Rich Murray: Simmons: Gold: Schiffman: Spiers:
aspartame toxicity 6.4.1 rmforall

N Engl J Med 1987 Nov 5;317(19):1181-5
Aspartame and susceptibility to headache.
Schiffman SS, Buckley CE 3d, Sampson HA,
Massey EW, Baraniuk JN, Follett JV, Warwick ZS
Department of Psychiatry, Duke University, Durham, N.C. 27710.

Dr. Susan S. Schiffman Dept. of Psychiatry Duke University
www.duke edu sss@... 919-684-3303, 660-5657.
She has over 100 obviously competent experimental studies and
reviews since 1971 in PubMed. Her major field is the deterioration
of smell and taste in seniors and AIDS patients from exposure to
drugs, chemicals, and pollutants-- one wonders if she ever considered
the effects of aspartame, since smell and tase impairment are known to
result from exposure to aspartame or formaldehyde.

"Loss of taste" is one of 90 symptoms from many case reports of
aspartame toxicity, summarized in:
Department of Health and Human Services. "Report on All Adverse
Reactions in the Adverse Reaction Monitoring System." (February 25
and 28, 1994).

Abstract (Schiffman et al, 1987):
We performed a double-blind crossover trial of challenges with 30 mg of
aspartame per kilogram of body weight or placebo in 40 subjects who
reported having headaches repeatedly after consuming products
containing aspartame. The incidence rate
of headache after aspartame (35 percent)
was not significantly different from that after placebo (45 percent)
(P less than 0.50). No serious reactions were observed, and the
incidence of symptoms other than headache following aspartame was also
equivalent to that after placebo. No treatment-related effects were
detected in vital signs, blood pressure, or plasma concentrations of
cortisol, insulin, glucagon, histamine, epinephrine, or norepinephrine.
Most of the subjects were well educated and overweight and had a family
or personal history of allergic reactions. The subjects who had
headaches had lower plasma concentrations of
norepinephrine (P less than 0.0002) and epinephrine (P less than 0.02)
just before the development of headache.
We conclude that in this population, aspartame is no more
likely to produce headache than placebo. PMID: 3657889, UI: 88014077

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

http://www.holisticmed.com/aspartame/abuse/migraine.html :

"Scientific Abuse in Migraine/Headache Research Related to Aspartame":

"Other industry researchers have cited this study as evidence that
aspartame does not induce headaches (Butchko 1994, Leon 1989, Moser
1994). In addition, Yost (1989) claimed that aspartame is not more
likely to cause headache than placebo. Tollefson (1992) of the FDA
cited this Schiffman study as evidence that aspartame does not cause
headaches. (The Tollefson review was discussed in detail in the
Seizure Research Abuse section).

"What these researchers fail to mention is that the Schiffman (1987)
research is useless because of major design flaws. It is also
particularly troubling that none of the above-mentioned authors
cited the Koehler (1988) double-blind study!

"Before we discuss the major flaws of the Schiffman study, I will
present some background information. The study was partially funded
by Monsanto/NutraSweet and conducted at the Searle Center at Duke
University. (G.D. Searle is owned by Monsanto.) Susan Schiffman
performed her research at the "Searle Center" at Duke University.
The Searle Center is under the guidance of William Anlyan, a former
G.D. Searle director. Schiffman is a former General Foods and G.D.
Searle consultant. The FDA helped design the study protocol.
[Gordon 1987, page 500 of US Senate 1987; Shapiro 1987, page 403
of US Senate 1987].)

"Schiffman (1987) major flaws:

1.The aspartame was given for only one day.

2.The aspartame was given in encapsulated form which would lower the
toxicity by eliminating the sudden absorption of the excitotoxic amino
acid and methanol (Stegink 1987). The absorption of the excitotoxin is
gradual, somewhat closer to what happens when ingesting food. The
methanol is absorbed more slowly and that may significantly reduce
toxicity as happens when food in the stomach slows methanol absorption
(Posner 1975).

3.There was no baseline frequency of headaches determined before
administering aspartame or placebo.

"It is very important to note the main distinction between the Koehler
(1988) study and the Schiffman (1987) study. While both studies used
capsules, which would be expected to significantly reduce aspartame
toxicity, and both studies used subjects who claimed to have headaches
from aspartame, the Koehler (1988) study administered aspartame for
four weeks, while the Schiffman (1987) study administered the
aspartame for only one day!

"When one examines the double-blind studies funded by the aspartame
industry, a pattern develops. Industry-supported research on subjects
who have reported serious reactions to aspartame is almost always
one day long and the aspartame is administered in capsules (e.g.,
Hertelendy 1993, Rowen 1995, Schiffman 1987). Industry-supported
research that lasts several weeks is usually performed on individuals
that might be expected to experience adverse reactions after at least
several months of aspartame use (e.g., Shaywitz 1994) or on individuals
even less susceptible to short-term aspartame toxicity, but where more
sensitive neurological tests were conducted (e.g., Spiers 1998). The
longer (but still relatively short) industry-supported research
(3-6 months) usually uses healthy subjects who would likely only
experience serious adverse reactions after many months or several
years of aspartame use (e.g., Leon 1989, Trefz 1994). While the length
of the study is not the only flaw in these industry-sponsored studies,
there appears to be an obvious pattern of exceptionally short studies
used on more susceptible subjects. It would appear that the
manufacturer funds research with protocol designs virtually guaranteed
to find no adverse reactions!" [end of Gold quote]

Am J Clin Nutr 1998 Sep; 68(3): 531-7
Aspartame: neuropsychologic and neurophysiologic evaluation of acute
and chronic effects.
Spiers PA, Sabounjian L, Reiner A, Myers DK, Schomer DL
Clinical Research Center, Massachusetts Institute of Technology,
Cambridge 02139, USA.
Paul A. Spiers paspiers@... 617-253-6797
and 978-887-6220 Neurological Associates
Donald L. Schomer, M.D., Assc. Prof. Neurology, Beth Israel Deaconess
Medical Center, Harvard Medical Sch., dschomer@...,
617-667-3999

This study, done on or before 1993, was described in an abstract in
1993: then Richard J. Wurtman, Ph.D., Director of the CRC, was
listed as an author, but not in 1998. It was paid for by NutraSweet
Co. It used 48 healthy college students, half male and half female in
each group of 24, high-dose and low-dose aspartame, also tested with
placebo and sucrose, who took 20 days each of daily aspartame, sucrose,
or placebo, and were tested clinically on the morning of the 20th day,
before the last dose. The study is summarized by Schomer, Spiers, and
Sabounjian on pages 225-31 in "The Clinical Evaluation of a Food
Additive: Assessment of Aspartame," 1996, CRC Press, 308 pages, Ed. by
Tschanz C, Butchko H, Stargel WW, Kotsonis FN, all employees of
Monsanto/NutraSweet.

High-dose, 45, and low-dose, 15 mg/kg daily, groups had 24 subjects
each. The results showed that the total number of headaches was about
the same for low dose, sucrose, and placebo, at 11,14, and 11, but only
4 headaches for the 24 high-dose subjects in 20 days. The probability
of this is not given.
The numbers for fatigue were 3, 4, 2, and 1, for nausea 1, 3, 4, and 1,

for acne 1, 4, 3, and 2. For these 4 symptoms,
the most common reported, the high-dose group is far less than sucrose
or placebo. This indicates that some sort of confounding processes
were indeed operating, and that the study is therefore meaningless,
unless we are to start proclaiming aspartame as the newest aspirin.

Wouldn't a few students simply stop taking pills, if they thought it
caused headache, and wouldn't they also start taking regular aspirin?
Wouldn't a few students continue their favored diet drinks and foods?
Wouldn't exposure to MSG, claimed by many researchers to have similar
toxic biochemistry and symptoms, also confound the results? Only a few
malfunctions like this suffice to eliminate statistical significance in
a group of only 24.

"Complaints of adverse experiences were recorded in blinded fashion."
It is not clear whether a symptom log was kept on a daily basis, or
if symptoms were discussed only at day 10 and 20. The scientific
community should have access to the actual raw data for daily symptoms
for each subject.

"We were clearly able to distinguish the subjects in the high-dose
aspartame group when they received the aspartame treatment because
they had significantly elevated fasting plasma phenylalanine
concentrations (Figures 3 and 4)..." This was about a 30% higher value
at 85 minutes after the 3 PM dose on day 10, compared to placebo or
sucrose. Is this kind of rise seen from consumption of phenylalanine
in ordinary foods?

Since aspartame and its products, methanol, formaldehyde, and aspartic
acid are cumulative toxins, we would expect symptoms to increase over
the 20 days, and to continue afterwards when the subjects were given
sucrose and placebo. Since vulnerability varies greatly, we would
expect a few subjects to be providing most of the symptoms. It might
be illuminating to have the raw data on each of the subjects.

Moreover, when aspartame is given in capsules and at meals, then it
is released gradually into the body, along with foods that mitigate
its effects, while diet soda, the main source of aspartame, allows
aspartame to be absorbed quickly, often with little food. In many
cases, symptoms may not develop until after months and years of daily
exposure, as in the case of tobacco. Finally, the sample of 24 in
the high-dose group allows us to infer, at best, even if the study
had inpecably consistent results, that the incidence of harm within 3
weeks in healthy college students is perhaps less than 5 or 10% at
the 95% confidence level.
***********************************************************************

Rich Murray Room For All rmforall@...
1943 Otowi Road Santa Fe, NM 87505 505-986-9103

M.I.T. (physics and history, BA, 1964), Boston U. Graduate School
(psychology, MA, 1967): As a concerned layman, I want to clarify the
aspartame toxicity debate.

http://groups.yahoo.com/group/aspartameNM/message/618
long 40K summary

Excellent 5-page review by H.J. Roberts in "Townsend Letter",
Jan 2000, "Aspartame (NutraSweet) Addiction"
http://www.dorway.com/tldaddic.html http://www.sunsentpress.com/
H.J. Roberts, M.D. HRRobertsmd@... sunsentpress@...
Sunshine Sentinel Press 6708 Pamela Lane West Palm Beach, FL 33405
800-814-9800 561-588-7628 561-547-8008 fax
1038 page text "Aspartame Disease: An Ignored Epidemic"
published May 30 2001 $ 85.00 postpaid data from 1200 cases
http://www.aspartameispoison.com/contents.html 34 chapters

Here is research in 1998 at a very low level of aspartame ingestion,
10 mg/kg, for rats, which have a much greater tolerance for aspartame
than humans. The same level for humans would be about 1 or 2 mg/kg.
Many headache studies in humans used doses of about 30 mg/kg daily.
A daily dose of 2100mg aspartame, about 4 L diet soda, used in many
experimental tests on humans, supplies 210mg methanol into the body.
Many cases report a typical serious symptom syndrome at this level.

This report shows that aspartame causes binding of methanol's product,
formaldehyde, a potent, cumulative toxin, into tissues.

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

Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas,
Sr. Jordi Virgili, X. Remesar, Dr. Jose Antonio Fernandez-Lopez,
Dr. Maria Alemany Fac. Biologia
Tel.: (93)4021521, Fax: (93)4021559
alemany@... bioq@...
rafecas@... remesar@...
Sra. Carme Trocho Tel.: (93)4021544, Fax: (93)4021559
***********************************************************************

www.catalystmagazine.com/inthemix.callingfornominations.shtml
Kenna Simmons, Editor Catalyst magazine 3379 Peachtree Rd.,
Suite 300 Atlanta, GA 30326 Tel: 404-888-0555
ksimmons@...

http://www.nutrasweet.com/infocenter/consumer/otherssay/fibronewsletter.asp

The Facts About Aspartame "Disease"
by Kenna Simmons

Maybe a well-meaning friend sent you the e-mail letter by "Nancy
Markle" linking aspartame to fibromyalgia — as well as to
lupus, multiple sclerosis (MS), Alzheimer's disease, diabetes, Gulf
War Syndrome and seizures. This e-mail, actually written by a
woman named Betty Martini who is an anti-aspartame advocate,
has been circulating since 1995 but recently experienced a
renewed lease on life.

The claims made in the e-mail aren't supported by scientific
evidence. The primary claim is that aspartame, an artificial
sweetener marketed as NutraSweet and found in many diet drinks,
causes "methanol toxicity" and leads to systemic lupus
erythematosus (SLE) and MS. Aspartame does contain methanol
(when digested, it yields about 10 percent methanol by weight),
along with the amino acids aspartic acid and phenylalanine.
However, many fruits and vegetables also contain methanol; in
fact, there is more methanol in a glass of tomato juice than in a diet
drink. In the body, methanol is converted to formic acid and then to
carbon dioxide and water, which are quickly eliminated. The body
doesn't treat these substances any differently, whether they come
from fruit or aspartame.

Another claim made in the e-mail letter is that aspartame is
responsible for an increase in the number of brain tumors in the
U.S. A 1996 report in the Journal of Neuropathology and
Experimental Neurology (Vol. 55, No. 11) did note an increase in
the incidence of malignant brain tumors and suggested that
aspartame might be a "promising candidate" for the increase. (The
report did not include a study of aspartame.) But data from the
National Cancer Institute's public database on cancer incidence in
the United States indicates that the number of brain tumors
reported had been on the rise from 1973 to 1985, possibly due to
improved methods of detection. Aspartame was approved by the
FDA as a food additive in 1981, 8 years after the increase in brain
tumors began. Since 1985, the numbers have remained steady,
and actually decreased from 1991 to 1993.

A recent double-blinded study in the American Journal of Clinical
Nutrition (Vol. 68, No. 3) reported that even large doses of
aspartame had no effect on people's health. For one month,
participants ingested no aspartame at all. Over the next three
months, for one month each, they ingested placebo, sucrose
(natural sugar), and 45 mg/kg of aspartame — the equivalent
of about 17 12-ounce diet drinks per day for male subjects or 14
diet drinks for female subjects. All participants underwent physical
and psychological testing. Participants showed no changes in
physiology, brain activity, mood, memory or behavior. Equal
numbers of headaches, fatigue and nausea were reported by the
subjects when they took placebo and sucrose as when they took
aspartame.

To put these dosages into context, the FDA establishes an
Acceptable Daily Intake (ADI) for most food additives. For
aspartame, the ADI is 50 mg/kg; that's about 20 12-oz. diet soft
drinks or 97 packets of Equal for the average 150-pound adult. (A
12-oz. diet drink contains about 200 mg of aspartame.) However,
the average person's consumption of aspartame is about two to
three mg/kg, or about four percent of the ADI. The ADI includes a
large margin of safety — it is often 100 times greater than
the level found to cause no effects in animals — so even if
you exceed the ADI, you probably still will not ingest a dangerous
amount of aspartame.

There are some people for whom aspartame intake must be
monitored: those with a rare genetic disease called phenylketonuria
(PKU), who cannot properly metabolize phenylalanine, a
component of aspartame. People with PKU must strictly limit the
amount of phenylalanine they consume, whether it's from
aspartame or foods such as meat, nuts and milk.

Studies that investigated whether aspartame can cause
headaches in some people have conflicting answers: A 1987
study reported in the New England Journal of Medicine (Vol. 317,
No. 19) found that aspartame was no more likely to cause
headaches than placebo, whereas a 1994 study published in
Neurology (Vol. 44, No. 10) concluded that it appeared some
people were susceptible to headaches caused by aspartame. If
you think you are susceptible to "aspartame headaches," try
eliminating it from your diet and see if your headaches decrease.

Other Claims Made by the "Nancy Markle" Letter
There is no way to examine her statement that aspartame causes
fibromyalgia because "Nancy Markle" does not try to support that
claim in her letter. The e-mail has been so frequently discussed in
fibromyalgia support groups and Internet news groups, however,
that we have provided below examinations of the letter's more
extensive claims about aspartame and other conditions to shed
some light on the kind of logic that characterizes the letter in
general.


"The EPA announced that there was an epidemic of multiple
sclerosis and systemic lupus." First of all, the Environmental
Protection Agency doesn't track disease prevalance; the
National Institutes of Health (NIH) and the Centers for
Disease Control and Prevention (CDC) do. Second, there is
no epidemic; the numbers of people diagnosed with MS or
lupus have remained relatively constant.
"Methanol toxicity mimics multiple sclerosis; people were
being diagnosed with multiple sclerosis in error." According
to David Squillacote, MD, senior medical advisor to the
Multiple Sclerosis Foundation, "there is no evidence that
aspartame in any way causes, provokes, mimics or
worsens MS." In addition, Dr. Squillacote calls the claims
regarding how methanol is metabolized "wildly inaccurate,"
noting that volunteers have taken 600 mg of aspartame
each hour for eight hours without any rise in their methanol
levels.
"When we get people off the aspartame, those with
systemic lupus usually become asymptomatic." According to
Evelyn Hess, MD, chair of the Lupus Foundation of America
Medical Council, there is no proof that aspartame causes or
worsens lupus.
"Methanol in the aspartame converts to formaldehyde in the
retina of the eye." High levels of methanol in the blood can
cause vision impairment and blindness. But remember, the
aspartame in a diet drink contains less methanol than a
glass of fruit juice, and study participants have taken large
amounts of aspartame without experiencing any visual
problems.
"Aspartame changes the brain's chemistry. It is the reason
for severe seizures." A randomized, double-blinded,
placebo-controlled study reported in the journal Epilepsia
(Vol. 36, No. 3) found that dosages of 50 mg/kg of
aspartame were no more likely to cause seizures than
placebo in people who had reported their seizures were
due to aspartame.
"This drug also causes birth defects." According to a 1988
article in the Journal of Reproductive Medicine, aspartame,
when consumed within FDA guidelines, is safe for pregnant
women and does not expose the fetus to danger.
"Aspartame is especially deadly for diabetics." According to
a statement by the American Diabetes Association, "There
is no credible scientific evidence linking aspartame to any
health-related problems for people with diabetes."
"Aspartame Disease is partially the cause to what is behind
some of the mystery of the Dessert (sic) Storm health
problems." So far, researchers haven't been able to
discover what causes Gulf War Syndrome, though some
theories center on exposure to toxic gas during the Gulf
War. A 1997 congressional investigation indicated that
possible causes might include exposure to pesticides or
smoke from oil well fires. No evidence exists to suggest that
aspartame has anything to do with Gulf War Syndrome, and
the aspartame intake of our troops was never monitored.


A Conspiracy Theory
The e-mail claims that a conspiracy between Monsanto (maker of
NutraSweet and Equal), the American Diabetes Association, the
American Dietetic Association, the FDA, and various researchers
is responsible for a cover-up of the truth about aspartame.
Conspiracy theorists dismiss studies because they are funded by
grants from Monsanto. However, in clinical trials and other studies,
it is common for the maker of a drug or food additive to provide a
grant to independent researchers. The studies mentioned above
were published in peer-reviewed journals, which means that
editors with no connection to Monsanto reviewed the studies and
found the methods used for research acceptable.

Searle, the pharmaceutical subsidiary of Monsanto, is one of the
Arthritis Foundation's several corporate sponsors. These sponsors
donate money to help further the mission of the Foundation through
supporting research and educational programs, but the Foundation
does not endorse any organization's commercial products or
services. Like all educational material created by the Foundation,
this newsletter is reviewed by medical professionals and experts
whose editorial and medical opinions are independent of the views
of any corporate sponsor. A list of medical advisory board
members appears on page 2.

Fibromyalgia Wellness Letter, April 1999, Vol. 2, Issue 2. A
publication of the Arthritis Foundation
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