of protein integrity
and function may needs some time to induce substantial effects.

The damage to nucleic acids, mainly to DNA, may eventually induce cell
death and/or mutations.

The results presented suggest that the conversion of aspartame methanol
into formaldehyde adducts in significant amounts in vivo should be
taken into account because of the widespread utilization of this
sweetener. Further epidemiological and long-term studies are needed to
determine the extent of the hazard that aspartame consumption poses for
humans."

http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M  ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo.  Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male)  alemany@...

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ].  Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@...    919-684-3303, 660-5657
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall ]

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall
******************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1044
aspartame and formaldehyde toxicity discussion:
Schwarcz: Murray 12.13.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1049
let us examine an aspartame reactor: Schwarcz: Murray 1.18.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1053
leukemia from formaldehyde in air  [from 11% methanol in aspartame?]: NIH
NCI, Hauptmann 11.5.3: Murray 1.23.4 rmforall
http://www.ajc.com/health/content/shared-auto/healthnews/occu/515908.html
*******************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1054 posts in a public searchable archive  125 members

http://groups.yahoo.com/group/aspartame/messages 759 with 16,425 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L (becomes
formaldehyde in body):
EU Scientific Committee on Foods 7.12.1: Murray 1.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall
*******************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1053
leukemia from formaldehyde in air  [from 11% methanol in aspartame?]: NIH
NCI, Hauptmann 11.5.3: Murray 1.23.4 rmforall
http://www.ajc.com/health/content/shared-auto/healthnews/occu/515908.html

Health News Archives

Formaldehyde Linked to Leukemia, Lung Cancer

THURSDAY, Nov. 6 (HealthDayNews) -- Formaldehyde, the pungent chemical used
in everything from insect preservation to film manufacturing, may boost
rates of leukemia in exposed workers, a major federal analysis finds.

And a new study from the United Kingdom suggests such workers also face a
greater lung cancer risk from formaldehyde exposure, although they only face
a tiny risk of some rarer cancers.

While the U.S. researchers acknowledge other studies haven't been as
definitive about the potential risk, the new reports are certain to fuel the
debate over the use of the chemical in American factories. Federal
regulations have limited exposure to formaldehyde since the 1980s.

However, some experts continue to call for less research and more
restrictions.
"We need more science like we need a hole in the head," says Dr. Samuel S.
Epstein, professor emeritus of environmental and occupational medicine at
the University of Illinois School of Public Health.

For the U.S. study, Michael Hauptmann, a biostatistics researcher at the
National Cancer Institute, and his colleagues launched the largest-ever
analysis of formaldehyde exposure. They examined the medical records of
25,619 workers who began working with formaldehyde before 1966 at 10
industrial plants. Researchers followed the workers through 1994.

Those exposed to high levels of formaldehyde were up to 3.5 times more
likely to develop leukemia than those at the lowest levels. In total, 69 of
the those workers died of leukemia.

While the number of deaths is small, the link between formaldehyde and
leukemia is important, Hauptmann says.

"The study definitely suggests that exposure should be kept to a minimum in
the workplace and the environment," he adds.

The number of American workers exposed to formaldehyde on the job appears to
be unknown, but federal officials estimated the number at 1.5 million from
1981-1983.
Most of the workers are exposed to formaldehyde during various types of
manufacturing, including the production of particle board, plywood, plastic
and photographic film, Hauptmann says.

Scientists and pathologists also work with formaldehyde, which acts as a
preservative and gives laboratories their distinct smell. Other uses include
the manufacture of permanent press clothing, embalming fluid and cosmetics.

"It usually comes in a liquid form from which solutions are prepared,"
Hauptmann says. "Then there is formaldehyde gas released that you can
inhale."

His findings appear in the Nov. 5 issue of the Journal of the National
Cancer Institute.
In the other study, which appears in the same issue, researchers in the
United Kingdom examined the medical histories of 14,014 British men who were
exposed to formaldehyde after 1937. The study had been completed in the late
1990s, but the researchers extended it to 2000.

Research in animals has suggested that formaldehyde could contribute to two
rare types of nasal cancer, but the number of deaths from them -- three --
were actually lower than those that would have otherwise been expected.
However, the workers were up to 1.6 times more likely to die of lung cancer.

It's not clear how formaldehyde may lead to leukemia and lung cancer. One
possibility is that the chemical launches itself into the body on tiny
particles in the air and then works itself free to create damage, Hauptman
says.

Epstein says both findings are "more than enough to warrant the toughest
regulatory proposals."

To learn more about the use of formaldehyde in industry, visit the
Occupational Safety & Health Administration or try the New York Committee
for Occupational Safety & Health.
© 2004 The Atlanta Journal-Constitution
*******************************************************************

http://dceg2.cancer.gov/pdfs/hauptmann9516152003.pdf

J Natl Cancer Inst. 2003 Nov 5; 95(21): 1615-23.
Mortality from lymphohematopoietic malignancies among workers in
formaldehyde industries.
Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A.   hauptmann@...
lubinj@...  ps85a@...  hayesr@...
aaron.blair@...
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services,
Bethesda, MD 20892.

BACKGROUND: Many U.S. factory workers are exposed to formaldehyde.
Although increased risks for leukemia have been found in medical workers and
other professionals exposed to formaldehyde, studies in industrial workers,
who are thought to have higher exposures, have shown inconsistent
associations.
We extended follow-up of a cohort of industrial workers to evaluate the
association between formaldehyde exposure and lymphohematopoietic cancers.
METHODS: The cohort consisted of 25 619 workers (865 708 person-years)
employed before January 1, 1966, at one of 10 U.S. industrial plants and
followed through December 31, 1994.
We analyzed formaldehyde exposure (peak exposure, average exposure
intensity, cumulative exposure, and duration of exposure) and mortality from
lymphohematopoietic malignancies using standardized mortality ratios and
relative risks and 95% confidence intervals (CIs) based on Poisson
regression.
Statistical tests were two-sided.
RESULTS: Among the cohort, there were 178 deaths from lymphohematopoietic
malignancies. Relative risks for leukemia (69 deaths), particularly for
myeloid leukemia (30 deaths), increased with formaldehyde exposure.
Compared with workers exposed to low peak levels of formaldehyde (0.1-1.9
ppm), relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25)
and 3.46 (95% CI = 1.27 to 9.43) for workers exposed to peak levels of
2.0-3.9 ppm and > or = 4.0 ppm, respectively (P(trend) =.009).
Compared with workers exposed to low levels of average exposure intensity of
formaldehyde (0.1-0.4 ppm), workers exposed to 0.5-0.9 ppm and > or = 1.0
ppm average intensity had relative risks of 1.15 (95% CI = 0.41 to 3.23) and
2.49 (95% CI = 1.03 to 6.03), respectively (P(trend) =.088).
The relative risk for leukemia was not associated with cumulative exposure
but was weakly associated with duration of exposure.
Relative risks for Hodgkin's disease also increased with formaldehyde
exposure. CONCLUSIONS: Exposure to formaldehyde may cause leukemia,
particularly myeloid leukemia, in humans.
However, results from other investigations are mixed, suggesting caution in
drawing definitive conclusions.  PMID: 14600094
*******************************************************************

http://dceg2.cancer.gov/pdfs/hauptmann9516152003.pdf

J Natl Cancer Inst 2003; 95: 1615-23.
Mortality From Lymphohematopoietic Malignancies
Among Workers in Formaldehyde Industries
Michael Hauptmann, Jay H. Lubin, Patricia A. Stewart, Richard B. Hayes,
Aaron Blair
Affiliation of authors: Division of Cancer Epidemiology and Genetics,
National
Cancer Institute, National Institutes of Health, Department of Health and
Human Services, Bethesda, MD.
Correspondence to: Michael Hauptmann, PhD, Division of Cancer Epidemiology
and Genetics, National Cancer Institute, 6120 Executive Blvd., Bethesda,
MD 20892 (e-mail: hauptmann@...).
See "Notes" following "References."
DOI: 10.1093/jnci/djg083
Journal of the National Cancer Institute, Vol. 95, No. 21, © Oxford
University
Press 2003, all rights reserved.
Journal of the National Cancer Institute, Vol. 95, No. 21, November 5, 2003

Approximately 12 million tons of formaldehyde, a flammable
and colorless gas, were produced worldwide in 1992
(1). Formaldehyde is used in the production of resins, molding
compounds, photographic film, decorative laminates, and
plywood, and as a bactericide and a tissue preservative. The
U.S. National Institute of Occupational Safety and Health
estimated that, in 1981-1983, approximately 1.5 million workers
in the United States were exposed to formaldehyde (2). Occupational
exposures occur mainly to formaldehyde gas. However,
formaldehyde-containing particulates can occur as products (i.e.,
paraform) or can be formed when formaldehyde gas adheres to
page 1615

carrier agents such as wood dust. Dermal exposure is possible
from formalin solutions or liquid resins (3).

Formaldehyde at a concentration of approximately 0.5-1 ppm
causes acute health effects, including irritation of the eye and upper
airway mucosa (3). Rats and mice that were exposed by inhalation
to formaldehyde gas at concentrations of greater than 5 ppm for 2
or more years developed squamous cell carcinomas of the nasal
cavity (4,5). However, formaldehyde can have effects away from
the site of exposure. Human leukocytes exposed to formaldehyde
developed DNA-protein cross-links in vitro and in vivo, which may
result in a loss of genetic material (6).

The International Agency for Research on Cancer found
sufficient evidence to declare that formaldehyde is carcinogenic
in animals but only limited evidence for carcinogenicity in
humans (3). However, formaldehyde exposure has been associated
with cancer of the nasal sinuses and nasopharynx in some
studies of industrial workers (3). Although some studies have
reported an increased risk of leukemia (range of standardized
mortality ratios [SMRs] 
 1.1-3.0) among medical workers and
other professionals exposed to formaldehyde, the results of
studies among industrial workers are mixed (3). We previously
assessed mortality among the largest cohort of industrial workers
exposed to formaldehyde (7). Here, we extended follow-up
of the cohort by 15 years, and assessed the relationship between
formaldehyde exposure and lymphohematopoietic malignancies.

SUBJECTS AND METHODS
Cohort Design and Follow-up
Details of the study design have been described previously
(7,8). In brief, the cohort consisted of 25,619 workers first
employed at one of 10 industrial plants before January 1, 1966
(878 workers of unknown sex or race/ethnicity and 64 workers
who started work after January 1, 1966, were excluded). In the
original follow-up (7), information for each worker regarding
birth date, race/ethnicity, sex, and each job held at a participating
plant was obtained from company records. Subjects were followed
from the year of initial cohort identification (1934-1958,
depending on the plant) or first employment at a plant, whichever
was later, through January 1, 1980. Data from the Social
Security Administration, Health Care Finance Administration,
Veterans Administration, credit bureaus, motor vehicle departments,
and telephone directories were used to determine vital
status. Death certificates were obtained for 4,349 individuals
through 1980 to determine the underlying cause of death. For the
866 subjects (3.4%) lost to follow-up, follow-up ended at the last
date known alive.

In this study, we extended the mortality follow-up through
December 31, 1994. All subjects alive on January 1, 1980, were
linked to the National Death Index Plus (http://www.cdc.gov/nchs/
r&d/ndi/ndi.htm). For deceased individuals, information was collected
from death certificates to establish the underlying cause of
death. A total of 4,137 new deaths were identified. The total number
of deaths for the cohort was therefore 8,486. The remaining subjects
were assumed to be alive on December 31, 1994.

During this study, we did not contact study participants. Therefore,
the institutional review board of the National Institutes of
Health (Bethesda, MD) determined that the study was exempt from
review. Approval was obtained from state institutional review
boards, where necessary, to obtain death certificates.

Exposure Assessment
The 10 industrial plants included in this study produced formaldehyde
(three plants), formaldehyde resins (six plants), molding
compounds (six plants), molded plastic products (two plants), photographic
film (two plants), and plywood (one plant). Exposure to
formaldehyde was estimated from work histories collected through
1980 on the basis of job titles, tasks, visits to the plants by study
industrial hygienists, discussions with workers and plant managers,
and monitoring data. Peak exposures were defined as short-term
exposures (generally 15 minutes) that exceeded the 8-hour, timeweighted
average formaldehyde exposure intensity. Peak exposures
in the workplace occurred from routine (i.e., hourly, daily, or
weekly) or nonroutine high-exposure tasks or from working in
areas where nonroutine unusual upsets or events, such as spills,
occur. No measurements of peak exposure were available in this
study. Peak exposures were therefore estimated by an industrial
hygienist from knowledge of the job tasks and a comparison with
the 8-hour time-weighted average. The presence of particulates (i.e.,
solid formaldehyde such as paraform or trioxane), a formaldehydecontaining
resin or molding compound particulate, or a particulate
onto which formaldehyde gas could be adsorbed, was assessed. The
routine use of respirators was determined. We identified exposures
to 11 other widely used chemicals in the plants (i.e., antioxidants,
asbestos, carbon black, dyes and pigments, hexamethylenetetramine,
melamine, phenol, plasticizers, urea, wood dust, and benzene).
We also identified workers employed as chemists or laboratory
technicians. A comprehensive description of the exposure
assessment is given elsewhere (7,9,10). No information on formaldehyde
exposure after 1980 was available.

Statistical Analysis
Subjects contributed person-years from the time of entry into the
cohort (1934-1966) through time of death or December 31, 1994,
whichever was earlier. For each job, the following was available:
8-hour time-weighted average formaldehyde exposure intensity (in
ppm), peak formaldehyde exposure category (unexposed, 0.1-1.9
ppm, 2.0-3.9 ppm, 
4 ppm), frequency of peak exposure (none,
hourly, daily, weekly, monthly), presence of particulates (yes/no),
routine respirator use (yes/no), exposure to each of 11 other substances
(yes/no), and working as a chemist or laboratory technician
(yes/no). On the basis of this information, the following exposure
variables were calculated as time-dependent variables: cumulative
formaldehyde exposure (in ppm-years), average formaldehyde exposure
intensity (in ppm), and highest peak formaldehyde exposure
category. In addition, we calculated duration of formaldehyde exposure
(in years) because this measure is widely used in occupational
epidemiologic studies. However, the validity of exposure
duration requires the assumption that the exposure rate for all jobs
and over time be constant, which was not true in this, and most
similar, situations. We also calculated exposure to formaldehydecontaining
particulates (ever/never), duration of exposure to each of
11 other substances (in years), and duration of working as a chemist
or laboratory technician (in years). Cut points for formaldehyde
exposure categories were approximately the 60th and 80th percentiles
of the distribution of the respective exposure measure in
exposed subjects who died from cancer. These cut points ensured
that there were sufficient numbers of case subjects in the exposed
categories.

SMRs were calculated using sex-, race-/ethnicity-, age-, and
calendar year-specific U.S. mortality rates. For internal analy-
page 1616

ses, relative risks and 95% confidence intervals (CIs) were
estimated using log-linear Poisson regression models (11) stratified
by calendar year (1930-1934, 1935-1939, . . . , 1990-
1994), age (0-14, 15-19, . . . , 75-79, 80), sex, and race/ethnicity
(black/white) and adjusted for pay category (annual salary/
hourly wage/unknown). The low-exposure categories (i.e., 0.1-
1.9 ppm for peak exposure, 0.1-0.4 ppm for average exposure
intensity, 0.1-1.4 ppm-years for cumulative exposure, and 0.1-
4.9 years for duration of exposure) were used as the reference
categories to minimize the impact of any unmeasured confounding
variables because unexposed workers may have differed
from exposed workers with respect to socioeconomic characteristics.
However, workers in the low-exposure categories were
exposed to very low levels of formaldehyde and are thus an
appropriate referent group. Potential confounding was evaluated
for exposure to 11 other substances (listed above) and for
working as a chemist or laboratory technician. Tests of trend for
categorical variables were based on the likelihood ratio for the
slope of the corresponding continuous variable, with the exception
of peak exposure, for which categorical ranks were used.
Heterogeneity among risk estimates was assessed by likelihood
ratio tests. Tests were two-sided at a 5% significance level.
EPICURE software (12) was used for the analysis.

All exposures were calculated using a 2-year lag interval to
account for latency, i.e., for the fact that formaldehyde exposures
received within 2 years before death are unlikely to be
associated with the cause of death. We evaluated various lag
intervals from 2 to 20 years and did not find substantial differences
in goodness of model fit from the 2-year lag interval (data
not shown).

Relative risk estimates were not adjusted for plant because
plant is highly correlated with exposure. However, we repeated
the analyses, selectively omitting one plant at a time, and found
relative risk estimates to be similar to those from the analysis
that included all plants (data not shown).

RESULTS
Demographic Description of the Cohort
The cohort included 25,619 subjects, 75% of whom entered
the cohort before 1960, and 865 708 person-years. The duration
of follow-up ranged from a few days to 58 years, with a median
duration of 35 years. Median ages at entry and end of follow-up
were 26 and 64 years, respectively. The majority of the cohort
were white men (81%) (Table 1). Less than 20% of the cohort
consisted of white women (12%), black men (7%), or black
women (1%) (Table 1).

Exposure to Formaldehyde
The median time-weighted average formaldehyde exposure
intensity for workers in jobs exposed to formaldehyde was 0.5
ppm (range 
 0.0-4.3 ppm), and 17% of all jobs and 3201
individuals had no exposure to formaldehyde. Of all jobs, 2.6%
had average exposure intensities of 2 ppm or higher, and 14.3%
had peak exposures of 4 ppm or higher. These exposures were
generally similar to or slightly higher than those in other studies
examining occupational exposures to formaldehyde (13). The
median duration in jobs with exposure to formaldehyde was 2
years (range 
 1 day to 46 years). Cumulative exposure to
formaldehyde ranged from zero to 107 ppm-years. Approximately
0.5% (n 
 133) of the individuals in the cohort ever
routinely used a respirator and, of these, only 24 individuals
used one routinely for 5 or more years.

Formaldehyde Exposure and Mortality
Among the 2,099 cancer deaths in the cohort, there were 178
deaths from lymphohematopoietic malignancies: 17 among un--
exposed workers, and 161 among exposed workers (Table 2).
Compared with mortality among the U.S. population, mortality
from all causes, all cancers, and all lymphohematopoietic malignancies
was statistically significantly lower among workers,
regardless of exposure status. For unexposed workers, the SMRs
for mortality from all causes, all cancers, and all lymphohematopoietic
malignancies were 0.77 (95% CI 
 0.72 to 0.83), 0.65
(95% CI 
 0.56 to 0.75), and 0.62 (95% CI 
 0.39 to 1.00),
respectively. For exposed workers, the SMRs for mortality from
all causes, all cancers, and all lymphohematopoietic malignancies
were 0.95 (95% CI 
 0.93 to 0.97), 0.90 (95% CI 
 0.86
to 0.94), and 0.80 (95% CI 
 0.69 to 0.94), respectively. In
exposed workers, there were statistically significantly fewer
deaths than expected from non-Hodgkin's lymphoma (SMR

 0.61, 95% CI 
 0.46 to 0.83), whereas there were more
deaths than expected from Hodgkin's disease (SMR 
 1.26,
95% CI 
 0.81 to 1.95), although the increase was not
statistically significant. Among unexposed workers, there
were statistically significantly fewer deaths than expected
from leukemia (SMR 
 0.38, 95% CI 
 0.14 to 1.00) and
more deaths than expected from multiple myeloma (SMR 

1.23, 95% CI 
 0.51 to 2.95), although the increase was not
statistically significant.

The relative risks for leukemia (69 deaths) increased by peak
and average level of exposure to formaldehyde, particularly for
myeloid leukemia (30 deaths). Compared with workers exposed
page 1617

Table 1. Demographic characteristics of the cohort


Demographic
characteristic No. of subjects (%) Person-years (%)
Ethnicity and sex
Men
White 20 658 (81) 702 371 (81)
Black 1835 (7) 56 467 (7)
Women
White 3100 (12) 106 065 (12)
Black 26 (1) 805 (1)
Year of entry into cohort
Before 1945 3105 (12) 118 398 (14)
1946-1955 11 200 (44) 399 384 (46)
1956-1965 11 314 (44) 347 927 (40)
Age at entry, y
30 16 877 (66) 601 727 (70)
31-40 5122 (20) 170 793 (20)
41-50 2593 (10) 72 557 (8)
51-60 838 (3) 18 055 (2)

61 189 (1) 2577 (1)
Duration of follow-up, y
30 8273 (32) 172 723 (20)
31-35 5092 (20) 169 630 (20)
36-40 5109 (20) 195 628 (23)

41 7145 (28) 327 727 (38)
Vital status
Alive 16,267 (64) 633 576 (73)
Deceased 8,486 (33) 228 050 (26)
Unknown 866 (3) 4,081 (1)
Total 25,619 (100) 865 708 (100)

Percentages may not add up to 100 due to rounding.
page 1617

to low levels of formaldehyde (0.1-1.9 ppm peak exposure or
0.1-0.4 ppm average exposure intensity), relative risks for myeloid
leukemia were 2.43 (95% CI 
 0.81 to 7.25) and 3.46
(95% CI 
 1.27 to 9.43) for workers exposed to formaldehyde
at 2.0-3.9 ppm and 
4.0 ppm peak exposure, respectively
(Ptrend 
 .009), and 1.15 (95% CI 
 0.41 to 3.23) and 2.49 (95%
CI 
 1.03 to 6.03) for workers exposed to formaldehyde at
0.5-0.9 ppm and 
1.0 ppm average exposure intensity, respectively
(Ptrend 
 .088) (Tables 3 and 4). When we excluded peak
exposures in jobs of short duration (1 year) or peaks that
occurred less often than daily, relative risks for all leukemia
associated with peak exposure were not substantially changed.
The association of duration of exposure with leukemia was
weak, and there was no association of cumulative exposure with
leukemia (Tables 5 and 6).

Increased relative risks for all leukemia by peak and average
intensity of formaldehyde exposure were similar within categories
of age, pay, exposure to formaldehyde-containing particulates,
and employment as a chemist or laboratory technician
(data not shown).

Table 3. Relative risks for mortality from lymphohematopoietic malignancies
by peak exposure to formaldehyde

Cause of death (ICD?)
Relative risk (95% confidence interval)?
Ptrend§ Ptrend

No. of deaths
Peak exposure, ppm¶
0 0.1-1.9 2.0-3.9 
4.0
Lymphohematopoietic malignancies (200-209) 1.08 (0.60 to 1.94) 1.00
(Referent) 1.71 (1.14 to 2.58) 1.87 (1.27 to 2.75) .002 .002
17 48 49 64
Non-Hodgkin's lymphoma (200, 202) 1.12 (0.38 to 3.31) 1.00 (Referent) 1.39
(0.67 to 2.91) 1.23 (0.59 to 2.55) .604 .536
5 15 14 15
Hodgkin's disease (201) 0.51 (0.06 to 4.52) 1.00 (Referent) 3.45 (0.98 to
12.16) 3.35 (0.97 to 11.59) .014 .042
1 5 7 8
Multiple myeloma (203) 2.10 (0.66 to 6.75) 1.00 (Referent) 1.48 (0.56 to
3.92) 1.67 (0.68 to 4.12) .669 .355
5 9 8 11
Leukemia (204-207) 0.78 (0.25 to 2.43) 1.00 (Referent) 2.04 (1.04 to 4.01)
2.46 (1.31 to 4.62) .001 .004
4 16 20 29
Lymphatic leukemia (204) 0.00 (0.00 to 2.24) 1.00 (Referent) 1.51 (0.48 to
4.74) 1.39 (0.46 to 4.17) .279 .559
0 6 6 7
Myeloid leukemia (205) 0.67 (0.12 to 3.61) 1.00 (Referent) 2.43 (0.81 to
7.25) 3.46 (1.27 to 9.43) .003 .009
2 6 8 14
Other/unspecified leukemia (207) 1.92 (0.33 to 11.33) 1.00 (Referent) 2.33
(0.63 to 8.66) 2.47 (0.69 to 8.87) .277 .154
2 4 6 7
No. of person-years 135 396 335 923 194 468 199 921

Analyses were not feasible for polycythemia vera (ICD 208, one death) and
myelofibrosis (ICD 209, five deaths) due to small numbers. No association
with
formaldehyde exposure was observed for other diseases of blood cells in the
bone marrow, including seven deaths from anemia of which four were aplastic,
one
was hypochromic with iron loading, one was specified as other, and one was
unspecified, and three deaths from agranulocytosis.
?Codes of the International Classification of Diseases (ICD), 8th revision.
?Relative risks were derived from Poisson regression stratified for calendar
year, age (both in 5-year intervals), sex, and race/ethnicity (black/white),
and adjusted
for pay category (salary/wage). Cut points for formaldehyde exposure
categories were approximately the 60th and 80th percentiles of the
distribution of the respective
exposure measure in exposed subjects who died from cancer. These cut points
ensured that there were sufficient numbers of cases in the exposed
categories.
§Two-sided likelihood ratio test (1 degree of freedom) of zero slope for
continuous formaldehyde exposure among unexposed and exposed person-years;
parentheses indicate negative slope estimate.

Two-sided likelihood ratio test (1 degree of freedom) of zero slope for
continuous formaldehyde exposure among exposed person-years only;
parentheses indicate
negative slope estimate.
¶Exposure was calculated using a 2-year lag interval.
Table 2. Number of observed deaths and standardized mortality ratios (SMRs)
with 95% confidence intervals (CIs)

Cause of death (ICD codes?)
No. of observed deaths SMR (95% CI)
Unexposed Exposed Unexposed Exposed
All causes (001-999) 827 7659 0.77 (0.72 to 0.83) 0.95 (0.93 to 0.97)
All cancer (140-209) 183 1916 0.65 (0.56 to 0.75) 0.90 (0.86 to 0.94)
All solid malignant neoplasms (140-199) 166 1755 0.65 (0.56 to 0.76) 0.91
(0.87 to 0.96)
Lymphohematopoietic malignancies (200-209) 17 161 0.62 (0.39 to 1.00) 0.80
(0.69 to 0.94)
Non-Hodgkin's lymphoma (200, 202) 5 44 0.52 (0.22 to 1.25) 0.61 (0.46 to
0.83)
Hodgkin's disease (201) 1 20 0.37 (0.05 to 2.65) 1.26 (0.81 to 1.95)
Multiple myeloma (203) 5 28 1.23 (0.51 to 2.95) 0.88 (0.61 to 1.28)
Leukemia (204-207) 4 65 0.38 (0.14 to 1.00) 0.85 (0.67 to 1.09)
Benign neoplasms (210-239) 1 26 0.26 (0.04 to 1.87) 1.12 (0.76 to 1.64)
Circulatory system diseases (390-458) 371 3474 0.68 (0.62 to 0.76) 0.88
(0.85 to 0.91)
Respiratory diseases (460-519) 43 501 0.50 (0.37 to 0.67) 0.81 (0.74 to
0.89)
No. of person-years 135 396 730 312

Exposure status was calculated by using a 2-year lag interval.
?Codes of the International Classification of Diseases (ICD), 8th revision.

We found evidence of an association between Hodgkin's
disease (21 deaths) and exposure to formaldehyde. Compared
with workers exposed to low levels of formaldehyde (0.1-1.9
ppm peak exposure or 0.1-0.4 ppm average exposure intensity),
relative risks for Hodgkin's disease were 3.45 (95% CI 
 0.98
to 12.16) and 3.35 (95% CI 
 0.97 to 11.59) among workers
page 1618

Table 4. Relative risks for mortality from lymphohematopoietic malignancies
by average intensity of exposure to formaldehyde
Cause of death (ICD
)
Relative risk (95% confidence interval)?
Ptrend? Ptrend§
No. of deaths
Average intensity, ppm

0 0.1-0.4 0.5-0.9 
1.0
Lymphohematopoietic malignancies (200-209) 0.91 (0.52 to 1.59) 1.00
(Referent) 1.63 (1.11 to 2.37) 1.50 (1.01 to 2.24) .050 .062
17 81 42 38
Non-Hodgkin's lymphoma (200, 202) 1.02 (0.36 to 2.86) 1.00 (Referent) 1.33
(0.65 to 2.71) 0.98 (0.43 to 2.20) .690 .607
5 25 11 8
Hodgkin's disease (201) 0.46 (0.05 to 3.93) 1.00 (Referent) 4.70 (1.61 to
13.77) 3.12 (0.91 to 10.74) .022 .031
1 7 8 5
Multiple myeloma (203) 1.88 (0.62 to 5.65) 1.00 (Referent) 1.50 (0.60 to
3.74) 1.42 (0.56 to 3.58) (.855) (.801)
5 14 7 7
Leukemia (204-207) 0.56 (0.19 to 1.66) 1.00 (Referent) 1.52 (0.83 to 2.79)
1.68 (0.91 to 3.08) .193 .242
4 32 16 17
Lymphatic leukemia (204) 0.00 (0.00 to 2.02) 1.00 (Referent) 1.56 (0.52 to
4.65) 1.43 (0.47 to 4.34) .495 .632
0 9 5 5
Myeloid leukemia (205) 0.41 (0.08 to 1.95) 1.00 (Referent) 1.15 (0.41 to
3.23) 2.49 (1.03 to 6.03) .086 .088
2 14 5 9
Other/unspecified leukemia (207) 1.27 (0.25 to 6.40) 1.00 (Referent) 1.69
(0.56 to 5.12) 0.98 (0.26 to 3.71) (.697) (.710)
2 9 5 3
No. of person-years 135 396 454 927 139 628 135 757

Codes of the International Classification of Diseases (ICD), 8th revision.
?Relative risks were derived from Poisson regression stratified for calendar
year, age (both in 5-year intervals), sex, and race/ethnicity (black/white),
and adjusted
for pay category (salary/wage). Cut points for formaldehyde exposure
categories were approximately the 60th and 80th percentiles of the
distribution of the respective
exposure measure in exposed subjects who died from cancer. These cut points
ensured that there were sufficient numbers of cases in the exposed
categories.
?Two-sided likelihood ratio test (1 degree of freedom) of zero slope for
continuous formaldehyde exposure among unexposed and exposed person-years;
parentheses indicate negative slope estimate.
§Two-sided likelihood ratio test (1 degree of freedom) of zero slope for
continuous formaldehyde exposure among exposed person-years only;
parentheses indicate
negative slope estimate.

Exposure was calculated using a 2-year lag interval.

Table 5. Relative risks for mortality from lymphohematopoietic malignancies
by cumulative exposure to formaldehyde
Cause of death (ICD
)
Relative risk (95% confidence intervals)?
Ptrend? Ptrend§
No. of deaths
Cumulative exposure, ppm-years

0 0.1-1.4 1.5-5.4 
5.5
Lymphohematopoietic malignancies (200-209) 0.74 (0.42 to 1.30) 1.00
(Referent) 0.79 (0.52 to 1.21) 1.03 (0.70 to 1.52) .157 .202
17 94 29 38
Non-Hodgkin's lymphoma (200, 202) 0.82 (0.29 to 2.34) 1.00 (Referent) 0.53
(0.22 to 1.31) 0.92 (0.45 to 1.88) .968 .969
5 27 6 11
Hodgkin's disease (201) 0.29 (0.04 to 2.34) 1.00 (Referent) 1.35 (0.45 to
3.99) 1.17 (0.31 to 4.46) .037 .045
1 12 5 3
Multiple myeloma (203) 1.49 (0.50 to 4.46) 1.00 (Referent) 0.62 (0.21 to
1.85) 1.03 (0.42 to 2.52) (.877) (.899)
5 17 4 7
Leukemia (204-207) 0.48 (0.16 to 1.42) 1.00 (Referent) 0.90 (0.47 to 1.73)
1.14 (0.63 to 2.07) .183 .235
4 35 13 17
Lymphatic leukemia (204) 0.00 (0.00 to 1.67) 1.00 (Referent) 0.72 (0.20 to
2.63) 1.20 (0.43 to 3.33) .406 .476
0 10 3 6
Myeloid leukemia (205) 0.32 (0.07 to 1.51) 1.00 (Referent) 0.57 (0.19 to
1.73) 1.02 (0.40 to 2.55) .123 .157
2 17 4 7
Other/unspecified leukemia (207) 1.37 (0.26 to 7.20) 1.00 (Referent) 1.60
(0.51 to 5.01) 1.28 (0.38 to 4.36) (.740) (.783)
2 8 5 4
No. of person-years 135 396 494 579 135 240 100 493

Codes of the International Classification of Diseases (ICD), 8th revision.
?Relative risks were derived from Poisson regression stratified for calendar
year, age (both in 5-year intervals), sex, and race/ethnicity (black/white),
and adjusted
for pay category (salary/wage). Cut points for formaldehyde exposure
categories were approximately the 60th and 80th percentiles of the
distribution of the respective
exposure measure in exposed subjects who died from cancer. These cut points
ensured that there were sufficient numbers of cases in the exposed
categories.
?Two-sided likelihood ratio test (1 degree of freedom) of zero slope for
continuous formaldehyde exposure among unexposed and exposed person-years;
parentheses indicate negative slope estimate.
§Two-sided likelihood ratio test (1 degree of freedom) of zero slope for
continuous formaldehyde exposure among exposed person-years only;
parentheses indicate
negative slope estimate.

Exposure was calculated using a 2-year lag interval.

exposed to formaldehyde at 2.0-3.9 ppm and 
4.0 ppm peak
exposure, respectively (Ptrend 
 .042), and 4.70 (95% CI 
 1.61
to 13.77) and 3.12 (95% CI 
 0.91 to 10.74) for workers
exposed at 0.5-0.9 ppm and 
1.0 ppm average exposure intensity,
respectively (Ptrend 
 .031) (Tables 3 and 4). A trend was
also observed for cumulative exposure (Ptrend 
 .045) (Table 5).
Neither non-Hodgkin's lymphoma nor multiple myeloma was
associated with any of the formaldehyde exposure measures
(Tables 3-6).

Because information on exposure ended in 1980, exposure
may have been underestimated for some subjects who were
exposed after 1980. However, the underestimate would be small
because only 3.7% of all person-years were contributed by
workers aged 65 years or younger and in exposed jobs in 1980.
When those person-years were excluded from the analysis, the
results did not change.

Potential Confounding by Exposure to Substances Other
Than Formaldehyde
Forty-seven percent of the cohort members were ever exposed
in the workplace to at least one of the following substances:
antioxidants (22%), asbestos (14%), carbon black
(11%), dyes and pigments (16%), hexamethylenetetramine
(15%), melamine (28%), phenol (14%), plasticizers (20%), urea
(27%), wood dust (10%), and benzene (2%). Of those ever
exposed to benzene, there were six deaths from lymphohematopoietic
malignancies, including one from myeloid leukemia.
Only 8% of the cohort ever worked as chemists or laboratory
technicians, and only 2% worked in such jobs for 5 or more
years. Duration of exposure to dyes and pigments, melamine,
and plasticizers was associated with all leukemia mortality (data
not shown). Working as a chemist or laboratory technician was
also associated with leukemia mortality (data not shown). The
small numbers precluded a detailed evaluation of associations
with benzene.

Relative risk estimates for myeloid leukemia, all leukemias,
and all lymphohematopoietic malignancies did not change substantially,
compared with the unadjusted analysis, when analyses
were adjusted for duration of exposure to each of the 10 other
substances and for working as a chemist or laboratory technician.
We also repeated all analyses excluding the 586 subjects
exposed to benzene and found no substantial differences between
those results and the results of the analysis including all
subjects.

Peak exposure and average exposure intensity were not evaluated
in the previous analysis of this cohort (7). We evaluated
the earlier data for associations with these exposure measures by
limiting the analysis to follow-up through 1980, and found that
relative risks for leukemia (25 deaths) and the exposure categories
shown in Tables 3 and 4 for peak exposure were 1.00, 1.00,
1.68, and 1.49 (Ptrend 
 .423) and for average intensity were
0.89, 1.00, 1.50, and 1.35 (Ptrend 
 .863). Increased relative risks
for medium- and high-exposure categories show that there was
some indication of an association in the earlier follow-up.

DISCUSSION
We observed an association between mortality from leukemia,
particularly for myeloid leukemia, and several indices of
potential exposure to formaldehyde among industrial workers.
page 1619

Table 6. Relative risks for mortality from lymphohematopoietic malignancies
by duration of exposure to formaldehyde
Cause of death (ICD*)
Relative risk (95% confidence interval)?
Ptrend? Ptrend§
No. of deaths
Duration of exposure, y

0 0.1-4.9 5.0-14.9 
15.0
Lymphohematopoietic malignancies (200-209) 0.75 (0.42 to 1.31) 1.00
(Referent) 0.74 (0.47 to 1.18) 1.07 (0.73 to 1.55) .905 (.752)
17 90 24 47
Non-Hodgkin's lymphoma (200, 202) 0.86 (0.29 to 2.49) 1.00 (Referent) 0.56
(0.21 to 1.49) 0.98 (0.49 to 1.96) (.613) (.512)
5 25 5 14
Hodgkin's disease (201) 0.23 (0.03 to 1.85) 1.00 (Referent) 0.77 (0.24 to
2.45) 0.59 (0.12 to 2.93) (.799) (.422)
1 14 4 2
Multiple myeloma (203) 1.44 (0.48 to 4.35) 1.00 (Referent) 0.36 (0.08 to
1.57) 1.05 (0.45 to 2.43) (.706) .980
5 17 2 9
Leukemia (204-207) 0.55 (0.18 to 1.66) 1.00 (Referent) 1.16 (0.59 to 2.26)
1.39 (0.78 to 2.49) .214 .465
4 30 13 22
Lymphatic leukemia (204) 0.00 (0.00 to 2.51) 1.00 (Referent) 1.87 (0.58 to
6.05) 1.62 (0.55 to 4.74) .498 .684
0 7 5 7
Myeloid leukemia (205) 0.34 (0.07 to 1.67) 1.00 (Referent) 0.49 (0.14 to
1.73) 1.35 (0.56 to 3.24) .423 .911
2 15 3 10
Other/unspecified leukemia (207) 1.36 (0.25 to 7.23) 1.00 (Referent) 1.49
(0.44 to 5.09) 1.30 (0.41 to 4.13) .402 .292
2 8 4 5
No. of person-years 135 396 498 167 134 963 97 182

Codes of the International Classification of Diseases (ICD), 8th revision.
?Relative risks were derived from Poisson regression stratified for calendar
year, age (both in 5-year intervals), sex, and race/ethnicity (black/white),
and adjusted
for pay category (salary/wage). Cut points for formaldehyde exposure
categories were approximately the 60th and 80th percentiles of the
distribution of the respective
exposure measure in exposed subjects who died from cancer. These cut points
ensured that there were sufficient numbers of cases in the exposed
categories.
?Two-sided likelihood ratio test (1 degree of freedom) of zero slope for
continuous formaldehyde exposure among unexposed and exposed person-years;
parentheses indicate negative slope estimate.
§Two-sided likelihood ratio test (1 degree of freedom) of zero slope for
continuous formaldehyde exposure among exposed person-years only;
parentheses indicate
negative slope estimate.

Exposure was calculated using a 2-year lag interval.
page 1620

On the basis of our results and those previously reporting more
leukemia than expected among professional workers exposed to
formaldehyde (14), it appears that formaldehyde may cause
leukemia in humans. The association found between Hodgkin's
disease and formaldehyde exposure is more difficult to interpret
because it has not been observed previously.

Increased SMRs and relative risks for lymphohematopoietic
malignancies have been reported in several studies of professionals
exposed to formaldehyde (14-19) and occasionally
among industrial workers (14,20). In several of these studies, the
excess of leukemia was mainly due to myeloid leukemia (16-
19), a finding that also emerged from our data.

Our findings can be compared with recent results from extended
follow-ups of two other cohort studies of formaldehydeexposed
workers. Among 14,014 men employed in the British
formaldehyde industry, there were fewer deaths than expected
from leukemia overall (31 deaths observed versus 34.1 deaths
expected) and among workers in high-exposure jobs (eight
deaths observed versus 11.3 deaths expected) (21). The study by
Coggon et al. (21) was similar to ours in that it included
quantitative estimates of formaldehyde exposure from production
of urea and melamine formaldehyde resins, but it differed
from ours in that peak exposure and average exposure intensity
were not evaluated and in that our study had more than twice the
number of deaths from leukemia. In a National Institute for
Occupational Safety and Health cohort study of 11,039 textile
workers with potential exposure to formaldehyde, researchers
found an increase in leukemia mortality with longer duration of
employment, i.e., SMRs (number of deaths) 
 0.96 (seven),
0.72 (five), and 1.53 (12) for 3, 3-9, and 
10 years, respectively
(22). The increase in SMR with duration of employment
was similar to the increasing relative risks associated with duration
of exposure in our study.

Experimental evidence regarding the effects of formaldehyde
at sites other than the upper respiratory tract is inconsistent.
Some biologic evidence suggests that carcinogenic effects of
formaldehyde at non-upper respiratory tract sites would be
unlikely. For example, nearly the total inhaled dose of formaldehyde
is deposited in the upper respiratory tract after long-term
inhalation in rats (23), blood levels of formaldehyde did not
change after inhalation exposure to formaldehyde in rats or
humans (24), and, after rats inhaled radioactively labeled formaldehyde,
substantial concentrations of radioactivity were localized
in bone marrow DNA, but there was no indication that
inhaled formaldehyde formed adducts or cross-links with bone
marrow macromolecules (25).

However, other experimental evidence supports the epidemiologic
findings by suggesting that formaldehyde is associated
with toxicity at sites remote from the respiratory tract. For
example, increased frequencies of micronuclei (26-28), sister
chromatid exchanges (28-31), chromosomal aberrations (28,32),
and DNA-protein cross-links (6,30) have been found in peripheral
lymphocytes of humans exposed to formaldehyde. Other
studies (33-37) found some of these anomalies. Although there
is a clear link between chromosomal aberrations and cancer (38),
the relationships between micronuclei or sister chromatid exchanges
and health risks are not well documented (39). In rats,
long-term inhalation of formaldehyde vapor at low concentrations
of 0.6 and 1.8 ppm was associated with dose-related bone
marrow cytotoxicity, including chromosomal aberrations and
aneuploidy (40), although short-term exposure to formaldehyde
at high concentrations of 15 ppm was not (41). A statistically
significant dose-related increase in leukemia incidence was observed
in Sprague-Dawley rats administered 10-1500 ppm
formaldehyde in drinking water for 2 years (42), but not in
Wistar rats (43,44). It appears that formaldehyde-induced mutagenesis
involves mainly small-scale chromosomal rearrangements
rather than point mutations (45). Small-scale chromosomal
rearrangements are reminiscent of karyotypic anomalies
found in the hematopoietic stem cells of many patients with
lymphohematopoietic malignancies (46). Hematopoietic stem
cells are found in the bone marrow and in the peripheral blood.
In peripheral blood, they could be exposed to the potentially
toxic effects of formaldehyde, although the clinical significance
of such exposures in leukemogenesis is unclear.

In this study, leukemia was associated with peak exposure to
formaldehyde and, to a lesser degree, average exposure intensity
and duration of exposure, but not with cumulative exposure.
Multiple measures of exposure can complicate the interpretation
of results when the measure that best characterizes delivered
dose is unknown, as with formaldehyde. The initial interpretation
of the results focused on whether any of the measures of
formaldehyde exposure was associated with leukemia. By using
four exposure measures rather than only one, we substantially
reduced the risk of an overall false-negative finding. Although
using four measures increased the chance of a false-positive
result for a single exposure measure, we limited the possibility
of a false-positive error for each measure by evaluating several
aspects of a potential exposure-response relationship (i.e., increasing
relative risks with categories of exposure, statistically
significantly elevated relative risks, and statistically significant
trends). We then interpreted the pattern of the exposure measures
for which an association was or was not found. Observing
generally weaker or no associations for duration of exposure
than for metrics of intensity, e.g., average exposure intensity or
peak exposure, was not surprising because duration as a measure
of exposure assumes a constant exposure rate for all jobs and
over time, which does not hold in this study. Therefore, the use
of duration of exposure to evaluate associations results in substantial
exposure misclassification. However, the absence of an
association between cumulative exposure and leukemia given
the associations with the other three exposure measures was
unexpected.

Risk estimates could be confounded by other occupational
exposures. However, our findings of the association between
formaldehyde exposure and leukemia are not explained by exposure
to 11 other agents used in these industrial plants or by
working as a chemist or laboratory technician. We were concerned
about benzene, a known risk factor for leukemia, and
found no difference in the results when all workers exposed to
benzene were excluded from the analyses. Although tobacco
exposure has been weakly linked with leukemia (47), it is
unlikely to explain our findings because there was no consistent
increase in tobacco-related diseases, including lung cancer,
among the cohort. Information on smoking from medical records
for a sample of 63 workers with cancer and 316 age-matched
control subjects from two plants revealed no major differences
in smoking prevalence by level of exposure to formaldehyde (8).
Analyses were not adjusted for plant for two reasons. First, we
directly addressed confounding by factors potentially associated
with plant by adjusting for 11 potentially confounding substances.
Second, adjusting for plant may potentially result in
page 1621

overadjustment. However, to address the potential effect of
unmeasured confounders associated with plant, we performed
analyses adjusted for plant and separately by plant type (resins,
four plants; plywood, one plant; film, two plants; formaldehyde
and resins, three plants). Although some of these analyses were
based on small numbers and, as a consequence, estimates had
large variances, associations for leukemia and Hodgkin's disease
found in the adjusted analyses were similar to those in the
analyses that did not adjust for plant.

One potential limitation of our study was exposure misclassification.
The detailed approach to developing quantitative estimates
of time-weighted average exposure intensity by using
monitoring data provided by the companies, monitoring in each
plant by study investigators (13), having study industrial hygienists
visit the plants, and discussing exposure with plant managers
and long-time workers (9) should have minimized misclassifi-
cation of average and cumulative exposure and of duration of
exposure. The assessment of peak exposure could have been
more susceptible to misclassification because peak levels were
estimated from time-weighted average exposure and job tasks.
However, any exposure misclassification should be nondifferential
with respect to disease status in a cohort study, in which
exposure is assessed before disease outcome, and this nondifferential
exposure misclassification would attenuate exposure-
response patterns. Moreover, associations with peak exposure
changed little when peak exposures in jobs of short duration (1
year) and when peak exposures that occurred less often than
daily were excluded from the analyses. Therefore, exposure
misclassification is unlikely to be responsible for the positive
findings in our study.

A second potential limitation was the lack of information on
exposures during the recent follow-up (1980-1994), which
could cause an underestimation of exposure for individuals
working after 1980. However, the impact would be minimal
because only a small proportion of individuals was likely exposed
after 1980 (3.7% of all person-years) and, for those
workers, levels of exposure were probably considerably lower
after 1980 than in earlier years. Although the accuracy of death
certificates for lymphohematopoietic malignancies is generally
high, classification of subtypes of leukemia and lymphoma from
death certificates is less accurate than classification from hospital
records (48). However, in this study, any disease misclassi-
fication should be nondifferential with respect to formaldehyde
exposure. In our follow-up, individuals not identified as deceased
by the National Death Index Plus were assumed to be
alive. Although a violation of this assumption could result in
some underascertainment of deaths, underascertainment is unlikely
to be related to formaldehyde exposure and, therefore,
should not have biased the results.

Our study has several major strengths, including its large size
(up to 60 years of follow-up and 178 deaths from lymphohematopoietic
malignancies) and the extensive assessment of formaldehyde
exposure by using several measures (peak, average,
cumulative, and duration of exposure). Because these measures
were only moderately correlated (10), they classify workers
differently and provide relatively independent assessments of
exposure-response. Duration of exposure to formaldehyde was
poorly correlated with peak exposure or average intensity [Pearson
correlation coefficients were 0.3 and 0.0, respectively (10)],
which may explain its lack of association with leukemia. In
addition, we did not rely on external comparisons (i.e., SMRs),
which are subject to a healthy worker bias (49), but instead
focused on internal analyses that compared similar individuals.

In summary, the increased risk for leukemia mortality, particularly
myeloid leukemia, from peak and average exposure to
formaldehyde could not be explained by obvious biases or
confounding. The exposure-response gradient observed and the
consistency with other epidemiologic studies of workers in occupations
with formaldehyde exposure and some experimental
studies suggest a causal association between formaldehyde exposure
and leukemia. However, lack of an association in a recent
follow-up of a similar but smaller industrial cohort in Great
Britain (21) introduces uncertainty regarding the relationship.

REFERENCES
(1) Smith R. Environmental economics and the new paradigm. Chemical
Industry Newsletter, Nov.-Dec., 8, 1993.
(2) United States National Institute of Occupational Safety and Health.
National
occupational exposure survey 1981-83. Cincinnati (OH). 1990.
(3) International Agency for Research on Cancer (IARC). IARC monographs
on the evaluation of carcinogenic risks to humans. Vol. 62. Wood dust and
formaldehyde. Lyon (France): IARC; 1995.
(4) Kerns WD, Pavkov KL, Donofrio DJ, Gralla EJ, Swenberg JA.
Carcinogenicity
of formaldehyde in rats and mice after long-term inhalation exposure.
Cancer Res 1983;43:4382-92.
(5) Sellakumar AR, Snyder CA, Solomon JJ, Albert RE. Carcinogenicity of
formaldehyde and hydrogen chloride in rats. Toxicol Appl Pharmacol
1985;81:401-6.
(6) Shaham J, Bomstein Y, Meltzer A, Kaufman Z, Palma E, Ribak J. DNA-
protein crosslinks, a biomarker of exposure to formaldehyde-in vitro and in
vivo studies. Carcinogenesis 1996;17:121-5.
(7) Blair A, Stewart P, O'Berg M, Gaffey W, Walrath J, Ward J, et al.
Mortality among industrial workers exposed to formaldehyde. J Natl Cancer
Inst 1986;76:1071-84.
(8) Blair A, Stewart PA, Hoover RN. Mortality from lung cancer among
workers employed in formaldehyde industries. Am J Ind Med 1990;17:
683-99.
(9) Stewart PA, Blair A, Cubit DA, Bales RE, Kaplan SA, Ward J, et al.
Estimating historical exposure to formaldehyde in a retrospective mortality
study. Appl Ind Hyg 1986;1:34-41.
(10) Blair A, Stewart PA. Correlation between different measures of
occupational
exposure to formaldehyde. Am J Epidemiol 1990;13:510-6.
(11) Breslow NE, Day NE. Statistical methods in cancer research. Volume
II-The design and analysis of cohort studies. IARC Sci Publ 1987;(82):1-
406.
(12) Preston DL, Lubin JH, Pierce DA, McConney ME. Epicure release 2.0.
Seattle (WA): HiroSoft International; 1996.
(13) Stewart PA, Cubit D, Blair A. Formaldehyde levels in seven industries.
Appl Ind Hyg 1987;2:231-6.
(14) Blair A, Saracci R, Stewart PA, Hayes RB, Shy C. Epidemiologic evidence
on the relationship between formaldehyde exposure and cancer. Scand J
Work Environ Health 1990;16:381-93.
(15) Harrington JM, Shannon HS. Mortality study of pathologists and medical
laboratory technicians. Br Med J 1975;4:329-32.
(16) Walrath J, Fraumeni JF Jr. Mortality patterns among embalmers. Int J
Cancer 1983;31:407-11.
(17) Walrath J, Fraumeni JF Jr. Cancer and other causes of death among
embalmers. Cancer Res 1984;44:4638-41.
(18) Stroup NE, Blair A, Erikson GE. Brain cancer and other causes of death
in
anatomists. J Natl Cancer Inst 1986;77:1217-24.
(19) Hayes RB, Blair A, Stewart PA, Herrick RF, Mahar H. Mortality of U.S.
embalmers and funeral directors. Am J Ind Med 1990;18:641-52.
(20) Bertazzi PA, Pesatori AC, Radice L, Zocchetti C, Vai T. Exposure to
formaldehyde and cancer mortality in a cohort of workers producing resins.
Scand J Work Environ Health 1986;12:461-8.
(21) Coggon D, Harris EC, Poole J, Palmer KT. Extended follow-up of a cohort
of British chemical workers exposed to formaldehyde. J Natl Cancer Inst
2003;95:1608-15.
page 1622

(22) Pinkerton LE, Hein MJ, Stayner LT. Mortality among a cohort of garment
workers exposed to formaldehyde: an update. Occup Environ Med. In press
2003.
(23) Dallas CE, Theiss JC, Harrist RB, Fairchild EJ. Effect of subchronic
formaldehyde inhalation on minute volume and nasal deposition in
Sprague-Dawley rats. J Toxicol Environ Health 1985;16:553-64.
(24) Heck HD, Casanova-Schmitz M, Dodd PB, Schachter EN, Witek TJ, Tosun
T. Formaldehyde (CH2O) concentrations in the blood of humans and
Fischer-344 rats exposed to CH2O under controlled conditions. Am Ind
Hyg Assoc J 1985;46:1-3.
(25) Casanova-Schmitz M, Starr TB, Heck HD. Differentiation between
metabolic
incorporation and covalent binding in the labeling of macromolecules
in the rat nasal mucosa and bone marrow by inhaled [14C]- and
[3H]formaldehyde.
Toxicol Appl Pharmacol 1984;76:26-44.
(26) Kitaeva LV, Mikheeva EA, Shelomova LF, Shvartsman PI. Genotoxic
effect of formaldehyde in somatic human cells in vivo. Genetika 1996;32:
1287-90.
(27) Suruda A, Schulte P, Boeniger M, Hayes RB, Livingston GK, Steenland K,
et al. Cytogenetic effects of formaldehyde exposure in students of mortuary
science. Cancer Epidemiol Biomarkers Prev 1993;2:453-60.
(28) He JL, Jin LF, Jin HY. Detection of cytogenetic effects in peripheral
lymphocytes of students exposed to formaldehyde with cytokinesisblocked
micronucleus assay. Biomed Environ Sci 1998;11:87-92.
(29) Yager JW, Cohn KL, Spear RC, Fisher JM, Morse L. Sister-chromatid
exchanges in lymphocytes of anatomy students exposed to
formaldehydeembalming
solution. Mutat Res 1986;174:135-9.
(30) Shaham J, Bomstein Y, Meltzer A, Ribak J. DNA-protein crosslinks and
sister chromatid exchanges as biomarkers of exposure to formaldehyde. Int
J Occup Environ Health 1997;3:95-104.
(31) Shaham J, Gurvich R, Kaufman Z. Sister chromatid exchange in pathology
staff occupationally exposed to formaldehyde. Mutat Res 2002;15:115-23.
(32) Bauchinger M, Schmid E. Cytogenetic effects in lymphocytes of
formaldehyde
workers of a paper factory. Mutat Res 1985;158:195-9.
(33) Ying CJ, Yan WS, Zhao MY, Ye XL, Xie H, Yin SY, et al. Micronuclei in
nasal mucosa, oral mucosa and lymphocytes in students exposed to
formaldehyde
vapor in anatomy class. Biomed Environ Sci 1997;10:451-5.
(34) Ying CJ, Ye XL, Xie H, Yan WS, Zhao MY, Xia T, et al. Lymphocyte
subsets and sister-chromatid exchanges in the students exposed to
formaldehyde
vapor. Biomed Environ Sci 1999;12:88-94.
(35) Thomson EJ, Shackleton S, Harrington JM. Chromosome aberrations and
sister-chromatid exchange frequencies in pathology staff occupationally
exposed to formaldehyde. Mutat Res 1984;141:89-93.
(36) Vasudeva N, Anand C. Cytogenetic evaluation of medical students exposed
to formaldehyde vapor in the gross anatomy dissection laboratory. J Am
Coll Health 1996;44:177-9.
(37) Fleig I, Petri N, Stocker WG, Thiess AM. Cytogenetic analyses of blood
lymphocytes of workers exposed to formaldehyde in formaldehyde manufacturing
and processing. J Occup Med 1982;24:1009-12.
(38) Bonassi S, Hagmar L, Stromberg U, Montagud AH, Tinnerberg H, Forni A,
et al. Chromosomal aberrations in lymphocytes predict human cancer
independently of exposure to carcinogens. European Study Group on
Cytogenetic Biomarkers and Health. Cancer Res 2000;60:1619-25.
(39) Tucker JD, Preston RJ. Chromosome aberrations, micronuclei, aneuploidy,
sister chromatid exchanges, and cancer risk assessment. Mutat Res 1996;
365:147-59.
(40) Kitaeva LV, Kitaev EM, Pimenova MN. The cytopathic and cytogenetic
sequelae of chronic inhalational exposure to formaldehyde on female germ
cells and bone marrow cells in rats. Tsitologiia 1990;32:1212-6.
(41) Dallas CE, Scott MJ, Ward JB Jr, Theiss JC. Cytogenetic analysis of
pulmonary lavage and bone marrow cells of rats after repeated formaldehyde
inhalation. J Appl Toxicol 1992;12:199-203.
(42) Soffritti M, Maffei F, Biagi R. Formaldehyde: an experimental
multipotential
carcinogen. Toxicol Ind Health 1989;5:699-730.
(43) Til HP, Woutersen RA, Feron VJ, Hollanders VH, Falke HE, Clary JJ.
Two-year drinking-water study of formaldehyde in rats. Food Chem Toxicol
1989;27:77-87.
(44) Tobe M, Naito K, Kurokawa Y. Chronic toxicity study on formaldehyde
administered orally to rats. Toxicology 1989;56:79-86.
(45) Speit G, Merk O. Evaluation of mutagenic effects of formaldehyde in
vitro:
detection of crosslinks and mutations in mouse lymphoma cells. Mutagenesis
2002;17:183-7.
(46) Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and
cancer stem cells. Nature 2001;414:105-11.
(47) Linet MS, Cartwright RA. The leukemias. In: Schottenfeld D, Fraumeni JF
Jr, editors. Cancer epidemiology and prevention. 2nd ed. New York (NY):
Oxford University Press; 1996. p. 841-92.
(48) Percy C, Stanek E III, Gloeckler L. Accuracy of cancer death
certificates
and its effect on cancer mortality statistics. Am J Public Health 1981;71:
242-50.
(49) Fox A, Collier PF. Low mortality rates in industrial cohort studies due
to
selection for work and survival in the industry. Br J Prev Soc Med
1976;30:225-30.

NOTES
Funded by the National Cancer Institute, National Institutes of Health,
Department
of Health and Human Services.
We thank Drs. Elizabeth Fontham, David Savitz, Michael Thun, and Robert
Hoover for review and helpful suggestions. We shared the manuscript with
participating companies and unions and appreciate their comments.
Manuscript received April 4, 2003; revised August 29, 2003; accepted
September 11, 2003.
page 1623
*******************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1053 posts in a public searchable archive  125 members

http://groups.yahoo.com/group/aspartame/messages 759 with 16,425 posts

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L (becomes
formaldehyde in body):
EU Scientific Committee on Foods 7.12.1: Murray 1.22.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M  ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo.  Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male)  alemany@...

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ].  Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@...    919-684-3303, 660-5657
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall ]

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame (12.4.2): 59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall  EU Scientific Committee on Food, a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1018
aspartame toxicity coverup increases danger of corporate meltdown:
Michael C. Carakostas of Coca-Cola: Murray 8.11.3 rmforall
http://www.isrtp.org/new_members/members1.htm
The International Society of Regulatory Toxicology and Pharmacology
Carakostas, Michael C., DVM, PhD Director/Scientific & Regulatory
Affairs   The Coca-Cola Company PO Drawer 1734 Atlanta, GA 30301
T. 404/676-4234   F. 404/676-7166   E-mail: mcarakostas@...
http://www2.coca-cola.com/ourcompany/columns_aspartame.html  [photo]
Aspartame: The world agrees it's safe   By Michael Carakostas, DVM, PhD
Director, Scientific and Regulatory Affairs, Coca-Cola

It is commendable that Carakostas mentions the core problem, albeit
disparagingly:   "During digestion, aspartame yields a very small amount
of methanol-- as do many other food substances. The body converts this
methanol to formaldehyde, which is instantly converted to formate.
Formate is quickly eliminated as carbon dioxide and water."

Plenty of evidence in the mainstream scientific literature since 1973
shows that as much as 30% of the formaldehyde is retained in the body as
toxic, cumulative adducts to the DNA, RNA, and proteins in all cells and
tissues, leading to pointed reports by informed doctors and experts.
Clearly, there are no safe levels for chronic, low-level formaldehyde
exposure.  If just 10% of the methanol from six cans of diet soda is
retained in the body as toxic products of formaldehyde and formic acid,
that is sixty times the EPA limit for allowable formaldehyde from daily
drinking water.

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Formaldehyde was administered for 104 weeks in drinking water supplied
ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
rats beginning at six weeks of age at concentrations of 2,500, 1,500,
500, 250, 50, or 0 mg/L.
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase in total
malignant tumors in the treated groups and showed specific carcinogenic
effects on various organs and tissues.  PMID: 12562630

Surely the authors deliberately emphasized that aspartame is well-known
to be a source of formaldehyde, which is an extremely potent, cumulative
toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested
aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No.      No. of Bioassays  Species    No.       Route of Exposure
108.  "Coca-Cola"     4     Rat       1,999    Ingestion, Transplantal Route
109.  "Pepsi-Cola"    1      Rat          400         Ingestion
110.   Sucrose          1      Rat          400         Ingestion
111.   Caffeine          1      Rat          800         Ingestion
112.   Aspartame      1      Rat       1,800         Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]

http://www.dorway.com/tldaddic.html  5-page review
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter  2000 Jan;  HJRobertsMD@...
http://www.sunsentpress.com/    sunsentpress@...
Sunshine Sentinel Press  P.O.Box 17799  West Palm Beach, FL 33416
800-814-9800 561-588-7628 561-547-8008 fax

http://groups.yahoo.com/group/aspartameNM/message/669
1038-page medical text   "Aspartame Disease: An Ignored Epidemic"
published May 30  2001    $ 60.00 postpaid    data from 1200 cases
available at  http://www.amazon.com
over 600 references from standard medical research
*******************************************************************

http://groups.yahoo.com/group/aspartameNM/message/189
Epstein: The Politics of Cancer Revisited 1998  3.6.00

Subject: From Dr. Epstein
     Date: Mon, 06 Mar 2000 10:20:08 -0600
    From: "Samuel S. Epstein, M.D" <epstein@...>
        To:  Rich Murray <rmforall@...>

March 6, 2000

Dear Rich:

Thank you for your recent emails which I think make a very useful
contribution.  Your comments on Jensen's recent article are also
appreciated.

With reference to HGH/IGF-1, you may be unaware that I have published
extensively in these areas since 1989.  You will find some material on
my website,  www.preventcancer.com  and much more detail in Appendix
XII of my 1998 book "The Politics of Cancer Revisited", East Ridge
Press, Fremont Center, New York, 1998: N.Y. email:  eastridge@...
800-269-2921: USA, Fax: 914-887-5982, 914-887-6467.  Besides also
dealing in great detail with causes of prevention of a wide range of
avoidable cancers, the book analyzes the culpability of the cancer
establishment -- the National Cancer Institute and American Cancer
Society -- in losing the winnable war against cancer.
Keep up the good work.

Samuel S. Epstein, M.D.
*********************************************************************

The Sun, 107 North Roberson Street, Chapel Hill, NC 27516  919-942-5282
The Sun, March 2000, (291) p. 4--13, An Epidemic of Deception: why we
can't trust the cancer establishment: an interview with Samuel Epstein
by Derrick Jensen [ Crescent City, CA   dbjensen1@...
www.wave.net/tsn/djensen/unpub.htm ]

A Language Older Than Words [newest book, now at Context Books]
***********************************************************************

http://www.preventcancer.com/    Cancer Prevention Coalition

On The twentieth anniversary of the "War Against Cancer," an ad hoc
group of 60 prominent public health experts and scientists, launched a
public education campaign to reform national cancer policies.  The
scientists cited statistics that showed the incidence of cancer has
increased sharply, while cancer treatment has not materially improved
for decades. The group also claimed that the causal role of avoidable
exposures to industrial carcinogens in air, water, food, consumer
products and the work place have been trivialized for decades. This
was the impetus that led to the forming of the Cancer Prevention
Coalition (CPC).  Since its inception in 1994, CPC has become one of
the leading groups of the independent experts on cancer prevention and
public health, with citizen activists, organized labor, public interest
and women's cancer groups.  Chairman: Samuel S. Epstein, PhD
Cancer Prevention Coalition c/o School of Public Health
University of Illinois Medical Center
2121 West Taylor Street Chicago, IL 60612
TEL(312) 996-2297, FAX(312) 996-1374   Email: epstein@...

Int J Health Serv 1999; 29(3): 565-78.
American Cancer Society: the world's wealthiest "nonprofit"
institution.
Epstein SS
School of Public Health, University of Illinois at Chicago
60612-7260, USA.

The American Cancer Society is fixated on damage control-- diagnosis and
treatment-- and basic molecular biology, with indifference or even
hostility to cancer prevention. This myopic mindset is compounded by
interlocking conflicts of interest with the cancer drug, mammography,
and other industries. The "nonprofit" status of the Society is in sharp
conflict with its high overhead and expenses, excessive reserves of
assets and contributions to political parties. All attempts to reform
the Society over the past two decades have failed; a national economic
boycott of the Society is long overdue. PMID: 10450547, UI: 99379041

Int J Health Serv 1996; 26(1): 173-85.
Unlabeled milk from cows treated with biosynthetic growth hormones: a
case of regulatory abdication.
Epstein SS
School of Public Health West, University of Illinois
Chicago 60612, USA.

Levels of insulin-like growth factor-1 (IGF-1) are substantially
elevated and more bioactive in the milk of cows hyperstimulated with
the biosynthetic bovine growth hormones rBGH, and are further
increased by pasteurization. IGF-1 is absorbed from the
gastrointestinal tract, as evidenced by marked growth-promoting
effects even in short-term tests in mature rats, and absorption is
likely to be still higher in infants. Converging lines of evidence
incriminate IGF-1 in rBGH milk as a potential risk factor for both
breast and gastrointestinal cancers.  PMID: 8932606, UI: 97086412

Int J Health Serv 1994; 24(1): 145-50.
Environmental and occupational pollutants are avoidable causes of
breast cancer.
Epstein SS
School of Public Health West, University of Illinois Medical Center at
Chicago 60612.

For over three decades, evidence has accumulated relating avoidable
exposures to environmental and occupational carcinogens to the
escalating incidence of breast cancer in the United States and other
major industrialized nations. This evidence has until very recently
been totally ignored by the cancer establishment, the National Cancer
Institute, and the American Cancer Society, despite expenditures of
over $1 billion on breast cancer research. Recognition of these
environmental and occupational risk factors should lead to the belated
development of public health policies directed to the primary prevention
of breast cancer. Their recognition should also lend urgency to the need for
radical reforms in the priorities and leadership of the cancer
establishment.
PMID: 8150563, UI: 94200917
***********************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L (becomes
formaldehyde in body):
EU Scientific Committee on Foods 7.12.1: Murray 1.22.4 rmforall

"...DMDC was evaluated by the SCF in 1990 and considered acceptable for the cold
sterilization of soft drinks and fruit juices at levels of addition up to 250
mg/L (1)
...DMDC decomposes primarily to CO2 and methanol ...

The use of 200 mg DMDC/L would add 98 mg/L of methanol to wine which already
contains an average of about 140 mg/L from natural sources. A healthy person
metabolises 1500 mg methanol/hr without any physiological problems and this
should be compared to the amount of up to 240 mg/L methanol in wine, treated
with DMDC up to 200 mg/L. Metabolism of the amounts of methanol resulting
from consumption of wine containing such levels is therefore well within the
capacity of the human body. Thus consumption of even large quantities of
wine would not pose any hazards from methanol.

Conclusion
The formation of methanol and other reaction products following the use of
DMDC for the treatment of alcoholic beverages and wine is similar to that
formed in non-alcoholic beverages. Therefore the previous opinion on the use of
DMDC for non-alcoholic beverages (1) is equally applicable to wines treated with
DMDC."

http://europa.eu.int/comm/food/fs/sc/scf/out96_en.pdf

Rue de la Loi 200, B-1049 Bruxelles/Wetstraat 200, B-1049 Brussel - Belgium -.
Telephone: direct line (+32-2) 295.81.10 / 296.48.70, exchange 299.11.11.
Fax: (+32-2) 299.48.91
Telex: COMEU B 21877. Telegraphic address: COMEUR Brussels.

http://www.europa.eu.int/comm/dg24/health/sc/scf/index_en.html
EUROPEAN COMMISSION
HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL
Directorate C - Scientific Opinions
C2 - Management of scientific committee; scientific co-operation and networks
Scientific Committee on Food
SCF/CS/ADD/CONS/43 Final

12 July 2001
Opinion of the Scientific Committee on Food
on the use of dimethyl dicarbonate (DMDC) in wines
(opinion expressed on 11 July 2001)

SCF/CS/ADD/CONS/43 Final
Opinion of the Scientific Committee on Food
on the use of dimethyl dicarbonate (DMDC) in wines
(opinion expressed on 11 July 2001)

Terms of Reference
The Committee is asked to indicate if its conclusions on the safety of
dimethyl dicarbonate (DMDC) used in non-alcoholic beverages is also
applicable to its use in wine.

Background
DMDC was evaluated by the SCF in 1990 and considered acceptable for the cold
sterilization of soft drinks and fruit juices at levels of addition up to 250
mg/L (1).
At that time no application for its use in alcoholic beverages
and wines had been made. The EC Directive 95/2 of 1995 (2) authorised the
use of DMDC as preservative only for non-alcoholic aromatised beverages,
alcohol-free wine and liquid tea concentrates at a maximum level of addition
of 250 mg/L with no detectable residues. In 1996 the Committee also
considered some further aspects of DMDC in response to a request from the
French authorities (3). This opinion did not alter the Committee's earlier
opinion.

The FDA in 1988 allowed the use of DMDC to prevent the growth of yeast in
wine and for the inhibition of yeasts in alcohol-free wine and low alcohol
wines by the addition of up to 200 mg/L provided the initial yeast counts
were reduced to less than 500 viable cells per ml after an initial
filtration or pasteurisation. DMDC is used to stabilise slightly sweet white
wines and unfiltered red wines (4).

DMDC was also evaluated in 1990 by JECFA (5) which considered it
inappropriate to establish an ADI taking into account that the compound
hydrolyses in aqueous media and that residual levels are below analytical
detection limits. It was
considered acceptable as a coldsterilising agent for beverages up to a level
of addition of 250 mg/L.

Evaluation
DMDC decomposes primarily to CO2 and methanol and forms minute amounts of
reaction products such as carboxymethoxylation products of naturally
occurring amines, amino acids, sugars and fruit acids (lactic acid, citric
acid, tartaric acid, ascorbic acid) (total carboxymethoxy derivatives 1.7-5
mg/L). In the presence of ammonia or ammonium ions small amounts of
methylcarbamate (< 25 µg/L) are formed. In the case of alcoholic and
nonalcoholic beverages other reaction products with methanol such as
monomethylcarbonate and dimethylcarbonate were identified and in the case of
alcoholic beverages the reaction product with ethanol, i.e.
methylethylcarbonate, was also detected (8.2-10.3 mg/L).

The toxicology data on DMDC and its reaction products, including those
formed by reaction with ethanol, were previously assessed by the SCF (1). It
was concluded that they were not of concern.

The amount of methylcarbamate formed in wine is unaffected by the presence
of ethyl alcohol and depends only on the presence of ammonia or ammonium
ions as occurs with nonalcoholic beverages. Further analyses of treated
wines stored for 12 months have shown no increase in ethylcarbamate beyond
background levels.

The use of 200 mg DMDC/L would add 98 mg/L of methanol to wine which already
contains an average of about 140 mg/L from natural sources. A healthy person
metabolises 1500 mg methanol/hr without any physiological problems and this
should be compared to the amount of up to 240 mg/L methanol in wine, treated
with DMDC up to 200 mg/L. Metabolism of the amounts of methanol resulting
from consumption of wine containing such levels is therefore well within the
capacity of the human body. Thus consumption of even large quantities of
wine would not pose any hazards from methanol.

Conclusion
The formation of methanol and other reaction products following the use of DMDC
for the treatment of alcoholic beverages and wine is similar to that formed in
non-alcoholic beverages. Therefore the previous opinion on the use of DMDC for
non-alcoholic beverages (1) is equally applicable to wines treated with DMDC.

References:
1. Scientific Committee on Food (SCF) (1990) Report on a second series of
food additives of various technological functions (opinion expressed on 19th
October 1990).  Twenty-sixth series of Reports of the SCF. Office of Official
Publications of the
European Communities, Luxembourg. pp 9-10.

2. European Parliament and Council Directive 95/2/EC on food additives other
than colours and sweeteners. O.J. No. L 61 18.3.1995, p. 1

3. Scientific Committee on Food (SCF) (1996). Opinion on dimethyldicarbonate
(DMDC; Velcorin) (Response to comments of the French authorities), Opinion
expressed on 7 June 1996. Thirty-ninth series of Reports of the SCF. Office of
Official Publications of the European Communities., Luxembourg, 2000 pp 23-26.

4. US Food and Drug Administration (FDA) (1988) Federal Register
53:41325-41329. 21 October, 1988.

5. Joint FAO/WHO Expert Committee on Food Additives and Contaminants (JECFA)
(1991) Thirty-seventh report of JECFA, WHO Technical Report Series N°. 806,
WHO, Geneva
*******************************************************************

>Date: Mon, 19 Jan 2004 16:09:04 -0500
>From: Donnie <mickiemc@...>
>
>To: Betty Martini <Bettym19@...>
>Subject: [Filtered] Dimethyl dicarbonate
>
>Betty,
>
>This additive is going to be used in juices, etc. It breaks down to
>methanol. Doesn't sound very safe, to me.
>
>Dimethyl dicarbonate
>an antimicrobial that is added to juices and acts on microbes contained
>in the juice, it is also listed as an approved food-contact substance on
>the FDA¹ inventory for use in non-carbonated juice beverages
>
>Some info on it, but there is a lot more on Google.
>
>http://www.analox.com/tbmeth019944b.htm
>
>Donnie
********************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

http://google.com  gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com  finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com  28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com  gives 291,700, the top 7 of 10  being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp  gives 85,700 websites,  top 8 of 10  anti.
http://www.ncbi.nlm.nih.gov/PubMed   lists 742 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 1052 posts in a public searchable archive  125 members

http://groups.yahoo.com/group/aspartame/messages 759 with 16,425 posts

http://groups.yahoo.com/group/aspartameNM/message/1024
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 9.5.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall


http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame (12.4.2): 59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall  EU Scientific Committee on Food, a whitewash

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall

Dr. Woodrow C. Monte  Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984;  36 (1):  42-54.
(62 references)   Professsor of Food Science [retired 1992]
Arizona State University,  Tempe, Arizona 85287  woodymonte@...
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame.  The EPA limit for water is 7.8 mg daily
for methanol (wood alcohol), a deadly cumulative poison. Many users
drink 1-2 L daily. The reported symptoms are entirely consistent
with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but,
like all juices, has 16 times more ethanol, which strongly protects
against methanol.)

"Fruit and vegetables contain pectin with variable methyl ester
content. However, the human has no digestive enzymes for pectin (6, 25)
particularly the pectin esterase required
for its hydrolysis to methanol (26).

Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3).  In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6)  (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120 deg C produced
only traces of methanol (3).  Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).  Entrapment of these
volatiles probably accounts for the elevation in methanol levels of certain
fruits and vegetable products during canning (31, 33)."

Recent research [see links at end of post] supports his focus on the
methanol to formaldehyde toxic process:

"The United States Environmental Protection Agency in their Multimedia
Environmental Goals for Environmental Assessment recommends a minimum
acute toxicity concentration of methanol in drinking water at 3.9 parts
per million, with a recommended limit of consumption below 7.8 mg/day
(8). This report clearly indicates that methanol:

"...is considered a cumulative poison due to the low rate of excretion
once it is absorbed.  In the body, methanol is oxidized to formaldehyde
and formic acid; both of these metabolites are toxic." (8)...

Recently the toxic role of formaldehyde (in methanol toxicity) has been
questioned (34).  No skeptic can overlook the fact that, metabolically,
formaldehyde must be formed as an intermediate to formic acid
production (54).

Formaldehyde has a high reactivity which may be why it has not been
found in humans or other primates during methanol posisioning (59)....

If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave.

Formaldehyde is a known carcinogen (57) producing squanous-cell
carcinomas by inhalation exposure in experimental animals (22).  The
available epidemiological studies do not provide adequate data for
assessing the carcinogenicity of formaldehyde in man (22, 24, 57).

However, reaction of formaldehyde with deoxyribonucleic acid (DNA)
has resulted in irreversible denaturation that could interfere with DNA
replication and result in mutation (37)..."
********************************************************************


[Non-text portions of this message have been removed]

http://groups.yahoo.com/group/aspartameNM/message/1051
European Union aspartame reevaluation status? Schwarcz communications:
Martini: Linsley: Murray 1.20.3 rmforall

Jan 20 2004

Betty Martini,  can you let me know what you know about the reevaluation of
aspartame and of stevia in the European Union, voted for by the European
Parliament April 19 2003?  Who on our side is monitoring it?  What
scientists are actually doing it, and when will it be done?

Hello Linda Linsley,  I really liked  your case story, which was obviously
sincere, and unusually clear and detailed.  I made the comments about your
writing style as a ploy to draw the skeptical scientist into feeling safe
about actually reading it, since I imagine that almost all of them
rigorously avoid reading any details about research against aspartame.
Certainly, none of them in five years have ever discussed research details
with me.

Their minds are set, and their identification with their fixed beliefs makes
them unable to take in and assess contarary evidence.   So, I write to them
to clarify my own understanding, and patiently lead them into a vague
awareness that I am good and competent, and represent a growing community of
citizens and scientists, and that they eventually may have to deal with
being on the "losing" team.

In Joe's case, he actually sent me his long aspartame defense, and then his
review of hangovers from formaldehyde from methanol, which led to me using
this material to show the strength of the anti-aspartame case, and to me
forwarding to him two excellent, lucid, polite rebuttals by Mark Gold.
It's highly unusual for an pro-aspartame professional  to write me more than
once, which is a clue that something is getting through to him.  For
instance, when he wrote, "There is a big difference between methanol
toxicity and "aspartame disease.", I see that his mind is starting to accept
the concept of "aspartame disease".

I hope you will take the time to make your case report as long and full of
details as possible, and include addresses for your many clinics and
doctors, and details from any available medical records and prescriptions.
This would be an invaluable contribution, and I will really put it out where
it will impact people.  Include everything-- summary of personal history,
family diseases, accidents, diet, spiritual growth, all the encounters with
doctors with names, addresses, and dates, quotes from your letters, posts,
and journals, all the drugs and treatments you've tried.  Every detail is
important.  There is nothing more potent and convincing than simple honesty.
Are any of your doctors listenning to you?

Use  http://google.com   and   http://www.ncbi.nlm.nih.gov/PubMed
to search   excitotoxins    or   gluten intolerance    to find out what you
want to know.

I've never found good evidence or consumer complaints against stevia.

In mutual support,  Rich
********************************************************************

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 11.22.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 9.11.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/989  On 4.10.2003
the European Union Parliament  voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall

  http://groups.yahoo.com/group/aspartameNM/message/1045
aspartame and formaldehyde toxicity discussion:
Schwarcz: Murray 12.13.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1049
let us examine an aspartame reactor: Schwarcz: Murray 1.18.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1050
existing proofs of aspartame (excitotoxin) toxicity:
Murray: Schwarcz: Gold 1.18.4 rmforall
********************************************************************

----- Original Message -----
From: "Linda Linsley" <lindalinsley@...>
To: "Rich Murray" <rmforall@...>
Sent: Monday, January 19, 2004 8:41 AM
Subject: Re: existing proofs of aspartame (excitotoxin) toxicity: Murray:
Schwarcz: Gold 1.18.4 rmforall

> thanks for these e-mails.  been watching from the
> side.  fascinating!  I was, at first, going to respond
> to this "Joe" guy about my own personal experience
> done in ignorance of the topic and controversy, but
> then I noticed in my scrolling that "I already had"!!!
> That surprised me, to say the least!
>
> [so what's so terrible about my style of writing??]
> Glad you could use it.
>
> Looked up the holisticmed site.  Why is stevia listed
> on the front page with a bunch of other harmful
> products?  Is it harmful too???
> thanks for your reply...I know you must be incredibly
> busy!
> linda
> --- Rich Murray <rmforall@...> wrote:
> >
> http://groups.yahoo.com/group/aspartameNM/message/1050
> > existing proofs of aspartame (excitotoxin) toxicity:
> > Murray: Schwarcz: Gold 1.18.4 rmforall

From: "Linda Linsley" <lindalinsley@...>
To: "Rich Murray" <rmforall@...>
Cc: <lindalinsley@...>
Subject: Re: existing proofs of aspartame (excitotoxin) toxicity: Murray:
Schwarcz: Gold 1.18.4 rmforall
Date: Monday, January 19, 2004 9:12 AM

Tell me more about excitotoxins, gluten, milk, wheat
and gelatin!  Had some more reactions and those were
on my next "hit list", as they were the only things
out of the ordinary.    thanks.  linda

From: "Dr. Betty Martini" <Bettym19@...>
To: "Rich Murray" <rmforall@...>
Subject: Fwd: [Filtered] [Aspartame Support] existing proofs of  aspartame
(excitotoxin) toxicity: Murray: Schwarcz: Gold 1.18.4  rmforall
Date: Monday, January 19, 2004 12:14 PM

Rich, don't you know who Joe Schwarcz is?  He's on the other side and has a
radio station in Canada.  I even sent him a packet with all the government
records.  He knows aspartame is poison.  He kept at me to get on his radio
program so he could turn it around so I wouldn't do it for a long
while.  Then he agreed if I would be in the radio station he would have Dr.
Blaylock on.  I did he didn't.  But I was ready for him, so when he made
accusations and started his spiel I said:  "I told you I would not play
games with you, etc."  He wrote me afterwards that for the first time he
got death threats.  I said: "So what did you expect trying to cover up the
issue."  You won't get anywhere with him.

Regards,  Betty
*******************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1050
existing proofs of aspartame (excitotoxin) toxicity:
Murray: Schwarcz: Gold 1.18.4 rmforall

From: "Mark D. Gold" <mgold@...>
To: "Rich Murray" <rmforall@...>
Subject: RE: let us examine an aspartame reactor: Schwarcz: Murray 1.18.4
rmforall
Date: Sunday, January 18, 2004 5:11 PM

> From: "joe.schwarcz" <joe.schwarcz@...>
>
> Here is the way science works:
> It is up to those making an allegation to prove it.  It is completely
> naïve to expect scientists to prove a negative, i.e. that aspartame does
> not cause  "aspartame disease."  I can't prove to you that we are not
> being visited by little green men from Mars even though I am convinced
> this is not the case.
> It is up to those who make the claim to come up with the physical
> evidence.
> There is a big difference between methanol toxicity and
> "aspartame disease."

Rich,

Thanks for your emails.

Somehow, I think significant physical evidence has already been seen:

1) extremely large number of persons suffering serious toxicity
reactions from short-term, medium-term and long-term aspartame use,

2) exposure to and accumulation of an extremely toxic poison from
aspartame ingestion,

3) the overwhelming preponderance of  ***independent***  research
finding problems with aspartame.

The reality is that it was up to the industry to demonstrate, in
pre-approval research, that their new chemical was likely safe. The
scientists and the FDA who reviewed the pre-approval research were so
appalled at the pre-approval studies they urged fraud prosecution of the
manufacturer. Since then, industry research has been designed and
conducted in a way that would avoid finding any problems. There is
nothing more damaging to people's attitudes about science then to
continue to condone or ignore years of misconduct (as is detailed at:
http://www.holisticmed.com/aspartame/abuse/ and
http://www.holisticmed.com/aspartame/aspfaq.html ).

I do agree with Dr. Schwarcz that aspartame poisoning is not exactly the
same thing as methanol or formaldehyde poisoning. The most important
reason, in my opinion, is that aspartame poisoning is caused largely by
the combination of the poison, formaldehyde and the free-form
excitotoxin derived from aspartame. The excitotoxin aspect of aspartame
is not often discussed now that people know that aspartame causes
gradual formaldehyde poisoning, but I think it is a very important
reason for the toxicity.

Best Wishes,  Mark Gold   Aspartame/NutraSweet Toxicity Info Center
12 East Side Dr., #2-18  Concord, NH 03301  603-225-2110
mgold@...
http://www.holisticmed.com/aspartame/
*******************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 1.18.4 rmforall

Rich Murray, MA   Room For All   rmforall@...
1943 Otowi Road, Santa Fe, NM 87505 505-986-9103
********************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1049
let us examine an aspartame reactor: Schwarcz: Murray 1.18.4 rmforall

Jan 18 2004    Well, Joe Schwarcz,

The only research that I've heard about that could have studied the actual
biochemical residuals of aspartame in humans only used three humans and did
not attempt using C-14 labelled methanol, although they did test both C-14
labelled phenylalanine and aspartic acid separately in their aspartame.
Would you like me to airmail you the zerox?

Their report in 1976 included only three human subjects, who were tested
with aspartame made with C-14 phenylalanine and then C-14 aspartate--
but never the methanol component!   Instead of mentioning the dreaded word
"formaldehyde" anywhere in the text and citations, they only showed, on
Figure 1,  Metabolic pathways followed by aspartame,  using arrows to show
reaction paths,

Asp-Phe-Me -->  intestinal esterases ---> Asp-Phe  +  MeOH  -->
one-carbon metabolic pool  -->  CO2 +  formyl metabolites

J Toxicol Environ Health. 1976 Nov; 2(2): 441-51.
Comparative metabolism of aspartame in experimental animals and humans.
Ranney RE, Oppermann JA, Muldoon E, McMahon FG.

Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid,
methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening
agent that organoleptically has about 180 times the sweetness of sugar.
The metabolism of aspartame has been studied in mice, rats, rabbits, dogs,
monkeys, and humans.
The compound was digested in all species in the same way as are natural
constituents of the diet.
Hydrolysis of the methyl group by intestinal esterases yielded methanol,
which was oxidized in the one-carbon metabolic pool to CO2.
The resultant dipeptide was split at the mucosal surface by dipeptidases and
the free amino acids were absorbed.
The aspartic acid moiety was transformed in large part to CO2 through its
entry into the tricarboxylic acid cycle.
Phenylalanine was primarily incorporated into body protein either unchanged
or as its major metabolite, tyrosine.   PMID: 827618

Their 1973 report clearly showed that 30% of C-14 labelled methanol in oral
aspartame was no longer being excreted from small monkeys after 8 hours.
What could this possibly be except toxic residuals in all body tissues of
the only possible biochemical products, formaldehyde and formic acid, both
cumulative?

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.

By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

These dire possibilities were confirmed in rats by the Trocho study in 1998.

The hundreds of case reports by aspartame reactors are entirely consistent
with chronic long-term, low-level toxicity from methanol or formaldehyde.

Doesn't this excite your curiosity?   Why not seize this obvious golden
opportunity to advance a sure-thing line of simple, easy research that can
quickly attain clear-cut results with immediate immense benefits to people--
benefits that are safe and inexpensive?

Why not question a few heavy users of aspartame, above 6 cans daily for
years?
If you find one with the typical symptoms, arrange to test his white blood
cells for DNA damage with the Comet assay, for $ 200.  Have him abstain,
monitor his symptoms, and retest the blood every month for six months.
Publish the results real-time on the Net, and invite discussion and
replications.

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall   [A detailed look at the data]

In mutual support,  Rich

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1045
aspartame and formaldehyde toxicity discussion:
Schwarcz: Murray 12.13.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD:
[formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4
*******************************************************************

From: "joe.schwarcz" <joe.schwarcz@...>
To: "Rich Murray" <rmforall@...>
Subject: RE: hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Murray 1.18.4
Date: Sunday, January 18, 2004 7:27 AM

Here is the way science works:
It is up to those making an allegation to prove it.  It is completely
naïve to expect scientists to prove a negative, i.e. that aspartame does
not cause "aspartame disease."  I can't prove to you that we are not
being visited by little green men from Mars even though I am convinced
this is not the case.  It is up to those who make the claim to come up
with the physical evidence.
There is a big difference between methanol toxicity and "aspartame disease."

Dr. Joe Schwarcz, Director   McGill Office for Science and Society
McGill University   801 Sherbrooke St. West  Montreal, QC.  Canada H3A 2K6
514-398-6238
********************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 1.18.4

----- Original Message -----
From: "Rich Murray" <rmforall@...>
To: <weekly@...>
Cc: <Robert_Swift_MD@...>; "joe.schwarcz" <joe.schwarcz@...>;
"Woodrow Monte" <woodymonte@...>; "Mark D. Gold"
<mgold@...>; <jonmargo@...>
Sent: Friday, January 16, 2004 10:21 PM
Subject: Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert
Swift, MD: [formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

[  http://groups.yahoo.com/group/aspartameNM/message/1045
aspartame and formaldehyde toxicity discussion:
Schwarcz: Murray 12.13.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1049
let us examine an aspartame reactor: Schwarcz: Murray 1.18.4 rmforall   ]

Jan 18 2004   Hey, Joe Schwarcz,   It's easy to toss off a  'shoot the
messenger' crack like "anti-aspartame fanatics are nuts".  Would you please
buttress your credibility as a scientist by citing specific faults in the
following mainstream scientific selections:

Rich Murray, MA    Room For All    rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-986-9103

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans)  is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems, and even seizures. In many cases
there is addiction.  Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Thrasher: Tephly: Monte: Murray 9.27.2 rmforall

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination,  as carbon dioxide in exhaled air
and as water in the urine.  They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body.  They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol.  This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg,
about 1 part per million [ppm] of the acute toxicity level of 2,000
mg/kg, 67,000 mmol/kg, used by McMartin (1979).  Two L daily use of
diet soda provides 123 mg methanol, 2  mg/kg for a 60 kg person, a dose
of 67 mmole/kg, a thousand times more than the dose in this study.
By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.]

Their followup report in 1976 included only three human subjects, who were
tested with aspartame made with C-14 phenylalanine and then C-14 aspartate--
but never the methanol component!   Instead of mentioning the dreaded word
"formaldehyde" anywhere in the text and citations, they only showed, on
Figure 1,  Metabolic pathways followed by aspartame,  using arrows to show
reaction paths,

Asp-Phe-Me -->  intestinal esterases ---> Asp-Phe  +  MeOH  -->
one-carbon metabolic pool  -->  CO2 +  formyl metabolites

J Toxicol Environ Health. 1976 Nov; 2(2): 441-51.
Comparative metabolism of aspartame in experimental animals and humans.
Ranney RE, Oppermann JA, Muldoon E, McMahon FG.

Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid,
methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening
agent that organoleptically has about 180 times the sweetness of sugar.
The metabolism of aspartame has been studied in mice, rats, rabbits, dogs,
monkeys, and humans.
The compound was digested in all species in the same way as are natural
constituents of the diet.
Hydrolysis of the methyl group by intestinal esterases yielded methanol,
which was oxidized in the one-carbon metabolic pool to CO2.
The resultant dipeptide was split at the mucosal surface by dipeptidases and
the free amino acids were absorbed.
The aspartic acid moiety was transformed in large part to CO2 through its
entry into the tricarboxylic acid cycle.
Phenylalanine was primarily incorporated into body protein either unchanged
or as its major metabolite, tyrosine.   PMID: 827618

[ At the end of this post are more lengthly details on industry bias in
aspartame, methanol, formaldehyde, formic acid research. ]

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Med Hypotheses. 1984 Jan; 13(1): 63-75.
Chronic methanol poisoning with the clinical and pathologic-anatomical
features of multiple sclerosis.
Henzi H.

The details of two cases of chronic methanol poisoning are presented. Both
patients initially developed clinical symptoms of multiple sclerosis: visual
disturbances, intention tremor, reduced abdominal reflexes, impaired
coordination and difficulties with walking. After the exposure to methanol
had ceased the multiple sclerosis symptoms persisted in patient 1 but
disappeared gradually in patient 2 (patient 2 had a history of excessive
alcohol consumption, which is a critical fact in this discussion).
Ultimately autopsies confirmed this picture: histological examination of
patient 1 revealed plaques in the spinal cord, in the stem and in the
proximity of the lower horn of one lateral ventricle, whereas no localized
demyelination could be found in patient 2. The results are discussed in
connection with the theory ("Methanol Hypothesis") that under certain
circumstances multiple sclerosis itself is induced by formaldehyde stemming
from the metabolism of methanol.   Publication Types:   Case Reports   PMID:
6708848

"This article outlines the case of a biology teacher whose chronic
formaldehyde exposure resulted in heightened sensitivity to formaldehyde,
three tonic-clonic seizures, and dramatic amnesia as well as other cognitive
dysfunction."
Robert B. Perna, Ernest J. Bordini, Maria Deinzer-Lifrak
A Case of Claimed Persistent Neuropsychological Sequelae of Chronic
Formaldehyde Exposure. Clinical, Psychometric, and Functional Findings
Archives of Clinical Neuropsychology 16 (1) (2001) pp. 33-44.
Arch Clin Neuropsychol. 2001 Jan; 16(1): 33-44. [27 citations]
A case of claimed persistent neuropsychological sequelae of chronic
formaldehyde exposure. Clinical, psychometric, and functional findings.
Perna RB, Bordini EJ, Deinzer-Lifrak M.
Comprehensive Neuropsychological Services of the Southern Tier, Vestal, NY

Many anecdotal cases and some clinical studies have demonstrated that
formaldehyde exposure can cause multiple health-related problems and
cerebral dysfunction.
The U.S. Consumer Product Safety Commission has documented multiple hazards
related to formaldehyde exposure.
Some of this research has suggested that low levels of exposure can be very
hazardous to one's health and can potentially result in heightened chemical
sensitivities, seizures, and cognitive decline.
Some research suggests that exposure results in long-term immunological
changes, cell neurofilament protein changes, and demyelination.
Symptomatically, exposure has been associated with respiratory problems,
excessive fatigue, headaches, mood changes, and impaired attention,
concentration, and memory functioning.
This article outlines the case of a biology teacher whose chronic
formaldehyde exposure resulted in heightened sensitivity to formaldehyde,
three tonic-clonic seizures, and dramatic amnesia as well as other cognitive
dysfunction.  PMID: 14590191

http://www.cpancf.com/
Clinical Psychology Asssociates of North Central Florida
Gainesville Office  2121 NW 40th Terr. Ste B.  Gainesville, FL 32605
Ph: (352) 336-2888  Fax: (352) 371-1730

Ocala Office  3002 SE 1st Ave., Bldg. 300  Ocala, FL 32  Ph: (352) 629-1100

http://www.cpancf.com/NRE00151.pdf
NeuroRehabilitation 17 (2002) 93-104 IOS Press
Advances and issues in the diagnostic differential of malingering versus
brain injury

Robert B Perna, Ph.D.  Neuropsychologist   Dr.Perna@...
Department: pain management
Facility: Southern Tier Pain Management Ctr.
Vestal, New York, 13850
Work Phone: 607-754-2313   Fax: 607-754-6926

http://www.usm.maine.edu/lac/ot/faculty%20&%20staff.htm
Robert B. Perna, Ph.D.; Part Time Instructor, OTH 610
Educational and Experiential Background
Robert is a part-time adjunct faculty who teaches Neuroscience in the
Occupational Therapy program. He is a clinical neuro-psychologist, the
director of a CARF accredited post-acute brain injury program, and is board
certified in psychopharmacology. He has completed many residencies at
University of Michigan Medical School and the Miami Heart Institute. He has
authored and co-authored more than fifty journal articles related to
neuro-psychology and rehabilitation.

http://www.forensicneuropsychology.com/_wsn/page2.html

http://www.psyfin.com/directory/detail.asp?ListingsID=7041

Ernest J.  Bordini Ph.D.  http://www.cpancf.com    cpancf@...
2121 NW 40th Terrace Ste B  Gainesville/Ocala, FL  32605
Phone: (352) 336-2888   Fax: (352) 371-1730
Licenses: Psychologist
Services: Clinical Psychology Associates of N. Central Florida, P.A.
provides services to children, adolescents, adultis, and seniors.
Psychological, Forensic and Neuropsychological Assessment. Employee
Assistance Programs.

Maria Deinzer-Lifrak, PhD  deinlif@...
Comprehensive Neuropsychological Services
490 Western Avenue    Albany, NY  12203   518-458-2314

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M  ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo.  Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male)  alemany@...

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ].  Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@...    919-684-3303, 660-5657
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall ]

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches.
Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA.   neurotulsa@...
Aspartame, a popular dietetic sweetener, may provoke headache in some
susceptible individuals. Herein, we describe three cases of young women
with migraine who reported their headaches could be provoked by chewing
gum sweetened with aspartame. [6-8 mg aspartame per stick chewing gum]

Here is a detailed personal case report.  The jumbled, run-together syntax
and multiple typos are also common in aspartame reactors who are just
starting to detox.  Note that this all unfolded within the last year, and
that symptoms are triggered by aspartame chewing gum, 6-8 mg aspartame per
stick.   Ms Linsley has exercised unusual initiative in searching out and
testing possible dietary triggers.  There are hundreds of similar reports in
the archives of  http://health.groups.yahoo.com/group/aspartame/messages ,
759 members and 16,419 posts in just over 5 years.

From: "Linda Linsley" <lindalinsley@...>
To: <aspartame@yahoogroups.com>
Subject: [Aspartame Support] Aspartame Poisoned
Date: Saturday, January 17, 2004 9:01 PM

Here's where I am at this point in time.

> I'm 50, a former athlete (my dad became an olympic
> coach), a self-learner and I always ask "why", "what
> happens if",etc. I learned a long time ago that just
> because someone "says so" isn't always enough. So
> when  things began to go wrong a year ago I recovered
> quickly from the shock and set out to find out what
> else it could be. Long story abbreviated:
> symptoms;(each time I re-tell this I remember more
> clearly what happened. my notes are tucked away
> somewhere). White flashes in eyes, re-curring
> dejavu's, dizziness, confusion, disorientation,
> nausea, vomiting, undescribable/unidentifiable tase
> and smell, thrown off feet/chair, head-bobbing, one
> time only--loss of consciousness while driving, foot
> bouncing off ground for no reason, incredible
> sleepiness that I HAD to stop for and pass out
> for(always had warning), inability to
> focus/concentrate, memory loss, decline in grammar
> and math skills, decline in reading and figuring out
> written/oral directions, disproportionate loss of
> muscle tone, stiffness, joint pain, asthma-like
> symptoms, hearing loss, vision changes, pains in
> chest and liver, poor coordination and balance, mood
> swings, depression, fatigue, when under physical
> stress/exertion my body would swell like arthritis(I
> could have sworn it was attacking itself!),
> reactions of doctors over the years; many tests, all normal.
> The first list of symptoms that involved the head were
> the ones I went for help with in 2002. Prior to that I
> was actually kicked out of my physicians office because
> I complained about all the tests and the money I spent
> on them. With a new doctor that I'd hardly been to,
> I was a bit hesitant. I didn't want to scare him, too,
> and get the reputation of being a hypochondriac, so
> I was real pleasant with him. He said I needed a
> psychiatrist. Second opinion, and third doctor, did
> mri, saw spots, referred me to neurologist, said to
> call him if I needed any help, tossed out phrase
> "m.s." POSSIBILITY, said needed more tests. When I
> had another episode while waiting for neurologist
> appointment that was 4 months away, he was merely
> polite. no help. Then I thought I'd mention a few
> more symptoms to him and he replied "You'd be surprised
> what we can imagine when we think there's something
> wrong with us". Finally saw neurologist, had second
> mri, spots the same. She said "Yes, you have the
> symptoms of m.s., but until you lose the use of an
> arm or leg for three days due to numbness and tingling,
> I won't even consider the possibility of it! Check the
> internet (but be careful--there's a lot of
> mis-information out there). Check with the M.S.
> Society!" I did. They said "Get a different doctor!" !
> I had noticed, on my own, that these "dejavu
> incidents" seemed connected to foods. I got a
> different doctor after a while. After the run I'd
> had with doctors, I was tired of the whole thing and was
> planning on only using the E.R. from then on. While
> in limbo between the old/new doctor, I practiced the
> diet a proffessor had told me about. His wife was
> diagnosed with m.s. and had recovered quite a bit on it.
> Things were going quite well as I was able to stick to it
> better (with new motivation). One day I had another
> "dejavu episode" and was worried that I didn't have
> a doctor I could rely on, as well as confused at what
> caused it. If my theory about food was right, then
> what happened? I was driving down the road at the
> time ( I'm a good compensator for the dizziness), and it
> was passed, so I popped a piece of gum in my mouth
> and THAT WAS IT! I had just bought another pack of
> Extra. I hadn't had any for a month now...same time when I
> was doing well! O.K.! If my theory was correct, then
> I could eat anything (within reason--I still wasn't
> sure yet) that I'd been avoiding and IF IT WAS the gum, I
> should have no other symptoms. (they would go in
> clusters for a period of 12-42 hours)..So I dropped
> the gum, pigged out on forbidden items and HAD NO
> TROUBLE AT ALL! The doctors refused to respond to
> and acknowledge that. When I got my new doctor, I said
> not much about it. I began to search the Internet. Found
> Dr. Betty Martini on the aspartame group, then
> Connie at the Kicksugar group, while also changing my
> experiments on myself which lead to discovering a
> variety of additives that were responsible for the
> symptoms. As I found out more additives I would
> check it out on the sites forconfirmation.
> foods I avoid now are aspartame, msg, hydrolyzed
> animal protien, aspartic acid, natural flavorings
> sucrose, dextrose, maltodextrin, corn syrup, high
> fructose corn syrup, disodium guanylate, monosodium
> glutamate, disodium phosphate( and any other "ate"),
> diglycerides and artificial flavorings.
> For now, that's the way things are.  Have I totally
> ruled out m.s. or something else? Not really because
> of the mri that showed spots on the brain.  Only
> time and consistency will prove anything. There seems to
> be a period of de-toxification when tolerance levels
> are better (saturation point?) during which I can
> indulge in damaging substances for a while with no
> reactions. However, saturation point is reached again and I
> notice tiny occurances of some of the earlier
> symptoms.  Sticking with the "pure diet" is
> difficult, especially when there are those around who don't
> follow it....and that's just about everyone I come
> in contact with!
> BUT THE RESPONSIBILITY LIES WITH ME
> to do what is best for me regardless of what is considered "normal".
********************************************************************

Sent: Jan 17 2003  3:35 PM    joe.schwarcz@...

Ohhhhh ...how a little learning is a dangerous thing...
The stuff about hangover is all correct, in fact I have written on it
myself (attached) but it has nothing to do with aspartame toxicity.  In
fact if you take the trouble to check with Dr. Swift you will learn that
he thinks the anti-aspartame fanatics are nuts.

Dr. Joe Schwarcz, Director   McGill Office for Science and Society
514-398-6238    joe.schwarcz@...
McGill University, 801 Sherbrooke St., West  Montreal, QC.  Canada H3A 2K6

"... But in all likelihood, the greatest contributor to the hangover is
methanol.  This alcohol is found in small concentrations in many beverages,
a byproduct of fermentation.  It is metabolized by the same enzymes as
ethanol, but the products this time are formaldehyde and formic acid which
produce the hangover symptoms.  Why does this happen only the morning after?
Because the enzymes prefer to work on ethanol instead of methanol.  Only
when all the ethanol has been metabolized, do they switch to methanol.... "

The Scoop On Booze
The police officers could hardly believe their eyes.  The eighteen year-old
driver they had just pulled over sat there speechless, a wad of white fabric
sticking out of his mouth.  He had ripped the crotch out of his underwear
and stuffed it into his mouth in an apparent attempt to fool the
breathalyzer.  Some scientific memory about the absorbency of cotton must
have stirred in his confused mind to prompt the bizarre act.  But the
breathalyzer was not fooled.  Neither was it fooled by the teenager who was
caught ferociously sucking on pennies after being stopped.  He must have
remembered a bit of the chemistry he had learned about alcohol.  The bit
about alcohol being oxidized to acetaldehyde by the action of copper.  He
figured he'd be in the clear since the breathalyzer tests for alcohol in the
breath, and not acetaldehyde.  Unfortunately the genius didn't remember the
reaction quite right.  Ethanol, the alcohol of beverages, can indeed be
converted to acetaldehyde by copper, but only when the copper is red hot!

Then there are those whose alibi is that they had just rinsed their mouth
with mouthwash.  But this doesn't wash either.  Sure, mouthwashes contain
alcohol, and a false breathalyzer reading is possible, but only if the
mouthwash was used immediately before giving a breath sample.  Alcohol from
a mouthwash dissipates within a couple of minutes and guidelines state that
a suspect has to be observed for several minutes before a breathalyzer test
is undertaken.

Is it surprising that people resort to such curious acts when they've
overindulged?  Not really.  After all, alcohol certainly affects the brain.
And the rest of the body as well.  The chemistry involved is absolutely
fascinating.  Of course, before alcohol can affect the brain, it has to get
there.  Most of the alcohol we consume is absorbed into the bloodstream from
the stomach and the small intestine.  But not all of the alcohol makes it
through.  Some is metabolized in the mucosa that lines the stomach and
intestine.  Here, enzymes convert ethanol first to acetaldehyde and then to
acetic acid, neither of which is inebriating.  In men, about 30% of a dose
of alcohol meets its metabolic end in this fashion, but there is a definite
gender bias here.  The female stomach and intestinal lining is only about
half as efficient at breaking down ethanol, so more makes it into the
circulation.  This explains why women may become tipsy more easily.

Once the alcohol is in the bloodstream, it passes through the liver.  The
liver is the body's main detoxicating organ and it detects alcohol as a
potential troublemaker.  First, an enzyme called alcohol dehydrogenase snips
a couple of hydrogen atoms out of the ethanol molecule, converting it to
acetaldehyde.  Then aldehyde dehydrogenase transforms this intermediate into
acetic acid which is either excreted or used by the body as a source of
energy as it is broken down into carbon dioxide and water.  A gram of
ethanol can provide about seven calories in this fashion.  If the intake of
alcohol is sufficiently high, the liver's detoxicating system becomes
overburdened and some of the alcohol slips through unmetabolized.  It can
then wreak havoc in the brain.

Ethanol does this by interfering with "neurotransmitters," the chemicals
brain cells use to communicate among themselves.  At low alcohol levels,
receptors for glutamate are activated leading to stimulation and a loss of
inhibition.  This is the "social lubricant" effect of alcohol.  But as the
concentration of alcohol rises, glutamate receptors actually become less
responsive and words begin to slur and "cocktail party amnesia" begins.
Other neurotransmitter systems are also affected.  Gamma aminobutanoic acid
(GABA) is known as an inhibitory neurotransmitter because it prevents nerve
cells from firing excessively.  Alcohol stimulates GABA activity which
eventually causes sedation and relaxation.  And that is only part of a very
complex picture.

Eventually the effects wear off as the alcohol is excreted or is metabolized
as it passes through the liver again.  But as this is happening, there is
often a matter of nausea, headaches and a flushed face to deal with.  The
culprit here is acetaldehyde, some of which escapes from the liver before
being converted to acetic acid.  As we well know, not everyone suffers these
symptoms to the same degree.  Many people of Asiatic origin are severely
affected by facial flushing because nature has dealt them a very slow acting
version of aldehyde dehydrogenase, the enzyme that normally degrades
acetaldehyde.  Indeed, the same concept lies behind a prescription drug
known as disulfiram (Antabuse) which is given to alcoholics.  The idea is
that the drug inactivates aldehyde dehydrogenase, forcing acetaldehyde into
the circulation.  This should make the drinker so sick that he gives up the
booze.  Unfortunately, he usually gives up the drug instead.

Some of the effects of acetaldehyde can linger till the morning after and
contribute to hangover.  Interestingly, the hangover business hasn't been as
extensively researched as one would think.  That's because solving the
problem would come with quite a bit of social baggage.  The concern is that
elimination of the hangover could cause people to drink more.  Still, we do
know that there is more to the hangover than just the remnants of
acetaldehyde.  The metabolism of alcohol in the liver produces some free
radical debris which is usually taken care of by glutathione, one of the
body's most important antioxidants.  When the system is overwhelmed, these
free radicals can contribute to the hangover.  That is why there has been
some success in treating hangovers with supplements of N-acetylcysteine
(NAC) which serves as a source of cysteine, the critical compound the body
needs to generate more glutathione.  Eggs also contain cysteine which may
explain their folkloric use to treat hangovers.

The hangover is actually multifactorial.  Dehydration plays an important
role as does hypoglycemia caused by the alcohol mediated loss of sugar in
the urine.  But in all likelihood, the greatest contributor to the hangover
is methanol.  This alcohol is found in small concentrations in many
beverages, a byproduct of fermentation.  It is metabolized by the same
enzymes as ethanol, but the products this time are formaldehyde and formic
acid which produce the hangover symptoms.  Why does this happen only the
morning after?  Because the enzymes prefer to work on ethanol instead of
methanol.  Only when all the ethanol has been metabolized, do they switch to
methanol.  This then explains the "hair of the dog" remedy for hangovers.  A
drink in the morning supplies ethanol for the enzymes to act on so they'll
leave methanol alone.  As the enzymes busily metabolize the ethanol,
methanol is excreted in the urine without being converted to formic acid.  A
Bloody Mary may be the best choice here, because vodka contains very little
methanol.  Confirmation about the critical role of methanol in hangovers
comes from a study showing that treatment with 4-methylpyrazole, a drug that
blocks the breakdown of methanol, can eliminate the symptoms.

I must admit to feeling a little queasy talking about hangover cures.
Alcohol can be an extremely destructive beverage.  It is probably more
damaging to society than all illicit drugs combined.  Cirrhosis of the
liver, strokes, breast cancer, oral cancers, domestic violence and sexual
assault have all been linked to alcohol abuse.  In North America there is an
alcohol related car accident every 30 seconds.  And if that isn't
frightening enough, excessive alcohol can shrink the genitals and have
feminizing effects on men.  Less testosterone is produced, so the sex drive
suffers.  But for those who want to look on the bright side, less
testosterone means less likelihood of baldness.

Henny Youngman, whom some would call a comedian, once remarked that when he
read about the evils of drinking he gave up reading.  I hope you won't do
the same.  There is nothing funny about being drunk.  Drunks destroy their
own lives and kill others.  What can we do?  Well, University of Georgia
researchers have found that blood alcohol can be reduced significantly by
inserting a tube into the rectum and piping in alcohol dehydrogenase and
oxygen.  Sounds good to me.
*******************************************************************

[more details on industry bias in aspartame, methanol, formaldehyde, formic
acid research]

In spring 1999, an eminent pro-aspartame scientist Christian Tschanz had
NutraSweet Co. give me their $ 130 review text of their research, "The
Clinical Evaluation of a Food Additive: Assessment of Aspartame" (1996), by
Christian Tschanz, Harriett H. Butchko, W. Wayne Stargel, and Frank N.
Kotsonis, all apartame stalwarts.

Chapter 5: "Metabolism and Pharmacokinetics of Radiolabeled Aspartame in
Normal Subjects", by Aziz Karim and Thomas Burns, has 10 pages and 10
citations. Page 63, Figure 4, Metabolic products derived from aspartame,
beta-aspartame, and DKP, does not list formaldehyde or fo