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

Aspartame and its effects on health, M.E.J. Lean, C. R. Hankey, British
Medical Journal: 11% methanol component of aspartame and same level of
methanol in dark wines and liquors, turns to formaldehyde, causing chronic
hangover symptoms: Murray

http://groups.yahoo.com/group/aspartameNM/message/1117
Aspartame and its effects on health, Michael E.J. Lean, Catherine R. Hankey,
Glasgow UK, British Medical Journal: 11% methanol component of aspartame,
and same level of methanol in dark wines and liquors, turns to formaldehyde
and formic acid, the main cause of chronic hangover symptoms: Murray
2004.10.04 rmforall

[ Comments by Rich Murray are in square brackets, where needed.
Texts are given in full, with spacing added for clarity and emphasis. I
start with a cogent summary critique, backed in full details by mainstream
sources cited throughout this long, often redundant post and its supportive
hyperlinks. ]

Lean ME has 123 studies and reviews in PubMed since 1981.

The value of this editorial, given in full text later in this post, is
adroitly revealed in its very first line:

"The European population of 375 million consumes about 2000 tonnes annually
of aspartame (NutraSweet, Canderel) an artificial sweetener, which contains
two amino acids -- aspartic acid and phenylalanine. (1 )"

Informed experts for three decades have both directly and fully, or
obliquely and misleadingly, if at all, summarized this primary fact about
aspartame:

Its 11% methanol component, which loosely binds the two familiar amino acids
together, is readily released above 86 degrees F, i.e., fully available in
the GI tract, and inevitably largely converted within hours in humans and
other species into formaldehyde and then formic acid, both potent,
cumulative toxins that affect every cell and tissue.

Fully 11% of aspartame is methanol -- 1,120 mg aspartame in 2 L diet
soda, almost six 12-oz cans, gives 123 mg methanol (wood alcohol) -- the
same amount that produces alcohol hangover as an impurity, about one part in
ten thousand, in dark wines and liquors, according to Ian Calder in British
Medical Journal, Jan 4, 1997.

If only 10% of the methanol is retained in the human body as cumulative
toxic products, that is a daily dose over sixty times the same 10% level of
accumulation for the 1 ppm USA EPA level of formaldehyde allowed to be
ingested in daily drinking water, 2 mg daily for 2 L water.

This year formaldehyde has been officially declared to be a human
carcinogen.

Its roles as a toxin, neurotoxin, genotoxin, hypersensitization agent,
allergen, and as the major cause of chronic alcohol hangover symptoms, are
explored widely -- PubMed lists 6219 studies for "formaldehyde symptoms".

Yet few are aware that aspartame is a ubiquitous potent source -- in fact a
few studies still blithely use aspartame as their control placebo.

It is evident that any adequate study of formaldehyde toxicity in humans
must directly determine the specific and full details of the actual chronic
biochemical disposition in hundreds of long-term heavy users, above 6 cans
daily diet soda for years, in the many and various vulnerable groups, using
realistic exposure protocols, while controlling for confounding variables,
including genetic variation, multiple sources of aspartame, methanol,
formaldehyde, formic acid, and MSG, common dietary deficiencies, use of dark
wines and liquors, tobacco and wood smoke, mobile homes, the possibility of
methanol from degradation of pectins from fruits and vegetables in the
colon, and folic acid, which is a protective agent that expedits the
elimination of formaldehyde.

Any lesser effort, such as the 1994 study by Mark L. Wolrich with 48 healthy
children fed for 3 weeks an average dose of aspartame about 35 mg/kg body
weight per day, 1,035 mg for a 30 kg child, which is just five diet sodas,
is bound, as no doubt planned by the vast vested interests that dominate
funding for decades for such public relations dramatizations of science, to
have the same results, for example, as studying the safety of tobacco by
having 48 kids smoke 10 cigarettes a day for 3 weeks, namely, precisely
nothing.

To their credit: "The use of various food components popularly believed to
influence behavior was kept to a minimum. These included artificial colors,
artificial flavors, additives, monosodium l-glutamate, chocolate, and
caffeine."

However, as is usually the case, nothing at all was said or studied about
methanol, formaldehyde, and formic acid toxicity from aspartame.

If the incidence of any symptom was actually 1%, a study would have to have
about 300 subjects exposed to test for that symptom to suggest safety at the
level of 1% incidence, which is a level of 1 million symtomatic in 100
million exposed.

It is exactly such data that is gathered as thousands of case reports via
the Net,
only to be disparaged by the many inadequate studies. Lane and Hankey:
"...but proving negatives is difficult, and it is even harder to persuade
vocal sectors of the public whose opinions are fuelled more by anecdote than
by evidence."

I notice in my own experience as a home hospice care giver in Santa Fe, New
Mexico since 1988, that about 5% of clients, and co-workers on all levels,
are using about 6 cans daily diet soda, while showing typical symptoms like
poor memory.

Mike Lean and Cathy Hankey: "Although no orchestrated public outcry about
aspartame has taken place, much sensationalist journalism has been published
mostly on websites (for example, www.holisticmed.com/aspartame/)."

I am very pleased that Lean and Hankey dare cite this site, which gives the
most sober, balanced, thorough, detailed critical assessments, from 1985
on, of mainstream scientific research available in the world, thanks to the
layman volunteer expert, Mark D. Gold. Since Jan 1999 I have learned from
his work and example and walked in his path:

http://www.HolisticMed.com/aspartame mgold@...
Aspartame Toxicity Information Center Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301 603-225-2110
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

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

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 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 ( 2002.12.04 ): 59 pages, 230 references

It is everyone's task not to duped and used by the skillful suations of
adroit manipulators in the employ of vast corporate vested interests, but
the evidence is that their influence has been and is profound. If we
succumb to such purveyors of confusion, we contribute to their own
increasing confusion and suffering.

To systematically ignor and deny the central issue of methanol toxicity is
as potent a public relations strategy as it is pretend science and extremely
inadequate medicine.

It is the extreme simplicity of this central issue that allows careful,
cheeky laymen, unqualified, earnest, and informed, to play the vital role of
waterboys, carrying simple facts from one specialized network of busy,
preoccupied experts to the next.

Our entire credibility and successful service can only derive from
consistent, thorough, fair, balanced, and civil mobilization of credible
mainstream evidence.

We serve thusly for the fun of it. Eminent reader, I have brought my full
pails to you. My task is done. Yours begins, according to your choice.
Take what you want, use it as you will, as you must. Science is
evidence-based cooperation for the greater good, the actual truth, which
expresses itself in part as our evolving lives within the convincing
framework of daily human experience. I am grateful for this marvelous
opportunity to play a small part in your network of mutual service.

With respect for Lean's two reviews in 1993 and 1994 about schizophrenia,
I hasten to ally any misperceptions that I am a polarized fanatic about
aspartame toxicity by listing two long appreciative reviews that explore
evidence that low doses of aspartame, methanol, and formaldehyde may be of
benefit for some conditions, especially schizophrenia:

http://groups.yahoo.com/group/aspartameNM/message/1055
hormesis: possible benefits of low-level aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti: Murray 2004.03.11 rmforall

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 2004.03.13 rmforall

With respect for Lean's two reviews in 1998 and 1999 on: "...DNA damage
from hydrogen peroxide (100 micromol/L) in human lymphocytes were examined
by using the single-cell gel electrophoresis assay (comet assay), I list
similar studies by Yu F. Sasaki's expert team using the same approach to
prove DNA genotoxicity in mice tissues from single large oral doses of many
food
additives and sweeteners, including nearly significant results for
aspartame.

Finally, an intripid and much published team in Japan has found DNA damage
in 8 tissues from single non-lethal doses of aspartame (near-significant
high levels of DNA damage in 5 tissues) and many other additives in groups
of just 4 mice:

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 (2000 mg/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 100 mg/kg).

Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced
DNA damage in the colon at close to the acceptable daily intakes (ADIs).

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

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 2002.12.31 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 2003.01.01 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. Methanol is the only component of aspartame that can lead
to DNA damage. ]

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 2003.01.27 rmforall [A detailed look at the data] ]

J Toxicol Sci. 2002 Dec; 27 Suppl 1: 1-8.
[Genotoxicity studies of stevia extract and steviol by the comet assay]
[Article in Japanese]
Sekihashi K, Saitoh H, Sasaki Y. yfsasaki-c@...
Safety Research Institute for Chemical Compounds Co., Ltd., 363-24 Shin-ei,
Kiyota-ku, Sapporo 004-0839, Japan.

The genotoxicity of steviol, a metabolite of stevia extract, was evaluated
for its genotoxic potential using the comet assay.
In an in vitro study, steviol at 62.5, 125, 250, and 500 micrograms/ml did
not damage the nuclear DNA of TK6 and WTK1 cells in the presence and absence
of S9 mix.
In vivo studies of steviol were conducted by two independent organizations.
Mice were sacrificed 3 and 24 hr after one oral administration of steviol at
250, 500, 1000, and 2000 mg/kg.
DNA damage in multiple mouse organs was measured by the comet assay as
modified by us.
After oral treatment, stomach, colon, liver, kidney and testis DNA were not
damaged.
The in vivo genotoxicity of stevia extract was also evaluated for its
genotoxic potential using the comet assay.
Mice were sacrificed 3 and 24 hr after oral administration of stevia extract
at 250, 500, 1000, and 2000 mg/kg.
Stomach, colon and liver DNA were not damaged.
As all studies showed negative responses, stevia extract and steviol are
concluded to not have DNA-damaging activity in cultured cells and mouse
organs. PMID: 12533916

The moderated newsgroup, bionet.toxicology , has accepted 16 of my long
reviews since March 11:

Dr. Charles "Chuck" A. Miller III rellim@...
Associate Professor of Environmental Health Sciences
374 Johnston Building, SL29
Tulane Univ. School of Public Health and Tropical Medicine
1430 Tulane Avenue New Orleans, LA 70112 (504)585-6942
Bionet.toxicology news group http://www.bio.net/hypermail/toxicol/current

In mutual service, Rich Murray

Rich Murray, MA Room For All rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-501-2298

http://groups.yahoo.com/group/aspartameNM/messages
133 members, 1,117 posts in a public searchable archive
***************************************************************

"Fully 11% of aspartame is methanol -- 1,120 mg aspartame in 2 L diet
soda, almost six 12-oz cans, gives 123 mg methanol (wood alcohol) -- the
same amount that produces hangover from red wine."

Formaldehyde, an acknowledged human carcinogen, which is prevalent in
modern society, is a largely unacknowledged co-factor that must impact many
of the studies based on the Nurses Health Study.

One major source is the methanol impurity, about one part in ten thousand,
in dark wines and liquors, which is converted by the body into formaldehyde
and then formic acid, both potent, cumulative toxins that affect every
tissue, and are seen by experts as the main cause of the infamous "morning
after" hangover.

"Many pathophysiological disturbances occur during hangover, including
dehydration; metabolic acidosis; hypoglycaemia; disturbed prostaglandin
synthesis; abnormal secretion of vasopressin, cortisol, aldosterone,
renin, and testosterone; increased cardiac output; tachycardia; and
vasodilatation."

http://bmj.bmjjournals.com/search.dtl search to get free full text
British Medical Journal 1997 (4 January); 314(7073): 2.
Ian Calder, F.R.C.A. [ Tel/Fax: 0171 720 9279 Consultant Anaesthetist at
the National Hospital for Neurology and Neurosurgery,
London WCIN 3BG, UK ]

Editorials Hangovers: Not the ethanol - perhaps the methanol

"Chapman found that hangover symptoms were almost twice as common in
volunteers who drank 1.5 ml/kg [ body weight ] of bourbon whiskey - which
has methanol concentrations of 26 mg/l - as in those drinking the same dose
of vodka ( 3.9 mg of methanol per litre ). (5) [ For a 60 kg person, this
would be 90 mg bourbon, 0.09 l, giving 2.34 mg methanol, which led to twice
as many symptoms as the 0.35 mg methanol from vodka. The bourbon gave as
about as much methanol as an ounce of diet soda. ]

Pawan compared the hangover produced by different types of drink (but only
one brand of each) in his study of 20 volunteers. The severity of hangover
symptoms declined in the order of brandy, red wine, rum, whisky, white wine,
gin, vodka, and pure ethanol.(6) Vodka and pure ethanol caused only mild
headaches in two volunteers.

Jones has suggested that it is the metabolism of methanol to formaldehyde
and formic acid that causes symptoms of hangover, with quicker methanol
metabolisers suffering more.(7) The justification for this suggestion is
threefold:
the types of drink associated with more severe hangovers contain higher
levels of methanol;
the time course of methanol metabolism corresponds to the onset of symptoms;
and a small dose of ethanol, which blocks the formation of formaldehyde and
formic acid, provides an effective treatment for hangovers ("the hair of the
dog")."

Jones AW (1987) found next-morning hangover from red wine with
100 to 150 mg methanol
(9.5% w/v ethanol; 100 mg/l methanol = 0.01%, one part in ten thousand).

The expert review by Monte WC (1984) states: "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)...."
Table 1 lists red wine as having 128 mg/l methanol, about one part in ten
thousand.

Fully 11% of aspartame is methanol -- 1,120 mg aspartame in 2 L diet soda,
almost six 12-oz cans, gives 123 mg methanol (wood alcohol) -- the same
amount that produces hangover from red wine.

"Between a quarter and a half of drinkers claim not to experience hangover
symptoms despite having been intoxicated. (three citations)" This
indicates a remarkable range of individual vulnerability to formaldehyde and
formic acid exposure.

Other strong formaldehyde sources are tobacco and wood smoke, and the
particleboard and new furniture, carpet, and drapes especially concentrated
in mobile homes. Many personal care products contain formaldehyde; for
instance, leather shoes can cause foot dermatitis.

Similar levels of methanol, and its inevitable products in the human body,
formaldehyde and formic acid, can also ensue from fermentation of fruit
pectins in the colon.

http://www.channing.harvard.edu/nhs/questionnaires/pdfs/NHSI/2002.PDF
The Nurses Health Study for 2002 has one question for:
"Do you currently smoke cigarettes?"

two questions on low-calorie beverages with and without caffeine, at levels:
(glass, bottle, can)
never or <1 monthly, 1-3 monthly, 1 weekly, 2-4 weekly, 5-8 weekly, 1 daily,
2-3 daily, 4-5 daily, 6+ daily,

regular beer (1 glass, bottle, can), red wine (4 oz.), white wine (4 oz.),
liquor (vodka, gin, etc.), (1 drink or shot),

Artificially sweetened or plain yogurt ( 1 cup) Nutrasweet or Equal (1
packet [37 mg aspartame]) NOT Sweet 'N Low.

SlimFast often contains aspartame, as do many diet foods, yogurts, desserts,
chewing gum, candies, popsicles, medicines.

How many and what percentage use the 9 levels of low-calorie beverages?
Do the 6+ daily users have the largest positive correlations with a variety
of problems?
Any data for allergies and Multiple Chemical Sensitivity?
Chronic Fatigue Syndrome? Fibromyalgia?
Any data on mental health, besides Depression, clinician Dx?
I'm surprised there are no questions for migraine and headaches-- heavy use
of analgesics, including aspirin, may correlate with heavy aspartame use.
Any data for poor memory and dementia?
Any correlations will likely be increased for simultaneous heavy use of red
wine and tobacco smoking.
Any data for mobile homes and use of wood stoves?
Are there similar correlations for heavy use of fruits and fruit drinks?
Does increased folic acid weaken these correlations, since folic acid
facilitates the elimination of formaldehyde?
Is there a correlation with increased drop-out from the Nurses Health Study
from year to year?
Is there a correlation with death?

I will assemble a team to research these questions, unless one can be formed
within some research community.

What are the requirements for a protocol that would be acceptible to access
the database?
How much is this likely to cost for each year studied?
Is data analysis software provided?

I welcome comments and feedback.

In mutual service, Rich Murray, MA
**************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1114
review of sweeteners 2004, Weihrauch MR, Diehl V: formaldehyde from 11%
methanol component of aspartame, methanol in dark wines and liquors,
fermentation of fruits in colon, also smoke, new buildings, furniture,
drapes, carpets, personal products: available database from Harvard Nurses'
Health Study II of 91,249 women in 1991-1999: Murray 2004.09.18 rmforall

Rich Murray, MA Room For All rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-501-2298

http://groups.yahoo.com/group/aspartameNM/messages
133 members, 1,117 posts in a public searchable archive

C. Trocho (1998):
"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 1998.06.26: Murray 2002.12.22 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@...

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
Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats: Murray 2002.09.08 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 W.C. Monte. ]
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: 2002.12.09 rmforall

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 2002.07.16 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
Blumenthall & Vance: aspartame chewing gum headaches Nov 1997:
Murray 2002.07.28 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 ]

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:

http://www.HolisticMed.com/aspartame mgold@...
Aspartame Toxicity Information Center Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301 603-225-2110
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

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

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 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 ( 2002.12.04 ): 59 pages, 230 references

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.

http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review by American Dietetic Association Feb 2004,
Valerie B. Duffy & Madeleine J. Sigman-Grant: Murray 2004.05.14 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1070
critique of aspartame review, French Food Safety Agency AFSSA 2002.05.07
aspartamgb.pdf (18 pages, in English), Martin Hirsch:
Murray 2004.04.13

http://groups.yahoo.com/group/aspartameNM/message/622
Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity: Murray 2001.06.04 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, Ph.D. Department of Psychology
Brooks Rehabilitation Hospital
3599 University Boulevard, South Jacksonville, Florida 32216
(904) 858-7650 shirley.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.

http://groups.yahoo.com/group/aspartameNM/message/1077
eight depressed people react strongly to aspartame, Prof. Ralph G. Walton,
MD, 1993 double-blind study, full text: Murray 2004.04.26 rmforall

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
Simmons: Gold: Schiffman: Spiers:
aspartame toxicity: Murray 2001.06.04 rmforall two double-blind studies
***************************************************************

http://bmj.bmjjournals.com/cgi/content/full/329/7469/755 free full text

British Medical Journal
BMJ 2004; 329: 755-756 (2 October), doi:10.1136/bmj.329.7469.755
Lean, M. E. J. || Hankey, C. R.

Collections under which this article appears:

Other nutrition and metabolism

Editorial
Aspartame and its effects on health
The sweetener has been demonised unfairly in sections of the press and
several websites

Michael E J Lean, professor fax +44 141 211 4844
Division of Developmental Medicine, University of Glasgow, Royal Infirmary,
Queen Elizabeth Building, Glasgow G31 2ER, mcmn1h@...

[ In August 2004, he starts a 6-month fellowship from the LeverhulmeTrust
based at the University of Colorado. http://www.leverhulme.org.uk/
Gilliam Dupin gdupin@... ]

Catherine R Hankey, lecturer, University Department of Human Nutrition
Division of Developmental Medicine, University of Glasgow, Royal Infirmary,
Queen Elizabeth Building, Glasgow G31 2ER

[ Dr Catherine R Hankey: Lecturer org unit: Medicine - Developmental
Medicine C.Hankey@... ; c.r.hankey@... ]

http://content.nejm.org/cgi/content/full/330/5/301?ijkey=f2b4d0e306c3aab2cae9a73\
f353743e16b449fd2
free full text

The European population of 375 million consumes about 2000 tonnes annually
of aspartame (NutraSweet, Canderel) an artificial sweetener, which contains
two amino acids -- aspartic acid and phenylalanine. (1 )

It is 180 -- 200 times sweeter than sucrose, and almost half a million extra
tonnes of sugar would therefore be needed to generate the same sweetness.
Was the world screaming for all this sweetness, and what has it done to us?
Anyone searching the web on aspartame, launched in 1981 by Monsanto, the
manufacturer of NutraSweet, will find a vast catalogue of frightening
personal accounts attributing multiple health disasters to exposure to
aspartame. ( 1 ) Although no orchestrated public outcry about aspartame has
taken place, much sensationalist journalism has been published mostly on
websites (for example, www.holisticmed.com/aspartame/).

In contrast, aspartame marketing implies that it embodies a healthy way of
life and avoids obesity. Are these claims of hazards and benefits supported
by evidence?

Evidence does not support links between aspartame and cancer, hair loss,
depression, dementia, behavioural disturbances, or any of the other
conditions appearing in websites.

Agencies such as the Food Standards Agency, European Food Standards
Authority, and the Food and Drug Administration have a duty to monitor
relations between foodstuffs and health and to commission research when
reasonable doubt emerges. Aspartame's safety was convincing to the European
Scientific Committee on Food in 1988, ( 2 ) but proving negatives is
difficult, and it is even harder to persuade vocal sectors of the public
whose opinions are fuelled more by anecdote than by evidence. The Food
Standards Agency takes public concerns very seriously and thus pressed the
European Scientific Committee on Food to conduct a further review,
encompassing over 500 reports, in 2002. It concluded from biochemical,
clinical, and behavioural research that the acceptable daily intake of 40
mg/kg/day of aspartame remained entirely safe -- except for people with
phenylketonuria. ( 3 )

Does aspartame embody a healthy way of life and avoid obesity? In most
Western countries sugar provides around 10% of total calories ( about 200
kcal ( 837 kJ ), or 50 g daily ). If this were entirely replaced by a
non-nutritive, non-caloric sweetener such as aspartame then obesity could
indeed be vanquished-assuming these calories are not replaced due to
stimulation of appetite. We eat about 5 g aspartame annually, equivalent to
another kg of sucrose, whose 4000 kcal (16 740 kJ) could generate 0.5 kg
gain in weight. But evidence that aspartame prevents weight gain or obesity
is generally inconclusive, ( 4, 5) although in children, the consumption of
sugar sweetened soft drinks relates notably to increasing obesity, whereas
increasing "diet" drinks or fruit juice is inversely related to weight gain.
( 6 )

Dietary recommendations for the management of diabetes conclude that up to
10% of total energy can safely come from sugars but that artificial
sweeteners may help avoid weight gain. ( 7, 8 ) When sugar is consumed as
a
sweetener it is chemically identical with the sugar found in fruits, which
we are promoting keenly, and its metabolic effects are no different if
consumed in reasonable amounts even by people with diabetes. ( 8 ) Most
evidence points to fat as the main dietary culprit in obesity, and one
counterargument to the use of artificial sweetener instead of sugar includes
evidence that high sugar diets tend to be lower in fat. ( 9 ) Displacing
saturated fat would offer particular advantages by reducing risk of heart
disease. ( 10 ) Carried to extremes, large amounts of sucrose will
increase triglycerides, a key component of the metabolic syndrome, and turn
the tables back towards promoting heart disease. Its fructose component is
responsible for this hazard. ( 11 )

Artificial sweeteners are promoted to prevent dental caries, as sugars form
the main substrate for mouth bacteria. However, avoiding sugar does not
reduce dental caries dramatically in regions with high levels of caries. (
4 )

The dominant factors are fluoride deficiency and prolonged exposure to
sugar between meals. If children consume sweetened drinks between meals or
suck on sweet foods, resulting in prolonged periods of exposure to sugar,
then replacing the sugar with artificial sweeteners in such products has
some rationale. Children exposed to heavily sweetened foods develop a "sweet
palate," but those who take the plunge and take unsweetened drinks may
prefer them, which seems a better solution. ( 12 )

Why has aspartame been demonised by the world's press and countless
websites? Monsanto was in the public eye, accused of enthusiastic
dissemination of genetically modified plants and foods. People resent
interference with foods, and synthetic food components are regarded with
suspicion. However, aspartame comprises just two amino acids (aspartic acid
and phenylalanine). Could this present a risk? Phenylalanine is a natural
amino acid, and is toxic only in patients who have phenylketonuria.

Food labelling of sweetener is contentious. Six artificial sweeteners are
permitted in Europe, each with an acceptable daily intake. Consumers cannot
be expected to calculate cumulative daily intakes of each. Instead,
manufacturers are encouraged to use cocktails of sweeteners so it becomes
difficult for anyone to reach the acceptable daily intake of any sweetener
individually-adults need at least 10 cans of a drink fully sweetened with
aspartame alone to reach the acceptable daily intake of 40 mg/kg/day. When
using combinations of sweeteners, even high level consumers rarely exceed 10
mg/day. Intakes over 1g/day were needed to alter brain neurotransmitters
and provoke seizures in monkeys, and randomised controlled trials of high
doses
in humans have not shown any behavioural or other effects. ( 13, 14 )

The cynical conclusion is that there is probably too much sweetness and
never enough light, and the public probably needs protection against
misleading
websites.

Competing interests: None declared.

References

1. Aspartame Information Center. www.aspartame.org/ (accessed 28 Jul 2004).

2. European Commission. Health and Consumer Protection Directorate-General,
Scientific Committee on Food. Opinion of the scientific committee on food:
update on the safety of aspartame. SCF, 10 December 2002.
http://europa.eu.int/comm/food/fs/sc/scf/index_en.html (accessed 17 May
2004).

3. Navia JM. Carbohydrates and dental health.
Amer J Clin Nutr 1994; 59: 719-27.

4. Tordoff MG, Alleva AM.
Effect of drinking soda sweetened with aspartame
or high fructose corn syrup on food intake and body weight.
Amer J Clin Nutr 1990; 51: 963-9. [Abstract]

5. Drewnowski A. Review: intense sweeteners and energy density of foods:
implications for weight control. Eur J Clin Nutr 1999; 53: 757-63.
[CrossRef][ISI][Medline]

6. Ludwig DS, Peterson, Gortmaker SL. Relation between consumption of sugar
sweetened drinks and childhood obesity: a prospective, observational
analysis. Lancet 2001; 357: 505-8. [CrossRef][ISI][Medline]

7. Nutrition Sub-Committee, British Diabetic Association. Dietary
recommendations for people with diabetes. An update for the 1990's.
J Hum Nutr Diet 1991; 4: 393-412. [ISI]

8. Diabetes and Nutrition Study Group (DNSG) of the European Association for
the study of diabetes. Recommendations for the nutritional management of
patients with diabetes mellitus. Eur J Clin Nutr 2000; 54: 353-5.
[CrossRef][ISI][Medline]

9. Bolton Smith C, Woodward M. Dietary composition and fat to sugar ratios
in relation to obesity. Int J Obes 1994; 18: 820-8. [ISI]

10. Puska P, Vartiainen E, Tuomilehto J, Salomaa V, Nissinen A. Changes in
premature deaths in Finland: successful long-term prevention of
cardiovascular diseases. Bull WHO 1998; 76: 419-2. [ISI][Medline]

11. Hollenbeck CB. Dietary fructose effects on lipoprotein metabolism and
risk for coronary artery disease. Am J Clin Nutr 1993; 58: 800s-809s.
[Medline]

12. Birch LL. Development of food preferences.
Annu Rev Nutr 1999; 19: 41-62. [CrossRef][ISI][Medline]

13. Wolraich ML, Lindgren SD, Stumbo PJ, Stegink LD, Appelbaum MI, Kiritsy
MC. Effects of diets high in sucrose or aspartame on the behaviour and
cognitive performance of children. N Eng J Med 1994; 330: 301-7.
[Abstract/Free Full Text]
http://content.nejm.org/cgi/content/full/330/5/301?ijkey=f2b4d0e306c3aab2cae9a73\
f353743e16b449fd2
free full text

14. Butchko HH, Stargel WW. Aspartame: scientific evaluation in the
postmarketing period. Reg Toxic Pharma 2001; 34: 221-233 [CrossRef][ISI]

Rapid Responses:
Read all Rapid Responses
Fluoride Deficiency Non-Existent Carol S. Kopf, BS, MA bmj.com, 1 Oct 2004
[Full text]
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The New England Journal of Medicine
Volume 330: 301-307 February 3, 1994 Number 5
Effects of Diets High in Sucrose or Aspartame on The Behavior and Cognitive
Performance of Children.
Mark L. Wolraich,
Scott D. Lindgren, University of Maastricht, The Netherlands.
Phyllis J. Stumbo,
Lewis D. Stegink,
Mark I. Appelbaum,
and Mary C. Kiritsy
mark-wolraich@... ; teresa-marshall@... ;

Phyllis J. Stumbo, PhD Department of Preventive and Community Dentistry,
University of Iowa College of Dentistry (T.A.M., S.M.L., J.J.W., B.B.,
J.M.E.-G.)
Clinical Research Center, University of Iowa Roy H. and Lucille A. Carver
College of Medicine (P.J.S.), Iowa City, Iowa teresa-marshall@...

Appelbaum MI,
Department of Psychology, University of California, San Diego.

Kiritsy MC,
Dows Institute for Dental Research, College of Dentistry, University of
Iowa, Iowa City, USA.

ABSTRACT
Background Both dietary sucrose and the sweetener aspartame have been
reported to produce hyperactivity and other behavioral problems in children.
Methods We conducted a double-blind controlled trial with two groups of
children: 25 normal preschool children (3 to 5 years of age), and 23
school-age children (6 to 10 years) described by their parents as sensitive
to sugar.
The children and their families followed a different diet for each of three
consecutive three-week periods.
One diet was high in sucrose with no artificial sweeteners,
another was low in sucrose and contained aspartame as a sweetener, and
the third was low in sucrose and contained saccharin (placebo) as a
sweetener.
All the diets were essentially free of additives, artificial food coloring,
and preservatives.
The children's behavior and cognitive performance were evaluated weekly.
Results The preschool children ingested a mean (±SD) of 5600 ±2100 mg of
sucrose per kilogram of body weight per day while on the sucrose diet,
38 ±13 mg of aspartame per kilogram per day while on the aspartame diet,
and
12 ±4.5 mg of saccharin per kilogram per day while on the saccharin diet.
The school-age children considered to be sensitive to sugar ingested
4500 ±1200 mg of sucrose per kilogram,
32 ±8.9 mg of aspartame per kilogram, and
9.9 ±3.9 mg of saccharin per kilogram, respectively.
For the children described as sugar-sensitive, there were no significant
differences among the three diets in any of 39 behavioral and cognitive
variables.
For the preschool children, only 4 of the 31 measures differed significantly
among the three diets, and
there was no consistent pattern in the differences that were observed.
Conclusions Even when intake exceeds typical dietary levels, neither dietary
sucrose nor aspartame affects children's behavior or cognitive function.

Refined sugar (especially sucrose) and aspartame
(-aspartyl-l-phenylalanine-o-methyl ester) have each been considered a
possible cause of hyperactivity and other behavior problems in children ( 1,
2 ).

The presumed reaction to sucrose has been attributed to several possible
causes, including a rise in blood sugar shortly after ingestion, reactive
hypoglycemia several hours after ingestion, and an allergic response ( 3 ).

The presumed reaction to aspartame has been attributed to the possibility
that
its metabolism results in elevated plasma phenylalanine concentrations,
which in turn may alter the transport of essential amino acids to the
brain ( 1, 4, 5 ).

Despite subjective reports about the behavioral effects of sugar and
aspartame, most controlled studies have not found consistent adverse
effects ( 6, 7 ).

Previous studies with controlled designs have examined the
behavior of children immediately after a dietary challenge, but these
studies have been criticized for their brief duration and laboratory
settings ( 6 ). Some argue that preschool children may be especially
sensitive to sugar ( 8 ) and that its effects may vary depending on the
ratio of sugar to protein and carbohydrate in food recently consumed ( 6 ).
Such arguments have not resolved the issue of whether dietary sweeteners
have long-term behavioral effects.

Despite the lack of consistent objective data demonstrating the behavioral
or cognitive effects of sugar or aspartame, subjective reports of such
adverse effects continue to be widespread. Because sucrose and aspartame are
common components of children's diets, any possible relation between these
sweeteners and behavior is a major health concern. To test the hypothesis
that sucrose or aspartame affects behavior and cognitive performance in
children, we evaluated children placed on diets high in sucrose, aspartame,
or saccharin (placebo) in a double-blind study with a Latin square design
and a broad range of dependent measures.

Methods

Subjects

The subjects were recruited through advertisements in the popular media and
presentations at preschool programs. Sugar-sensitive children were
identified on the basis of reports by their parents.

Two cohorts of children were studied concurrently. One group consisted of 23
children of primary-school age (6 to 10 years) reported by their parents to
respond adversely to sugar, and the other group consisted of 25 normal
preschool-age children (3 to 5 years of age).

Design

The study protocol was approved by the University of Iowa Committee on
Research Involving Human Subjects. The subjects and their families were
placed on a different diet for each of three consecutive three-week periods.
One of the three diets was high in sucrose with no artificial sweeteners,
another was low in sucrose and contained aspartame, and
the third was low in sucrose and contained saccharin (the placebo).

All diets were essentially free of additives, artificial food coloring, and
preservatives.
Two of the diet sequences are shown in Table 1.

View this table: [in this window] [in a new window]

Table 1. Diet Sequences for Two Subjects in a Latin-Square Design for
Experimental Diets with a Random Distribution of Sham Diets.

The children, their families, and the research staff were kept unaware of
the sequence of the diets. This blinding was reinforced by visible changes
made weekly in the diets (sham diets), but the sweetener was changed only
every third week. Families were informed that the diets would change weekly
and were given a list of the dietary components that were either varied or
controlled. The parents were asked to identify the experimental variables
each week, if they could.

Provision of Diets

Immediately before the beginning of the study, a dietitian supervised the
removal of food from the children's home. During the nine-week study period,
all foods were provided for the subject and his or her immediate family.

Family members were allowed items not included in the diet when they were
out of the home and away from the subject, and coffee and alcohol were
allowed to remain in the home as long as they were not consumed by the
children.

The food was delivered in a van equipped to serve as a mobile testing
laboratory. All food was removed from the home at the end of each week, and
a new supply delivered. In addition, parents kept records of all food
consumed by the subjects and were encouraged to report any deviations from
the specified diet.

During each three-week diet period, foods were sweetened with sucrose,
aspartame, or saccharin, depending on which diet was assigned for that
period. Care was taken to keep the appearance of the sweetened products
identical, regardless of the sweetener used.

Sweetened foods included pure fruit juice, fruit, cereals, pudding, flavored
yogurt, cookies, fruit toppings, and bottled carbonated soft drinks. The
soft drinks were supplied by three national bottlers in unmarked but coded
bottles; unsweetened fruit juice and unsweetened cereal were provided by two
national distributors.

Small amounts of saccharin were used to sweeten items, such as condiments,
that were consumed in small amounts by the subjects during all nine weeks.

The use of various food components popularly believed to influence behavior
was kept to a minimum. These included artificial colors, artificial flavors,
additives, monosodium l-glutamate, chocolate, and caffeine.

Shortenings and oils used in the diets did not contain butylated
hydroxyanisole or butylated hydroxytoluene, and the use of frozen meats and
baked products treated with these antioxidants was kept to a minimum.

The three sham diets consisted of
abundant quantities of red and orange foods (diet A);
beef and pork, with only raw fruits and vegetables (diet B);
and chicken and fish, with only cooked fruits and vegetables (diet C) (Table
1).

Dietary Intake

Dietary intake was documented in diaries by the parents and reviewed weekly
with the dietitian. Parents were taught how to estimate the amounts of food
consumed, and each week they received seven diary sheets listing the daily
menus. The study design imposed no restrictions on the quantity of each food
consumed, and parents were asked not to restrict access to any food.

Compliance

To determine dietary compliance, 1 mg of ascorbic acid per milligram of
aspartame was added to foods sweetened with aspartame, and 1 mg of
riboflavin per 5 g of sucrose was added to foods sweetened with sucrose.
These concentrations provide at least 10 times the recommended dietary
allowances, (9) with the amount excreted roughly proportional to the amount
of sweetener ingested. Urine samples were obtained weekly and tested for
ascorbate, riboflavin, and creatinine ( 10, 11, 12 ).

Behavioral and Cognitive Measures

The children were initially evaluated by means of a structured psychiatric
interview with the parent (Diagnostic Interview Schedule for Children --
Parent Version), ( 13 ) the Wechsler Intelligence Scale for Children --
Revised ( 14 ) or the Wechsler Preschool and Primary Scale of Intelligence,
( 15 )
and the Wide Range Achievement Test -- Revised ( 16 ) (for school-age
children only).

At base line and during each of the nine weeks of the study, the subjects
were
evaluated with behavioral and cognitive measures hypothesized to be
sensitive to the effects of sweetener (Table 2). During base-line testing,
children were oriented to the tests, and appropriate levels of difficulty
were determined for the learning and academic tasks. This served to minimize
the effects of practice during the study period.

Motor activity was assessed with a solid-state device for measuring motion
( 28 ). Five-second time sampling was used to assess behavior and activity
levels during the performance of a writing or drawing task ( 29 ). Several
tasks (e.g., card sorting and academic tests) were too difficult to be
administered to the preschool children.

Children rated their mood and physical state on a visual-analogue scale (
20 )
adapted from a self-report measure used to assess the effects of stimulants
in previous studies ( 30 ). Measures were administered in the mobile
laboratory each week on the same day of the week and at the same time of
day.

In addition, structured ratings of specific types of behavior were completed
by
the children's parents, the children's teachers, and research assistants
(Table 2). For the preschool-age children, the teacher's rating was
completed by a preschool teacher or a care giver other than the mother.

View this table: [in this window] [in a new window]

Table 2. Cognitive and Behavioral Measures Administered Weekly.

Biochemical Tests

Base-line biochemical tests included a fasting sucrose-tolerance test and
fasting plasma amino acid analyses. Sucrose tolerance was calculated by
determining blood glucose concentrations in samples drawn at 0, 0.5, 1, 2,
3, and 4.5 hours after a sucrose drink (1.75 g per kilogram of body weight).

On the third, sixth, and ninth weeks of the study, postprandial blood
samples for plasma glucose and amino acid analyses were drawn 2 to 3 hours
after a meal and 30 to 60 minutes after the subject had drunk 250 ml (8 oz)
of an uncarbonated beverage (providing 170 mg of aspartame, 30 g of sucrose,
or 40 mg of saccharin).

Plasma glucose concentrations were assessed by the glucose-6-phosphate
dehydrogenase method. Plasma amino acid levels were determined with
automated amino acid analyzers (Beckman 121 MB; Beckman Instruments, Palo
Alto, Calif.), ( 31 ) and these calculations included the molar ratio of the
plasma phenylalanine concentration to the sum of the concentrations of the
other large neutral amino acids ( 32 ) sharing its transport to the brain.

Statistical Analysis

The analysis was designed to evaluate a large number of possible effects. At
the same time, it was important that significance levels not be set so
conservatively that we would incorrectly accept the null hypothesis despite
clinically important differences; for this reason, Bonferroni corrections
were not applied.

Similarly, multivariate analyses were not used because of concern about a
reduction in the degrees of freedom and difficulty in handling selective
missing data in such analyses. Separate repeated-measures analyses of
variance were carried out for each dependent variable, and individual
comparisons among the three treatments were made with Tukey's test, each at
the 0.05 level of significance.

Although this approach increased the chance of a type I error, it maximized
our ability to detect any differences attributable to the sweeteners. The
use of a counterbalanced Latin square design ( 33 ) eliminated the
possibility that practice or the sequence of the diets would account for
differences in the cognitive or
behavioral variables.

To increase the reliability of the cognitive and behavioral assessments, the
three scores obtained for each dietary period were averaged, and these mean
scores were compared by a repeated-measures analysis of variance.

To detect possible cumulative effects, the results from the final week of
each period were also compared.

In addition, analyses of variance were performed to determine whether the
sham diets had any influence on the cognitive and behavioral variables.

Dietary intake was calculated for each treatment period and for each sham
diet during that period. The intake of macronutrients, sweeteners, and
vitamin markers was tabulated, and differences were evaluated with an
analysis of variance.

To identify individual subjects who may have responded adversely to sugar or
aspartame, the weekly scores for each of nine core neurobehavioral measures
were ranked and examined to determine whether the poorest scores were
clustered during a particular dietary period. This approach was considered
preferable to setting a fixed cutoff point for differences (e.g., a 25
percent change) because of the wide variation in raw scores among the
variables studied and in score levels at different ages.

Results

Subjects

Fifty-eight subjects were recruited for the study. Pilot studies of the
first three subjects were used to refine the protocol; these children were
therefore eliminated from the final analysis. Three subjects were eliminated
because of poor compliance, as confirmed by the weekly urine tests for
ascorbate and riboflavin; three withdrew before completing the study; and
one (the youngest) was unable to complete the cognitive and behavioral
assessments.

The 48 remaining subjects (25 normal preschool children and 23 school-age
children thought to be sensitive to sugar) tended to have average academic
skills and above-average intellectual ability, with a mean IQ (±SD) of 125
±11 and 117 ±10, respectively (range, 95 to 144).

The mean number of years of maternal education was 15.5 and 14.7,
respectively (range, 12 to 20). The mean age was 4.7 years (range, 3 to 5)
in the preschool group and 8.1 years (range, 6 to 10) in the school-age
group; 48 percent of the younger children and 78 percent of the older
children were boys. No psychiatric disorders were identified in the
preschool group.

Five of the presumably sugar-sensitive children met the criteria for
attention-deficit disorder with hyperactivity, and two of the five also met
the criteria for oppositional defiant disorder; two other children met the
criteria for oppositional defiant disorder alone.

Dietary Consumption

The preschool children ingested a mean of
5600 ±2100 mg of sucrose per kilogram per day while on the sucrose diet,
38 ±13 mg of aspartame per kilogram per day while on the aspartame diet,
and
12 ±4.5 mg of saccharin per kilogram per day while on the saccharin
diet.

The respective values for the school-age children thought to be sensitive to
sugar were 4500 ±1200 mg of sucrose per kilogram,
32 ±8.9 mg of aspartame per kilogram, and
9.9 ±3.9 mg of saccharin per kilogram.

The mean daily intake of energy and macronutrients (protein, fat, total
carbohydrate, and sucrose), as well as saccharin, aspartame, riboflavin, and
ascorbate, is shown in Table 3. The intake values were calculated from the
dietary records, summarized separately for each experimental period and for
each sham diet.

The mean daily intake of total carbohydrate and sucrose was approximately 65
g and 82 g higher, respectively, during the sucrose diet than during the
other two
diets. The daily intake of sucrose, carbohydrate, and energy differed
significantly between the sucrose diet and the other two diets. Some small
but significant differences among the sham diets were also found for certain
variables. The parents of children completing the study reported only a
small number of dietary infractions, which were included in the dietary
analysis. Only one parent correctly identified the sequence of diets.

View this table: [in this window] [in a new window]

Table 3. Mean Daily Intake of Energy and Nutrients during the Three-Week
Diet Periods.

Behavioral and Cognitive Measures

The mean behavioral and cognitive variables are summarized in Table 4.

Two analyses were performed: one compared the mean values for the three-week
dietary periods, and the other compared the mean values for the third week
alone.

The differences were identical in the two analyses, except for differences
in pegboard performance, which were evident only in the analysis of the
three-week means. Because the analyses were so similar, only the three-week
means are presented.

View this table: [in this window] [in a new window]

Table 4. Cognitive and Behavioral Variables during the Three Diet Periods.

In the group of school-age children thought to be sensitive to sugar, none
of the 39 behavioral and cognitive variables differed among the three
dietary periods.

In the normal preschool group, there were no significant differences in the
31 variables, with two exceptions.

Parents' ratings on the cognition subscale of the Pediatric Behavior Scale
were significantly better during the sucrose diet than during the aspartame
and saccharin diets (P<0.008).

Pegboard performance was significantly slower during the sucrose diet (
Table
4 ), although it was still faster than average. No child in either group had
an adverse response to sucrose or aspartame.

Biochemical Tests

The results of the base-line fasting sucrose-tolerance test were reviewed by
a pediatric endocrinologist who was not one of the investigators. All the
profiles were within normal limits, except that four subjects had slightly
elevated glucose levels ( 173 to 187 mg per deciliter [ 9.61 to 10.4 mmol
per
liter ]) one half-hour after the sucrose drink, and four subjects had low
levels: three at two hours ( 55 to 59 mg per deciliter [ 3.06 to 3.28 mmol
per
liter ]) and one at one hour (50 mg per deciliter [ 2.78 mmol per liter ]).

Postprandial glucose concentrations in the two groups of subjects did not
differ significantly among the three diets.

Base-line plasma phenylalanine concentrations were similar in the two groups
( Table 5 ) and within the normal fasting range (mean of upper and lower
limits, 0.81 ±0.13 mg per deciliter [ 49.0 ±8.0 µmol per liter ]) ( 34 ).

Postprandial plasma phenylalanine concentrations and the ratio of
phenylalanine concentrations to the sum of the values for the other large
neutral amino acids were significantly higher than base-line values in both
groups during all three diets and were also significantly higher in both
groups during the aspartame diet than during the sucrose and saccharine
diet.

Postprandial plasma phenylalanine values were within the normal range
( mean of upper and lower limits, 1.29 ±0.19 mg per deciliter [ 78.1 ±11.8
µmol per liter]) in both groups during all three diets ( 34 ).

View this table: [in this window] [in a new window]

Table 5. Postprandial Plasma Phenylalanine and Glucose Concentrations and
the Ratio of Phenylalanine to Large Neutral Amino Acids, According to Diet.

To evaluate the suggestion that people who are allergic to sucrose may need
to be free of the nutrient before they respond to a challenge, we examined
the data for all the children who were on the sucrose diet during the third
dietary period. For each variable, the mean value for this period was
subtracted from the mean value for the placebo (saccharin) period and the
difference was compared with zero to determine whether there were any
significant differences. None were found.

Discussion

The results of this study do not support the hypothesis that a diet high in
either sucrose or aspartame adversely affects the behavior or cognitive
functioning of children.

There were few sweetener-related effects in either the preschool-age or the
school-age children, and none of the children in either group had a
consistently adverse response to either sucrose or aspartame.

The findings were negative even though the older children were selected
because their parents believed them to be sensitive to sugar and even though
the children in both groups ingested substantial amounts of the sweeteners.

Cognitive or behavioral differences were as likely to be found between sham
diets as they were between experimental diets, and the few differences
associated with the ingestion of sucrose were more consistent with a slight
calming effect than with hyperactivity.

The absence of effects in our study could have resulted from the use of
insensitive measures or an inadequate statistical power to detect small
differences, but neither explanation seems likely.

The measures we used have proved to be sensitive to hyperactivity, attention
deficits, and the effects of medications and foods in earlier research ( 21,
35 ).

In addition, the study design provided sufficient statistical power to
detect potential differences if they were present. On the basis of a
calculation of power that used three core measures from the three primary
sources of data (parents, teachers, and children), the study would have been
able to detect an effect with an average size of 0.4 SD with a probability
of approximately 0.55 or an effect with a size of 0.6 SD with a probability
of 0.9.

Given the large number of analyses, the number of differences found is no
higher than the number that would be anticipated by chance alone.

Despite the generally negative findings of this study, it is possible that
there are some children who respond adversely to sugar or aspartame. Our
subjects had average or above-average intelligence, and children with less
intellectual ability may respond differently.

However, the groups of children we studied should have maximized the
likelihood of finding dietary effects. One group was composed of children
whose parents considered them sensitive to sugar, and the other consisted of
preschoolers, a population reported to be sensitive to dietary effects (
8 ).

It could be argued that all three sweeteners had adverse effects. This
possibility seems unlikely because behavior ratings and test scores
generally improved during the dietary periods, as compared with the
base-line values.

Also, it is improbable that all three sweeteners could have had equally
adverse effects on each of the diverse variables studied.

It is particularly unlikely that our failure to observe any effects of
aspartame or sucrose ingestion on behavior reflects an insufficient
consumption of aspartame or sucrose.

Calculations by the Market Research Corporation of America ( 36, 37 )
indicate that the highest daily aspartame intake under normal conditions
ranges from 22 to 34 mg per kilogram, with a calculated 99th percentile of
34 mg per kilogram ( 37 ) -- a value close to that observed in our study (32
mg per kilogram in the school-age subjects and 38 mg per kilogram in the
preschool subjects).

Data on sucrose intake in children are scarce, and comparisons require
calculations. If the energy requirements of a 20-kg 4-to-6-year-old child
range from 1300 to 2300 kcal per day, with 17 percent of the energy provided
by sugar, ( 9 ) the sucrose intake ranges from 2800 to 4900 mg per
kilogram; similar calculations for a 28-kg 7-to-10-year-old child indicate
an intake of 2500 to 5300 mg of sucrose per kilogram. In our study, the
sucrose intake was 5600 ±2100 and 4500 ±1200 mg per kilogram in the
preschool and school-age children, respectively -- values clearly at the
upper end of the normal range.

Large increases in the plasma phenylalanine concentrations ( 24.78 ±3.80 mg
per deciliter [ 1500 ±230 µmol per liter ]) and in the ratio of
phenylalanine
to the sum of the other large neutral amino acids ( 4.17 ±1.42; normal
value,
0.11 ±0.01 ) are associated with adverse effects in children with
phenylketonuria ( 38 ). By comparison, these values were much lower in our
subjects (Table 5).

The slight increases noted in the children in our study while they were on
the aspartame diet would be unlikely to produce adverse effects,
particularly when these values are evaluated in the light of the data of
Waisbren and Levy and colleagues. Their data indicate that untreated mild
hyperphenylalaninemia ( 6.8 mg per deciliter [ 410 µmol per liter ]) in
women
was associated with a normal outcome in their offspring, including a normal
IQ ( 39, 40 ).

We conclude from this carefully controlled nine-week study that neither
sucrose nor aspartame produces discernible cognitive or behavioral effects
in normal preschool children or in school-age children believed to be
sensitive to sugar.

Supported by grants from the National Institute of Child Health and Human
Development (HD24751) and the Clinical Research Centers Branch (RR59),
National Institutes of Health, and
the Nutrition Foundation -- International Life Sciences Institute.

We are indebted to Dan Medenblik, Greg Peak, Lisa Marchman, Bridget
Zimmerman, Robert Woolson, and Helen DeEmden for assistance with this
research, and to General Mills, Libby's NutraSweet, Coca-Cola, PepsiCo, and
Royal Crown for supplying products for the study.

Source Information
From the Departments of Pediatrics (M.L.W.) and Psychology and Human
Development (M.I.A.), Vanderbilt University, Nashville, and the Department
of Pediatrics (S.D.L., L.D.S.) and the Clinical Research Center (P.J.S.,
M.C.K.), University of Iowa College of Medicine, Iowa City.
Address reprint requests to Dr. Wolraich at the Child Development Center,
2100 Pierce Ave., Nashville, TN 37232-3573.

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http://www.gla.ac.uk/departments/humannutrition/staff/lean.html

Professor MICHAEL E J LEAN : MA, MB BChir, MD, FRCP (Edin), FRCPS (Glas)
[ photo ]
Professor Lean, head of the Department of Human Nutrition, holds the Chair
of Human Nutrition at the University of Glasgow and is also a Consultant
Physician at Glasgow Royal Infirmary. He trained in medicine at the
University of Cambridge and St Bartholemew's.
After a brief spell as a heart surgeon in Edinburgh he concentrated on
general medicine, diabetes and endocrinology with an increasing interest in
the prevention of disease.

After clinical training mainly in Aberdeen, he returned to Cambridge to join
the scientific staff of the MRC-University of Cambridge Dunn Nutrition
Unit.Here he developed a research career in nutrition, specialising in
obesity and energy balance and completed higher professional training in
diabetes.
In 1992 he was appointed to his present position, teaching and directing
research into human nutrition and its impact on many different aspects of
health and medical practice. He maintains clinical input in General Acute
Medicine and with the Nutrition Support Team.
He has increasingly become involved in public health and health promotion to
prevent disease and promote good health through healthy eating. From 1995 to
2003 he was a Non-executive Director of the Health Education Board for
Scotland.
From 2002, he has been Chairman of the Advisory Committee for Research of
the Food Standards Agency based in London.
In August 2004, he starts a 6-month fellowship from the LeverhulmeTrust
based at the University of Colorado.

http://www.gla.ac.uk/departments/humannutrition/staff/leancv.html
Curriculum Vitae

http://www.gla.ac.uk/departments/humannutrition/staff/leanpub.html
Publications

Int Clin Psychopharmacol. 2004 Jan; 19(1): 31-5.
Schizophrenia and osteoporosis.
Lean M, De Smedt G.
Department of Human Nutrition, University of Glasgow, Glasgow Royal
Infirmary, Glasgow, UK. mej.lean@...

Although it has been suggested that antipsychotic-induced
hyperprolactinaemia in schizophrenic patients may lead to an increased risk
of osteoporosis, this has not been proven.
Osteoporosis is a multifactorial disease, and untreated patients with
schizophrenia are at risk due to both the consequences of the disease and
related lifestyle factors. Evidence from available studies does not show
that antipsychotic-induced hyperprolactinaemia is an independent risk factor
for osteoporosis in schizophrenic patients.
Osteoporosis would be expected in women who develop amenorrhoea as a result
of hyperprolactinaemia secondary to antipsychotics, but there is no
plausible mechanism in men.
The uncertainty over this issue underlines the need for full medical and
metabolic assessment and monitoring of psychiatric patients.
Publication Types: Review Review, Tutorial PMID: 15101568

http://care.diabetesjournals.org/cgi/content/full/26/5/1597 free full text

Diabetes Care. 2003 May; 26(5): 1597-605.
Comment in:
Diabetes Care. 2003 Nov; 26(11): 3200-1.
Patients on atypical antipsychotic drugs: another high-risk group for type 2
diabetes.
Lean ME, Pajonk FG. mej.lean@...
Department of Human Nutrition, University of Glasgow, UK.
Frank-Gerald Pajonk, MD
Department of Psychiatry and Psychotherapy, the Saarland University
Hospital, Homburg, Germany
[ Klinik fur Psychiatrie und Psychotherapie, Universitatsklinikum des
Saarlandes. frank.pajonk@... ]

Received for publication 9 September 2002 and accepted in revised form 12
February 2003.
M.E.J.L. has received honoraria for speaking engagements from Roche,
Janssen-Cilag, Abbott, and Merck and research funds from Sanofi-Synthelabo,
Roche, Janssen-Cilag, GlaxoSmithKline, and Alizyme Therapeutics. F.-G.P. is
employed by Janssen Cilag.

Patients with schizophrenia are more likely than the general population to
develop diabetes, which contributes to a high risk of cardiovascular
complications; individuals with schizophrenia are two to three times more
likely to die from cardiovascular disease than the general population.
The risk of diabetes, and hence cardiovascular disease, is particularly
increased by some of the new atypical antipsychotic drugs.
Individuals taking an atypical antipsychotic drug, particularly younger
patients under 40 years of age (odds ratio 1.63, 95% CI 1.23-2.16),
represent an underrecognized group at high risk of type 2 diabetes.
The mechanisms responsible for antipsychotic-induced diabetes remain
unclear. Hypotheses include these drugs' potential to cause weight gain,
possibly through antagonism at the H(1), 5-HT(2A), or 5-HT(2C) receptors.
Other mechanisms independent of weight gain lead to elevation of serum
leptin and insulin resistance.
Patients with psychoses have difficulties with diet and lifestyle
interventions for diabetes and weight management.
If hyperglycemia develops, withdrawal from antipsychotic medication will
often be inappropriate, and a change to an atypical antipsychotic drug with
lower diabetogenic potential should be considered, especially in younger
patients.
Management of psychoses should routinely include body weight and blood
glucose monitoring and steps to promote exercise and minimize weight gain.
Careful collaboration between the psychiatric and diabetology teams is
essential to minimize the risk of diabetes in patients taking atypical
antipsychotic medication and for effective management when it develops.
This collaboration will also help minimize the already high risk of
cardiovascular disease in individuals with schizophrenia.
Publication Types: Review Review, Academic PMID: 12716824

http://konstanza.ingentaselect.com/vl=15182686/cl=12/nw=1/rpsv/cgi-bin/cgi?body=\
linker&ini=nlm&reqidx=issn=0029-6651vl=59is=3yr=2000mn=Augpg=331
free full text

Conjoint Congress of the Nutrition Society and Sociedad Española de
Nutrición was held at the University of Navarra,
Pamplona, Spain, on 8-11 September 1999
1st Plenary Session on 'Obesity'

Proc Nutr Soc. 2000 Aug; 59(3): 331-6.
Pathophysiology of obesity.
Lean ME.
Department of Human Nutrition, University of Glasgow, Glasgow Royal
Infirmary, UK. mej.lean@...

The rapidly rising prevalence of obesity, worldwide, has prompted
re-evaluations of the definitions and diagnostic criteria, and of the extent
of the burden it contributes to health care services.
Although categorized arbitrarily for epidemiological purposes according to
BMI > 25 kg/m2 ('overweight') and BMI > 30 kg/m2 ('obese'), the disease
itself (ICD code E.66) is the process of excess fat accumulation.
It leads to multiple organ-specific pathological consequences, particularly
if there is a tendency to intra-abdominal fat accumulation.
The simplest field method to identify obesity and risk of medical problems
is the waist circumference, and this method has found a special role in
health promotion. Risks begin with waist > 80 cm (women) or > 94 cm (men).

As a broad generalization, obesity produces few symptoms below the age of 40
years, but then several symptoms often develop; tiredness, breathlessness,
back pain, arthritis, sweatiness, poor sleeping, depression and menstrual
disorders all being common. [ These are all common symptoms reported by
aspartame reactors. ]

The symptoms are often attributed to diseases in other body systems.
Metabolic diseases like diabetes, hyperlipidaemia and, hypertension develop
later, but the mean BMI at diagnosis of diabetes is 28 kg/m2.
Ultimately, obesity increases the likelihood of myocardial infarction,
stroke and several major cancers, but its biggest impact on health,
especially in the elderly, is probably the multiplicity of effects on other
body systems.
The greatest challenge for public health is to develop effective preventive
measures, recognizing that BMI > 25 kg/m2 before the age of 20 years is a
very strong predictor of obesity and ill health in adulthood.
Publication Types: Review Review, Tutorial PMID: 10997648

http://konstanza.ingentaselect.com/vl=15182686/cl=12/nw=1/rpsv/cgi-bin/cgi?body=\
linker&ini=nlm&reqidx=issn=0007-1145vl=83%20Suppl%201is=yr=2000mn=Marpg=S103
free full text

Br J Nutr. 2000 Mar; 83 Suppl 1: S103-11.
Is long-term weight loss possible?
Lean ME. mej.lean@...
Department of Human Nutrition, University of Glasgow.

Any intervention which causes negative energy balance is guaranteed to be
efficacious in producing weight loss, which will continue while there is
negative energy balance or be maintained as long as the new energy balance
is maintained.
In clinical practice compliance is rarely 100% so the efficiency of even the
most efficacious treatment is usually low.
However, recent evidence-based guidelines have recognized the clinical
benefits of moderate (5-10%) weight loss, which is achievable using a
variety of interventions.
Long-term studies of 'weight loss' are, in reality, combinations of weight
loss (usually completed in 1-6 months) followed by variable weight
maintenance, set in the context of progressive adult weight gain in an
obesogenic environment.
Few studies have adopted specific and separate strategies for weight loss
and weight maintenance.
Meta-analyses conducted by non-expert methodologists have failed to
recognize these distinctions, and have criticized the available research
without understanding the different needs of studies with weight change as
the outcome variable, which require randomized controlled trials (RCT), and
those with weight loss as the treatment, intended to improve metabolic or
biomedical outcome measures.
An RCT design is inapplicable to studies of biomedical end points (e.g.
cardiac risk factors) when weight loss is the treatment.
Because fixed weight loss cannot be prescribed there is always a range of
weight changes in any study, and single-sample studies with regression
analysis provide the best design.
An RCT study design does not give useful information about clinical value as
the control group is always 'treated' to some extent.
Placebo- (or control)-subtracted differences are misleading because in an
RCT all subjects recruited to active treatment, including non-responders,
are continued on treatment for the full duration of the study.
In routine clinical practice, treatments are changed in the light of early
experience as a therapeutic trial to optimize the results for each
individual, and audit is required to evaluate 'long term weight loss'.
Publication Types: Review Review, Tutorial PMID: 10889800

http://diabetes.diabetesjournals.org/cgi/reprint/48/1/176 free full text

Diabetes. 1999 Jan; 48(1): 176-81.
Dietary flavonols protect diabetic human lymphocytes against oxidative
damage to DNA.
Lean ME, mej.lean@...
Noroozi M, Mostafa Noroozi
Kelly IE, Irene E. Kelly
Burns J, Jennifer Burns MD [ Glasgow Royal Infirmary, Dept of Medicine
for the Elderly: Dr Jacqueline Taylor. Dr Peter Langhorne, Prof David Stott,
Dr Jennifer Burns. Dept of Radiology
burns.jennifer@... ]
Talwar D, Dinesh Talwar fax 44-0141-553-1703
dtalwar@... Sattar N, Naveed Sattar MD Dr Naveed Sattar,
Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow
G31 2ER, Scotland, UK. E-mail nsattar@...
Crozier A., Alan Crozier A.Crozier@...
http://www.gla.ac.uk/departments/humannutrition/staff/staff3.html
Department of Human Nutrition, Glasgow Royal Infirmary, University of
Glasgow, UK. Research in Plant Foods and Nutrition
FACTORS INFLUENCING THE POLYPHENOL CONTENT OF RED WINE
An investigation to determine the effect of location, climate, variety and
vinification technique on the polyphenol content of red wines

Diabetic patients have reduced antioxidant defenses and suffer from an
increased risk of free radical-mediated diseases such as coronary heart
disease. Epidemiological evidence has suggested that antioxidant dietary
flavonoids may protect against heart disease, but a biological effect has
yet to be demonstrated directly in humans.
In this study, 10 stable type 2 diabetic patients were treated for 2 weeks
on a low-flavonol diet and for 2 weeks on the same diet supplemented with
76-110 mg of flavonols (mostly quercetin) provided by 400 g of onions (and
tomato sauce) and six cups of tea daily.
Freshly collected lymphocytes were subjected to standard oxidative challenge
with hydrogen peroxide, and DNA damage was measured by single-cell gel
electrophoresis.
Fasting plasma flavonol concentrations (measured by high-performance liquid
chromatography) were 5.6 +/- 2.9 ng/ml on the low-flavonol diet and
increased 12-fold to 72.1 +/- 15.8 ng/ml on the high-flavonol diet (P <
0.001).
Oxidative damage to lymphocyte DNA was
220 +/- 12 on an arbitrary scale of 0-400 U on the low-flavonol diet and
192 +/- 14 on the high-flavonol diet (P = 0.037).
This decrease was not accounted for by any change in the measurements of
diabetic control (fasting plasma glucose or fructosamine) or by any change
in the plasma levels of known antioxidants, including vitamin C,
carotenoids, alpha-tocopherol, urate, albumin, and bilirubin.
In conclusion, we have shown a biological effect of potential medical
importance that appears to be associated with the absorption of dietary
flavonols. PMID: 9892240
***************************************************************

http://www.ajcn.org/cgi/reprint/67/6/1210 free full text

Am J Clin Nutr. 1998 Jun; 67(6): 1210-8.
Effects of flavonoids and vitamin C on oxidative DNA damage to human
lymphocytes.
Noroozi M, Mostafa Noroozi
Angerson WJ, Wilson J. Angerson
Lean ME. Michael E.J. Lean
Department of Human Nutrition, Glasgow University, Royal Infirmary, United
Kingdom.

This study assessed the antioxidant potencies of several widespread dietary
flavonoids across a range of concentrations and compared with vitamin C as a
positive control.
The antioxidant effects of pretreatment with flavonoids and vitamin C, at
standardized concentrations (7.6, 23.2, 93, and 279.4 micromol/L), on oxygen
radical-generated DNA damage from hydrogen peroxide (100 micromol/L) in
human lymphocytes were examined by using the single-cell gel electrophoresis
assay (comet assay).
Pretreatment with all flavonoids and vitamin C produced dose-dependent
reductions in oxidative DNA damage.
At a concentration of 279 micromol/L, they were ranked in decreasing order
of potency as follows: luteolin (9% of damage from unopposed hydrogen
peroxide), myricetin (10%),
quercetin (22%),
kaempferol (32%),
quercitrin (quercetin-3-L-rhamnoside) (45%),
apigenin (59%),
quercetin-3-glucoside (62%),
rutin (quercetin-3-beta-D-rutinoside) (82%), and
vitamin C (78%).
The protective effect of vitamin C against DNA damage at this concentration
was significantly less than that of all the flavonoids except apigenin,
quercetin-3-glucoside, and rutin.
The ranking was similar with estimated ED50 (concentration to produce 50%
protection) values.
The protective effect of quercetin and vitamin C at a concentration of 23.2
micromol/L was found to be additive (quercetin: 71% of maximal DNA damage
from unopposed hydrogen peroxide; vitamin C: 83%; both in combination: 62%).
These data suggest that the free flavonoids are more protective than the
conjugated flavonoids (eg, quercetin compared with its conjugate
quercetin-3-glucoside, P < 0.001).
Data are also consistent with the hypothesis that antioxidant activity of
free flavonoids is related to the number and position of hydroxyl groups.
Publication Types: Clinical Trial Randomized Controlled Trial PMID:
9625095
***************************************************************

http://diabetes.diabetesjournals.org/cgi/reprint/48/1/176

Public Health Nutr. 2004 Apr; 7(2): 337-43.
Eating habits, beliefs, attitudes and knowledge among health professionals
regarding the links between obesity, nutrition and health.
Hankey CR, c.r.hankey@...
Eley S, [ Department of Applied Social Science, University of Stirling,
Stirling, UK. susan.eley@... ]
Leslie WS, w.s.leslie@...
Hunter CM, [ Colgate-Palmolive Company Technology Center, Piscataway, New
Jersey, USA. ]
Lean ME.
University of Glasgow Department of Human Nutrition, Queen Elizabeth
Building, Royal Infirmary, Glasgow G31 2ER, UK.

OBJECTIVE: To document knowledge, attitudes, beliefs and eating habits of
health professionals with respect to obesity, nutrition and weight
management.
DESIGN: A self-complete questionnaire postal survey.
SETTING: Primary care and dietetic practice in Scotland.
SUBJECTS: A systematic stratified sample of 2290 subjects incorporated
general practitioners (n=1400), practice nurses (n=613) and all practising
dietitians (n=360) who were members of the British Dietetic Association.
RESULTS: The overall response rate was 65%. All professionals showed a clear
understanding of nutrition and health.
Understanding of obesity as a disease and of the effectiveness of weight
management using low-energy diets was limited.
Below 10% had carried out audit to determine the incidence of obesity and
overweight, and most were uncertain about their own effectiveness in
delivering weight management advice.
CONCLUSION: This study confirms that health professionals have some
knowledge of nutrition and weight management but are unclear how to deliver
effective weight management advice.
Further training is justified to ensure the effective provision of
nutritional advice to patients. PMID: 15003142
****************************************************************

Compend Contin Educ Dent. 2003 Sep; 24(9 Suppl): 29-33; quiz 43.
Clinical comparison of Colgate Total Advanced Fresh vs a commercially
available fluoride breath-freshening toothpaste in reducing breath odor
overnight: a multiple-use study.
Niles HP, Hunter CM, Vazquez J, Williams MI, Cummins D.
Colgate-Palmolive Company Technology Center, Piscataway, New Jersey, USA.

The objective of this randomized, crossover study was to compare the
effectiveness of Colgate Total Advanced Fresh toothpaste to a commercially
available breath-freshening dentifrice containing fluoride for its ability
to reduce volatile sulfur compounds (VSC) responsible for breath odor
overnight.
The study followed a two-treatment, two-period crossover design. Subjects
were given a test product, along with a soft-bristled toothbrush, and
instructed to brush their teeth for 1 minute, twice daily (once in the
morning and the evening) using the assigned dentifrice for 7 consecutive
days.
After their evening brushing on the seventh day, subjects reported to the
testing facility without oral hygiene, eating, or drinking for the overnight
evaluation.
After a washout period, subjects repeated the same regimen, now using the
other test product.
The levels of breath VSC were evaluated instrumentally using a gas
chromatograph equipped with a flame photometric detector.
Publication Types: Clinical Trial Randomized Controlled Trial PMID:
14692210
****************************************************************

From: "Gary Chase" <Gary.Chase@...>
To: <rmforall@...>
Subject: Nurse' Health Study
Date: Friday, October 01, 2004 12:42 PM

Dear Mr. Murray:

I received your voicemail today about the Nurses' Health Study.
I'm sorry that I'm not really the best person to contact about
this, but I can tell you who you should get in touch with.

For more information about the necessary procedures to request
permission to work with NHS data, please contact Carol Leighton,
the assistant to the Principal Investigator, Graham Coldtiz.

She can be reached at carol.leighton@...

Hope that helps!

Gary Chase Project Manager Nurses' Health Study
***************************************************************

Graham A. Coldtiz, Department of Epidemiology, Harvard School of Public
Health, Boston, MA, USA; Channing Laboratory, Department of Medicine,
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA;
Channing Laboratory, Cancer Causes and Control, 181 Longwood Avenue, Boston,
MA 02115, USA; Ph.: +1-617-525-2258/2279; Fax: +1-617-525-2008;
graham.colditz@...; carol.leighton@...

Phone: (617) 525-2754 Fax: (617) 525-2008
Web Site: http://www.yourcancerrisk.harvard.edu
Contact Person: Carol Leighton
Roundtable Representative: Graham Colditz, MD
***************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1114
review of sweeteners 2004, Weihrauch MR, Diehl V: formaldehyde from 11%
methanol component of aspartame, methanol in dark wines and liquors,
fermentation of fruits in colon, also smoke, new buildings, furniture,
drapes, carpets, personal products: available database from Harvard Nurses'
Health Study II of 91,249 women in 1991-1999: Murray 2004.09.18 rmforall

Rich Murray, MA Room For All rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-501-2298

http://groups.yahoo.com/group/aspartameNM/messages
133 members, 1,117 posts in a public searchable archive

2004.09.17 This review by an unqualified, earnest medical layman, aims at
providing simple information from recent mainstream research on the toxicity
of formaldehyde. Here are a few summary remarks, backed up by the body of
this post.

http://groups.yahoo.com/group/aspartameNM/message/1094
the 11% methanol component of aspartame becomes formaldehyde, now ruled a
carcinogen by WHO International Agency for Research on Cancer: Murray
2004.06.16 rmforall

Methanol toxicity results from the inevitable conversion within hours of
much of it into formaldehyde and then formic acid, both potent, cumulative
toxins that affect every tissue, and that in long-term chronic exposure are
a major cause of hypersensitivity to formaldehyde and other chemicals.

About the same amount of methanol exists as an impurity, about one part in
ten thousand, in dark wines and liquors, stated by experts to be the major
cause of the infamous "morning after" hangover: "thirst, headache, fatigue,
nausea, sweating, tremor, remorse, and anxiety that hangover sufferers
report...." Also, dizziness is common, along with vision and eye problems,
irritability, impaired memory, "brain fog", aching joints and body pains,
flushed skin.

Jones AW (1987) found next-morning hangover from red wine with
100 to 150 mg methanol
(9.5% w/v ethanol; 100 mg/l methanol = 0.01%, one part in ten thousand).

Fully 11% of aspartame is methanol -- 1,120 mg aspartame in 2 L diet soda,
almost six 12-oz cans, gives 123 mg methanol (wood alcohol) -- the same
amount that produces hangover from red wine.

"Between a quarter and a half of drinkers claim not to experience hangover
symptoms despite having been intoxicated. (three citations)" This
indicates a remarkable range of individual vulnerability to formaldehyde and
formic acid exposure.

Other strong formaldehyde sources are tobacco and wood smoke, and the
particleboard and new furniture, carpet, and drapes especially concentrated
in mobile homes. Many personal care products contain formaldehyde; for
instance, leather shoes can cause foot dermatitis.

Similar levels of methanol, and its inevitable products in the human body,
formaldehyde and formic acid, can also ensue from fermentation of fruit
pectins in the colon.

The wide range of individual variability and the multitude of long-term,
low-level sources renders statistical studies difficult. It is commonsense
to consider seriously the multitudes of case reports of long-term heavy
users who become aspartame reactors, and to focus research on the actual
complex toxic biochemistry for long-term heavy exposure in vulnerable
people.

An available huge database exists in the Harvard Nurses' Health Study II.
The diabetes analysis included 91,249 women free of diabetes and other major
chronic diseases at baseline in 1991.
The weight change analysis included 51,603 women for whom complete dietary
information and body weight were ascertained in 1991, 1995, and 1999.

There were three questions on diet soft drinks
("low-calorie cola with caffeine,"
"low-calorie caffeine-free cola,"
and "other low-calorie beverages").

We summed the intake of single items to create a total of sugar-sweetened
soft drink, diet soft drink, and fruit juice consumption.

The 9 possible responses, ranging from "never" to "6 or more times per day,"
were aggregated into 4 categories
(<1 drink per month, 1-4 drinks per month, 2-6 drinks per week, and 1 drink
per day).

Similar questionnaires were used to collect dietary information in 1995 and
1999.

The data for "6 or more times per day", rather than being averaged out with
lower levels of use, should be studied for correlations with heavy alcohol
use, high use of fruit, tobacco and wood smoke, mobile homes, other
formaldehyde sources, MSG, carbon monoxide, VOCs, pesticides, heavy metals,
and the many typical symptoms for hangovers and aspartame reactors:
headaches, mental illnesses, seizures, dementia, accidents, crimes, suicide,
infertility, miscarriages, birth defects, autism, asthma, sudden infant
death syndrome, diabetes, cerebral palsy, allergies, Multiple Chemical
Sensitivity, Multiple Sclerosis, Fibromyalgia, Chronic Fatigue Syndrome,
Attention Deficit Disorder, arthritis, dermatitis, thyroid diseases, liver
diseases, obesity, heart diseases, stroke, cancers, vision problems,
addictions, as well as any protective effects of folic acid, which
facilitates the elimination of formaldehyde.

This database might well be fully available and immediately searchable to
test these associations.

The automated Comet assay, fast, sensitive, and inexpensive, is a standard
for assessment of DNA damage in any stored blood and tissue samples:

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 2003.01.01 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. Methanol is the only component of aspartame that can lead
to DNA damage. ]
**************************************************************

http://annonc.oupjournals.org/cgi/content/abstract/15/10/1460
Annals of Oncology 2004; 15(10): 1460-1465; doi:10.1093/annonc/mdh256
Articles by Weihrauch, M. R.
Articles by Diehl, V.
© 2004 European Society for Medical Oncology

Review

Artificial sweeteners-do they bear a carcinogenic risk?
M. R. Weihrauch* and V. Diehl v.diehl@...
Department of Internal Medicine I of the University of Cologne, Cologne,
Germany
* Correspondence to: Dr M. R. Weihrauch, Immunologisches Labor Haus 16,
Uniklinik Koeln, Joseph-Stelzmann-Strasse 9, 50924 Koeln, Germany. Tel:
+49-221-4784488 Fax: +49-221-4785912 martin.weihrauch@...

Artificial sweeteners are added to a wide variety of food, drinks, drugs and
hygiene products.
Since their introduction, the mass media have reported about potential
cancer risks, which has contributed to undermine the public's sense of
security.
It can be assumed that every citizen of Western countries uses artificial
sweeteners, knowingly or not.
A cancer-inducing activity of one of these substances would mean a health
risk to an entire population.
We performed several PubMed searches of the National Library of Medicine for
articles in English about artificial sweeteners.
These articles included 'first generation' sweeteners such as saccharin,
cyclamate and aspartame, as well as 'new generation' sweeteners such as
acesulfame-K, sucralose, alitame and neotame.
Epidemiological studies in humans did not find the bladder cancer-inducing
effects of saccharin and cyclamate that had been reported from animal
studies in rats. Despite some rather unscientific assumptions, there is no
evidence that aspartame is carcinogenic.
Case-control studies showed an elevated relative risk of 1.3 for heavy
artificial sweetener use (no specific substances specified) of >1.7 g/day.
For new generation sweeteners, it is too early to establish any
epidemiological evidence about possible carcinogenic risks.
As many artificial sweeteners are combined in today's products, the
carcinogenic risk of a single substance is difficult to assess.
However, according to the current literature, the possible risk of
artificial sweeteners to induce cancer seems to be negligible. PMID:
15367404
Key words: aspartame, cancer, cyclamate, saccharin, sweeteners
**************************************************************

Med Klin (Munich). 2001 Nov 15;96(11):670-5.
Erratum in:
Med Klin 2002 Mar 15;97(3):173.
[Artificial sweeteners--are they potentially carcinogenic?] [Article in
German]
Weihrauch MR, Diehl V, Bohlen H. martin.weihrauch@...

Klinik I fur Innere Medizin, Universitat zu Koln.

BACKGROUND: Artificial sweeteners have rapidly evolved over the last 20
years and are added to a broad variety of food, drinks, drugs, and hygiene
products.
Since their introduction, especially mass media have reported about
potential cancer risks, which has attributed to undermine the people's sense
of security.
It can be assumed that every citizen of the western countries is using
artificial sweeteners--knowingly or not.
A cancer-inducing activity of one of these substances would mean a health
risk to an entire population.
STUDIES: This article gives an overview about the most important
publications dealing with the cancerogenic potential of artificial
sweeteners.
Publication Types: Review Review, Tutorial PMID: 11760654
**************************************************************

http://groups.yahoo.com/group/aspartameNM/message/1088
Murray, full plain text & critique:
chronic aspartame in rats affects memory, brain cholinergic receptors, and
brain chemistry, Christian B, McConnaughey M et al, 2004 May:
2004.06.05 rmforall

Pharmacol Biochem Behav. 2004 May; 78(1): 121-7.
Chronic aspartame affects T-maze performance, brain cholinergic receptors
and Na(+),K(+)-ATPase in rats.
Christian B, McConnaughey K, Bethea E, Brantley S, Coffey A, Hammond L,
Harrell S, Metcalf K, Muehlenbein D, Spruill W, Brinson L, McConnaughey M.
Department of Pharmacology, Brody School of Medicine, East Carolina
University, Greenville, NC 27858, USA;
North Carolina School of Science and Mathematics, Durham, NC 27811.
http://www.ecu.edu/pharmacology/faculty/mcconnaughey.html
Mona M. McConnaughey, Ph.D. Research Assistant Professor
Department: PHARMACOLOGY & TOXICOLOGY
Office: Brody Medical Science 6E-120A 252-744-2756
MCCONNAUGHEYM@...

This study demonstrated that chronic aspartame consumption in rats can lead
to altered T-maze performance and increased muscarinic cholinergic receptor
densities in certain brain regions.
Control and treated rats were trained in a T-maze to a particular side and
then periodically tested to see how well they retained the learned response.
Rats that had received aspartame (250 mg/kg/day) in the drinking water for 3
or 4 months showed a significant increase in time to reach the reward in the
T-maze, suggesting a possible effect on memory due to the artificial
sweetener. Using [(3)H]quinuclidinyl benzilate (QNB) (1 nM) to label
muscarinic cholinergic receptors and atropine (10(-6) M) to determine
nonspecific binding in whole-brain preparations,
aspartame-treated rats showed a 31% increase in receptor numbers when
compared to controls.
In aspartame-treated rats, there was a significant increase in muscarinic
receptor densities in the frontal cortex, midcortex, posterior cortex,
hippocampus, hypothalamus and cerebellum of 80%, 60%, 61%, 65%,
66% and 60%, respectively.
The midbrain was the only area where preparations from aspartame-treated
rats showed a significant increase in Na(+),K(+)-ATPase activity.
It can be concluded from these data that long-term consumption of aspartame
can affect T-maze performance in rats and alter receptor densities or
enzymes in brain. PMID: 15159141

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 2004.03.30 rmforall [ 150 KB ]

"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. ]
**************************************************************

For instance, here is a bonanza of information about the health of probably
hundreds of nurses who use 6 or more cans daily of diet soda -- they have
also stored blood and tissue samples from their immense pool of subjects.

Could a team be organized to explore their aspartame and alcohol data,
and even any correlations with high consumption of fruits and fruit juices,
as well as alcohol?

They may have information about how many live in mobile homes, a well known
formaldehyde exposure.

"In 1991, the mailed questionnaire included a 133-item semiquantitative food
frequency questionnaire.

Women were asked how often they had consumed a commonly used unit or portion
size of each food on average over the previous year, including 3 items on
consumption of sugar-sweetened soft drinks
("Coke, Pepsi, or other cola with sugar,"
"caffeine-free Coke, Pepsi, or other cola with sugar,"
and "other carbonated beverages with sugar"),
4 items on fruit juice
("apple juice," "orange juice," "grapefruit juice," and "other juice"),
1 item on fruit punch,

and 3 items on diet soft drinks
("low-calorie cola with caffeine,"
"low-calorie caffeine-free cola,"
and "other low-calorie beverages").

We summed the intake of single items to create a total of sugar-sweetened
soft drink, diet soft drink, and fruit juice consumption.

The 9 possible responses, ranging from "never" to "6 or more times per day,"
were aggregated into 4 categories
(<1 drink per month, 1-4 drinks per month, 2-6 drinks per week, and 1 drink
per day).

Similar questionnaires were used to collect dietary information in 1995 and
1999.

Nutrient intakes were computed by multiplying the frequency response by the
nutrient content of the specified portion sizes."

http://jama.ama-assn.org/cgi/content/full/292/8/927 free full text

JAMA. 2004 Aug 25; 292(8): 927-34.
Comment in:
JAMA. 2004 Aug 25; 292(8): 978-9.
Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in
young and middle-aged women.
Schulze MB, Manson JE, Ludwig DS, Colditz GA, Stampfer MJ, Willett WC,
Hu FB. mschulze@...
Department of Nutrition, Harvard School of Public Health, Boston, Mass, USA.

CONTEXT: Sugar-sweetened beverages like soft drinks and fruit punches
contain large amounts of readily absorbable sugars and
may contribute to weight gain and an increased risk of type 2 diabetes,
but these relationships have been minimally addressed in adults.
OBJECTIVE: To examine the association between consumption of sugar-sweetened
beverages and weight change and risk of type 2 diabetes in women. DESIGN,
SETTING, AND PARTICIPANTS: Prospective cohort analyses conducted from 1991
to 1999 among women in the Nurses' Health Study II.
The diabetes analysis included 91,249 women free of diabetes and other major
chronic diseases at baseline in 1991.
The weight change analysis included 51,603 women for whom complete dietary
information and body weight were ascertained in 1991, 1995, and 1999.
We identified 741 incident cases of confirmed type 2 diabetes during 716,300
person-years of follow-up.
MAIN OUTCOME MEASURES: Weight gain and incidence of type 2 diabetes.
RESULTS: Those with stable consumption patterns had no difference in weight
gain, but weight gain over a 4-year period was highest among women who
increased their sugar-sweetened soft drink consumption from 1 or fewer
drinks per week to 1 or more drinks per day (multivariate-adjusted means,
4.69 kg for 1991 to 1995 and 4.20 kg for 1995 to 1999) and
was smallest among women who decreased their intake (1.34 and 0.15 kg for
the 2 periods, respectively) after adjusting for lifestyle and dietary
confounders. Increased consumption of fruit punch was also associated with
greater weight gain compared with decreased consumption.
After adjustment for potential confounders, women consuming 1 or more
sugar-sweetened soft drinks per day had a relative risk [RR] of type 2
diabetes of 1.83 (95% confidence interval [CI], 1.42-2.36; P<.001 for trend)
compared with those who consumed less than 1 of these beverages per month.
Similarly, consumption of fruit punch was associated with increased diabetes
risk (RR for > or =1 drink per day compared with <1 drink per month, 2.00;
95% CI, 1.33-3.03; P =.001).
CONCLUSION: Higher consumption of sugar-sweetened beverages
is associated with a greater magnitude of weight gain and an increased risk
for development of type 2 diabetes in women, possibly by providing excessive
calories and large amounts of rapidly absorbable sugars. PMID: 15328324

Vol. 292 No. 8, August 25, 2004
Sugar-Sweetened Beverages, Weight Gain, and Incidence of Type 2 Diabetes in
Young and Middle-Aged Women
Matthias B. Schulze, DrPH; mschulze@...
JoAnn E. Manson, MD; jmanson@...
David S. Ludwig, MD; david.ludwig@...
Graham A. Colditz, MD; graham.colditz@...
Meir J. Stampfer, MD; mstampfe@...
Walter C. Willett, MD; WWillett@...
Frank B. Hu, MD frank.hu@...

JAMA. 2004; 292: 927-934.

"Dr Stampfer and colleagues have demonstrated a marked protective effect,
both in women and men, of alcohol in reducing the risk of coronary heart
disease. In women, however, alcohol appears to be associated with an
increase in risk of breast cancer, but this may be mitigated by dietary
folate."

Alcohol, methanol, formaldehyde, and formic acid in low levels may act as
antibiotics, eliminating bacteria that may be involved in heart disease.

However, formaldehyde is now officially declared to be a carcinogen.
Adaquate folate facilitates the faster elimination of formaldehyde from the
body.

http://www.hsph.harvard.edu/facres/stmpfr.html

Meir Stampfer
Professor of Nutrition and Epidemiology; Chair, Department of Epidemiology
Departments of Epidemiology and Nutrition

Department of Epidemiology
Kresge Building 9th Floor 677 Huntington Avenue Boston, MA 02115
Phone: 617-432-6477 Fax: 617-566-7805
Email: mstampfe@...
Education
Dr.P.H., 1985, Harvard School of Public Health
M.D., 1977, New York University School of Medicine

Research Interests
Dr Stampfer's research program is broadly concerned with the etiology of
chronic diseases, with particular focus on nutrition, cancer, and
cardiovascular disease. With colleagues in the Departments of Epidemiology
and Nutrition at Harvard School of Public Health, and at Channing Laboratory
and the Division of Preventive Medicine at Brigham and Women's Hospital, Dr
Stampfer is closely involved in four large prospective cohort studies:
Nurses' Health Study I (N = 121,700), Health Professionals Follow-Up Study
(N = 51,259), Physicians' Health Studies I and II (N = 22,071), and Nurses'
Health Study II (N = 116,678).
In each of these studies, participants are
surveyed every two years to gather information on diet, smoking, physical
activity, medications, health screening behavior, and other variables. We
also ascertain the new occurrence of cancer, cardiovascular disease, and
other serious illnesses, including diabetes, fractures, kidney stones, and
pre-cancerous lesions.
In addition, Dr Stampfer leads seven NIH-funded
projects to assess nutritional and biochemical markers of cancer risk among
the 15,000 blood samples collected as part of the Physicians' Health Study.
In his work in the cohort studies, he directs grants addressing the causes
of prostate cancer and colon cancer.
Dr Stampfer and colleagues have
demonstrated a marked protective effect, both in women and men, of alcohol
in reducing the risk of coronary heart disease. In women, however, alcohol
appears to be associated with an increase in risk of breast cancer, but this
may be mitigated by dietary folate.
Recent analyses have shown women who adhere to five simple guidelines (no
smoking, not obese, physically active, consume moderate alcohol, and have a
good diet) are at 80% lower risk for coronary disease.
Analyses of the Physicians' Health Study blood samples
have yielded some surprising results: insulin-like growth factor (IGF-1)
emerged as the most powerful risk factor for prostate cancer yet identified;
it is also strongly linked to colon cancer risk. All of these large-scale
studies are continuing.
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