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continuing aspartame debate in British Medical Journal, John Biffra, Bob Dowling, Nick Finer, Ian J Gordon: Murray 2005.02.09 rmforall

Rich Murray rmforall at att.net
Sat Feb 12 21:12:11 EST 2005

continuing aspartame debate in British Medical Journal, John Biffra, Bob
Dowling, Nick Finer, Ian J Gordon: Murray 2005.02.09 rmforall


BMJ  2005; 330: 309-310 (5 February), doi:10.1136/bmj.330.7486.309-a


Aspartame and its effects on health
Independently funded studies have found potential for adverse effects

EDITOR -- Lean and Hankey's editorial on the effects of aspartame and health
gives this artificial sweetener a clean bill of health. (1)

 However, it seems they have ignored or dismissed a wealth of evidence,
which shows that aspartame can provoke a wide range of symptoms including
depression (2)  and headaches. (3, 4)

Other studies (a total of 91) that attest to aspartame's potential for harm
can be found in an online review of peer reviewed literature. (5)

This review is particularly worrying as it shows that, although 100% of
industry funded (either whole or in part) studies conclude that aspartame is
safe, 92% of independently funded studies have found that aspartame has the
potential for adverse effects.

Image: Molecular structure of aspartame
Credit: www.lefinnosis.net

Also, while Lean and Hankey speculate on the potential of aspartame to bring
about weight loss, their assessment is largely theoretical (based on the
potential for the replacement of sugar with aspartame to bring about caloric

Despite two decades of use in the human diet, not one single, double blind,
placebo controlled study that supports aspartame's supposed weight loss
effects has been published.

Lean and Hankey endorse the use of aspartame in the diet, but the facts are
that this synthetic chemical's "benefits" are unproved, and a considerable
body of evidence exists that shows it has very real potential for harm.

The glaring disparity in results from industry funded and independently
funded research is clearly of considerable concern.

Lean and Hankey say that the public needs protection from "misleading"
websites warning of the hazards of aspartame.

It seems that what the members of the public (and the medical profession)
really need protecting from is editorials lacking in balance and

John Briffa, general practitioner
London N6 5ED     DrJBriffa at aol.com

Competing interests: None declared.


Michael Lean, Catherine Hankey. Aspartame and its effects on health. BMJ
2004;329: 755-6. (2 October.)[Free Full Text]

Walton RG, Hudak R, Green-Waite RJ. Adverse reactions to aspartame:
double-blind challenge in patients from a vulnerable population. Biol
Psychiatry 1993;34(1-2): 13-7.[CrossRef][ISI][Medline]

Van Den Eeden SK, Koepsell TD, Longstreth Jr WT, van Belle G, Daling JR,
McKnight B. Aspartame ingestion and headaches: a randomized, crossover
trial. Neurology 1994;44: 1787-93.[Abstract]

Lipton RB, Newman LC, Cohen JS, Solomon S. Aspartame as a dietary trigger of
headache. Headache 1989;29(2): 90-2.[ISI][Medline]

Walton RG. Survey of aspartame studies: correlation of outcome and funding
sources. www.dorway.com/peerrev.html (accessed 18 Nov 2004).

Related Article:
Aspartame and its effects on health Michael E J Lean and Catherine R Hankey
BMJ 2004 329: 755-756. [Extract] [Full Text]

Rapid Responses:
[ http://bmj.bmjjournals.com/cgi/eletter-submit/330/7486/309-a  Submit your
Rapid Response ]

Aspartame and its effect on health Bob Dowling bmj.com, 8 Feb 2005 [Full

Aspartame and its effect on health 8 February 2005
Bob Dowling, Consultant Anaesthetist
Wye Valley Nuffield Hospital, Venns Lane, Hereford HR1 UK

Send response to journal:  Re: Aspartame and its effect on health

With reference to the recent Editorial and correspondence, Aspartame gives
me various forms of extrasystoles including bigemini.

Briefly, I discovered this in 1983 while training for body building
competitions where loss of subcutaneous fat is necessary to show muscular
For some 12 weeks my pre-contest diet included "diet" coke in place of beer.
I assumed the cardiac irregularities from which I began to suffer could be
due to caffeine in the Coca Cola and substituted mineral water.
The cardiac irregularities stopped within 24 hours.

About five years ago, again training for competition, I began taking a well
known protein powder supplement.
After two days extrasystoles began and on reading the label I found
Aspartame to be an ingredient.
I stopped the powder and had no more extrasystoles.

The following stories are possibly relevant:

1. An overweight locum SHO had to go off duty following an episode of
cardiac irregularity.
On talking to him afterwards he told me that he had begun taking a large
amount of Candarel in place of sugar in an attempt to lose weight.
On stopping Candarel no further problems.

2. A local racing cyclist was having frequent "palpitations" several times a
week. This man is very fit.
He saw his GP during one particular attack and was immediately referred to
the local Casualty Department as a suspected coronary thrombosis.
By the time the patient was seen the arrhythmia had stopped and the ECG was
I met this man 13 months ago and he told me of his problem.
It transpired that to keep his weight down to racing fitness he was drinking
several cans of "diet" drinks a day.
He was advised to stop this and since then he has continued to train hard
and has not had a single further episode of arrhythmia of which he is aware.

3. At least three theatre staff with whom I have worked over the last three
years (and the mother of one of them) have had similar histories of
All of them had been drinking "diet" preparations.
On stopping them, again no further pulse irregularities.

A theatre assistant was likewise complaining of palpitations.
It transpired that she was chewing "diet" chewing gum containing Aspartame.
By stopping this the palpitations stopped.

Aspartame is in very many foods and drinks, it is even in some brands of
effervescent Vitamin C in spite of the label proclaiming "no added flavours
or colourings".
I am very well aware that my evidence is merely based on personal experience
and anecdotal episodes but I am convinced that in some people this is an
unrecognised cause of cardiac irregularity.
Is there anybody out there who has had similar experiences, or have I opened
eyes to a possible cause of a frequent complaint?

Competing interests: None declared

© 2005 BMJ Publishing Group Ltd


BMJ  2005;330:310 (5 February), doi:10.1136/bmj.330.7486.310-a


Aspartame and its effects on health
Approach seems simplistic in electronic responses to editorial

EDITOR -- Lean and Hankey's editorial provoked excited responses on bmj.com
from nutritionists, wellness experts, and journalists that showed an often
simplistic and selective approach to evidence. (1 )

Mercola talks about "flooding the brain" with amino acids, presupposing that
aspartame causes excessive rises in plasma concentrations of phenylalanine
that then cross the blood-brain barrier.
Plasma phenylalanine rises to 80-120 mmol/l after a protein meal such as a
glass of the "natural substance" milk, about the same as after a dose of 34
mg aspartame per kg body weight (about 28 canned drinks sweetened with
aspartame consumed at once); current consumption data show that average
daily intake is less than 1% of this and maximum intake less than 10%. (2)

Briffa thinks that aspartame metabolism produces methanol toxicity.
According to the US Food and Drug Administration, to cause toxicity in
humans, 200-500 mg methanol per kg body weight is needed to produce
sufficient amounts of its metabolite, formate (federal register 1984).
This corresponds to drinking 600-1700 cans of diet soft drink at once, an
amount not achieved after a dose of 200 mg aspartame per kg body weight. (3)

In long term studies formate production is balanced by excretion, so blood
concentrations of formate do not change.

Briffa quotes data on formaldehyde accumulation in animals when little
aspartame was ingested but not a study in primates that describes the normal
conversion of formaldehyde to formate and its inclusion in the one-carbon
folate pool, eventually forming S-adenosylmethionine (4)

The appearance of around 1% of the radiolabelled carbon in protein, DNA, or
RNA could be explained by the rapid flux of carbon through
S-adenosylmethionine or other folate dependent reactions into these
molecules and tissues.

This flux reflects methanol from any source (fruit juice, pectin, or
aspartame) and is normal biochemistry, not a toxic event. (4)

The European Commission's Scientific Committee on Food recently reviewed
both science and clinical evidence and gives an update on the safety of
aspartame. (5)

Nick Finer, consultant in obesity medicine
Addenbrooke's Hospital, Cambridge CB2 2QQ   nf237 at medschl.cam.ac.uk

Competing interests: NF is medical adviser to Ajinomoto.


Electronic responses. Aspartame and its effects on health. bmj.com 2004.
http://bmj.bmjjournals.com/cgi/eletters/329/7469/755 (accessed 27 Jan 2005).

French Food Safety Agency. Assessment report. Opinion on a possible link
between the exposition [sic] to aspartame and the incidence of brain tumours
in humans. Maisons-Alfort: French Food Safety Agency, 2002.

www.aspartame.org/pdf/AFSSA-Eng.pdf (accessed 28 Dec 2004).

Stegink LD, Filer LJ. Effects of aspartame ingestion on plasma aspartate,
phenylalanine and methanol concentrations in potentially sensitive
populations. In: Tschanz C, Butchko HH, Stargel WW, Kotsonis FN, eds. The
clinical evaluation of a food additive. Assessment of aspartame. Boca Raton,
FL: CRC Press, 1996: 87-113.

Tephly TR. Comments on the purported generation of formaldehyde and adduct
formation from the sweetener aspartame. Life Sci 1999;65:

Commission of the European Communities, Health and Consumer Protection
Directorate-General. Opinion of the Scientific Committee on Food: update on
the safety of aspartame. Brussels, 4 December 2002. (SCF/CS/ADD/EDUL/222
Final.) www.food.gov.uk/multimedia/pdfs/aspartameopinion.pdf (accessed 28
Dec 2004).


BMJ  2005;330:310 (5 February), doi:10.1136/bmj.330.7486.310


Aspartame and its effects on health
Readers may prefer balanced and impartial editorials

EDITOR -- Why did the editorial on aspartame by Lean and Hankey go to such
lengths to vindicate the substance without any balanced review of the
numerous papers on its side effects? (1)

An editorial should impartially review all aspects of the current
information on a subject and leave it to the reader to decide or research
further. The rapid responses by Mercola, Briffa, and Hull clearly state the
other side of the coin. (2)

I am particularly concerned because of personal experience, having had a
severe episode of fortification spectra after trying aspartame
sweeteners -- the like of which I have never had in 37 years of having

What could the effect be in those with serious cerebrovascular disease?

I would like to see another editorial to balance the one by Lean and Hankey,
as too many reports of adverse effects exist for this to be dismissed as
hypochondriasis or people's resentment of food interference.

Ian J Gordon, physician in occupational medicine
Whiston Hospital, Merseyside L35 5DR   ijgord at tesco.net

Competing interests: None declared.

Lean M, Hankey C. Aspartame and its effects on health. BMJ 2004;329: 755-6.
(2 October.)[Free Full Text]

Electronic responses. Aspartame and its effects on health. bmj.com 2004
http://bmj.bmjjournals.com/cgi/eletters/329/7469/755 (accessed 19 Nov 2004).

Mark Gold, most recent of 14 Rapid Responses to Aspartame
and its effects on health, BMJ: Murray 2004.11.06 rmforall

8 more Rapid Responses to Aspartame and its effects on health, BMJ:
Murray 2004.10.18 rmforall

5 critical Rapid Responses to Aspartame and its effects on health, Michael E
J Lean and Catherine R Hankey,
BMJ 2004; 329: 755-756: Murray 2004.10.05 rmforall

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

Alcohol Clin Exp Res. 1997 Aug; 21(5): 939-43.
Endogenous production of methanol after the consumption of fruit.
Lindinger W, Taucher J, Jordan A, Hansel A, Vogel W.
Institut fur Ionenphysik, Leopold Franzens Universitat Innsbruck, Austria.

After the consumption of fruit, the concentration of methanol in the human
body increases by as much as an order of magnitude.
This is due to the degradation of natural pectin (which is esterified with
methyl alcohol) in the human colon.
In vivo tests performed by means of proton-transfer-reaction mass
spectrometry show that consumed pectin in either a pure form (10 to 15 g)
or a natural form (in 1 kg of apples) induces a significant increase of
methanol in the breath (and by inference in the blood) of humans.
The amount generated from pectin (0.4 to 1.4 g) [ 400 to 1400 mg ]
is approximately equivalent to the total daily endogenous production
(measured to be 0.3 to 0.6 g/day) [ 300 to 600 mg ]
or that obtained from 0.3 liters of 80-proof brandy
(calculated to be 0.5 g). [ 1667 mg methanol per liter of brandy ]
This dietary pectin may contribute to the development
of nonalcoholic cirrhosis of the liver. PMID: 9267548

Alcohol Clin Exp Res. 1995 Oct; 19(5): 1147-50.
Methanol in human breath.
Taucher J, Lagg A, Hansel A, Vogel W, Lindinger W.
Institut fur Ionenphysik, Universitat Innsbruck, Austria.

Using proton transfer reaction-mass spectrometry for trace gas analysis of
the human breath, the concentrations of methanol and ethanol have been
measured for various test persons consuming alcoholic beverages and various
amounts of fruits, respectively.
The methanol concentrations increased from a natural (physiological) level
of approximately 0.4 ppm up to approximately 2 ppm a few hours after eating
about 1/2 kg of fruits,
and about the same concentration was reached after drinking of 100 ml brandy
containing 24% volume of ethanol and 0.19% volume of methanol.
[ 24 ml = 61 g ethanol, and 0.19 ml = 0.34 g = 340 mg methanol ]
PMID: 8561283

methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full
plain text, 2001: substantial sources are degradation of fruit pectins,
liquors, aspartame, smoke: Murray 2005.02.02 rmforall

"That substantial amounts of methanol metabolites or by-products are
retained for a long time is verified by Horton et al. (1992) who estimated
that 18 h following an iv injection of 100 mg/kg of 14C-methanol in male
Fischer-344 rats, only 57% of the dose was eliminated from the body.

>From the data of Dorman et al. (1994) and Medinsky et al. (1997), it can
further be calculated that 48 h following the start of a 2-h inhalation
exposure to 900 ppm of 14C-methanol vapors in female cynomolgus monkeys,
only 23% of the absorbed 14C-methanol was eliminated from the body.

These findings are corroborated by the data of Heck et al. (1983) showing
that 40% of a 14C-formaldehyde inhalation dose remained in the body 70 h

"Exposure to methanol also results from the consumption of certain
foodstuffs (fruits, fruit juices, certain vegetables, aspartame sweetener,
roasted coffee, honey) and alcoholic beverages (Health Effects Institute,
1987; Jacobsen et al., 1988)."

"However, the severe toxic effects are usually associated with the
production and accumulation of formic acid, which causes metabolic acidosis
and visual impairment that can lead to blindness and death at blood
concentrations of methanol above 31 mmol/l (Røe, 1982; Tephly and McMartin,
1984; U.S. DHHS, 1993).

Although the acute toxic effects of methanol in humans are well documented,
little is known about the chronic effects of low exposure doses, which are
of interest in view of the potential use of methanol as an engine fuel and
current use as a solvent and chemical intermediate.

Gestational exposure studies in pregnant rodents (mice and rats) have also
shown that high methanol inhalation exposures (5000 or 10,000 ppm and more,
7 h/day during days 6 or 7 to 15 of gestation) can induce birth defects
(Bolon et al., 1993; IPCS, 1997; Nelson et al., 1985)."

"The corresponding average elimination half-life of absorbed methanol
through metabolism to formaldehyde was estimated to be 1.3, 0.7-3.2, and 1.7

"Inversely, in monkeys and in humans, a larger fraction of body burden of
formaldehyde is rapidly transferred to a long-term component.
The latter represents the formaldehyde that (directly or after oxidation to
formate) binds to various endogenous molecules..."

"Animal studies have reported that systemic methanol is eliminated mainly by
metabolism (70 to 97% of absorbed dose) and only a small fraction is
eliminated as unchanged methanol in urine and in the expired air (< 3-4%)
(Dorman et al., 1994; Horton et al., 1992).

Systemic methanol is extensively metabolized by liver alcohol dehydrogenase
and catalase-peroxidase enzymes to formaldehyde, which is in turn rapidly
oxidized to formic acid by formaldehyde dehydrogenase enzymes (Goodman and
Tephly, 1968; Heck et al., 1983; Røe, 1982; Tephly and McMartin, 1984).

Under physiological conditions, formic acid dissociates to formate and
hydrogen ions.

Current evidence indicates that, in rodents, methanol is converted mainly by
the catalase-peroxidase system whereas monkeys and humans metabolize
methanol mainly through the alcohol dehydrogenase system (Goodman and
Tephly, 1968; Tephly and McMartin, 1984).

Formaldehyde, as it is highly reactive, forms relatively stable adducts with
cellular constituents (Heck et al., 1983; Røe, 1982)."

"The whole body loads of methanol, formaldehyde, formate, and unobserved
by-products of formaldehyde metabolism were followed.

Since methanol distributes quite evenly in the total body water, detailed
compartmental representation of body tissue loads was not deemed necessary."

"According to model predictions, congruent with the data in the literature
(Dorman et al., 1994; Horton et al., 1992), a certain fraction of
formaldehyde is readily oxidized to formate, a major fraction of which is
rapidly converted to CO2 and exhaled, whereas a small fraction is excreted
as formic acid in urine.

However, fits to the available data in rats and monkeys of Horton et al.
(1992) and Dorman et al. (1994) show that, once formed, a substantial
fraction of formaldehyde is converted to unobserved forms.

This pathway contributes to a long-term unobserved compartment.

The latter, most plausibly, represents either the formaldehyde that
(directly or after oxidation to formate) binds to various endogenous
molecules (Heck et al., 1983; Røe, 1982)
or is incorporated in the tetrahydrofolic-acid-dependent one-carbon pathway
to become the building block of a number of synthetic pathways (Røe, 1982;
Tephly and McMartin, 1984).

That substantial amounts of methanol metabolites or by-products are retained
for a long time is verified by Horton et al. (1992) who estimated that 18 h
following an iv injection of 100 mg/kg of 14C-methanol in male Fischer-344
rats, only 57% of the dose was eliminated from the body.

>From the data of Dorman et al. (1994) and Medinsky et al. (1997), it can
further be calculated that 48 h following the start of a 2-h inhalation
exposure to 900 ppm of 14C-methanol vapors in female cynomolgus monkeys,
only 23% of the absorbed 14C-methanol was eliminated from the body.

These findings are corroborated by the data of Heck et al. (1983) showing
that 40% of a 14C-formaldehyde inhalation dose remained in the body 70 h

In the present study, the model proposed rests on acute exposure data, where
the time profiles of methanol and its metabolites were determined only over
short time periods (a maximum of 6 h of exposure and a maximum of 48 h

This does not allow observation of the slow release from the long-term

It is to be noted that most of the published studies on the detailed
disposition kinetics of methanol regard controlled short-term (iv injection
or continuous inhalation exposure over a few hours) methanol exposures in
rats, primates, and humans (Batterman et al., 1998; Damian and Raabe, 1996;
Dorman et al., 1994; Ferry et al., 1980; Fisher et al., 2000; Franzblau et
al., 1995; Horton et al., 1992; Jacobsen et al., 1988; Osterloh et al.,
1996; Pollack et al., 1993; Sedivec et al., 1981; Ward et al., 1995; Ward
and Pollack, 1996).

Experimental studies on the detailed time profiles following controlled
repeated exposures to methanol are lacking."

"Thus, in monkeys and plausibly humans, a much larger fraction of body
formaldehyde is rapidly converted to unobserved forms rather than passed on
to formate and eventually CO2."

"However, the volume of distribution of formate was larger than that of
methanol, which strongly suggests that formate distributes in body
constituents other than water, such as proteins.

The closeness of our simulations to the available experimental data on the
time course of formate blood concentrations is consistent with the volume of
distribution concept (i.e., rapid exchanges between the nonblood pool of
formate and blood formate)."

"Also, background concentrations of formate are subject to wide
interindividual variations (Baumann and Angerer, 1979; D'Alessandro et al.,
1994; Franzblau et al., 1995; Heinrich and Angerer, 1982; Lee et al., 1992;
Osterloh et al., 1996; Sedivec et al., 1981)."


Toxicological Sciences 64, 169-184 (2001)
Copyright © 2001 by the Society of Toxicology


A Biologically Based Dynamic Model for Predicting the Disposition of
Methanol and Its Metabolites in Animals and Humans

Michèle Bouchard *, #,1,   bouchmic at magellan.umontreal.ca

Robert C. Brunet, #   brunet at dms.umontreal.ca

Pierre-Olivier Droz, #

and Gaétan Carrier*   gaetan.carrier at umontreal.ca

* Department of Environmental and Occupational Health, Faculty of Medicine,
Université de Montréal, P.O. Box 6128, Main Station, Montréal, Québec,
Canada, H3C 3J7;

# Institut Universitaire romand de Santé au Travail, rue du Bugnon 19,
CH-1005, Lausanne, Switzerland, and

#  Département de Mathématiques et de Statistique and Centre de Recherches
Mathématiques, Faculté des arts et des sciences, Université de Montréal,
P.O. Box 6128, Main Station, Montréal, Québec, Canada, H3C 3J7

President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

faults in 1999 July EPA 468-page formaldehyde profile:
Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of Bialystok, Poland,
abstracts -- ethanol, methanol, formaldehyde, formic acid, acetaldehyde,
lipid peroxidation, green tea, aging, Lyme disease:
Murray 2004.08.08 rmforall

Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 2002.12.23 rmforall

A very detailed, highly credible account of the dubious approval process for
aspartame in July, 1981 is part of the just released two-hour documentary
"Sweet Misery,  A Poisoned World:  An Industry Case Study of a Food Supply
In Crisis" by Cori Brackett:   cori at soundandfuryproductions.com
http://www.soundandfuryproductions.com/  520-624-9710
2301 East Broadway, Suite 111  Tucson, AZ 85719

Aspartame Victims Support Group   Edward Bryant Holman, Chief Moderator
810  members, 18,073 posts in a public, searchable archive
http://www.presidiotex.com/aspartame/    bryanth at presidiotex.net

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

http://www.sweetpoison.com/ Janet Starr Hull, PhD, CN jshull at sweetpoison.com

Janet Starr Hull, who also had Graves disease in 1991, told Justin Dumais to
quit aspartame: Murray 2004.06.12 rmforall

http://www.aspartamesafety.com    marystod at airmail.net
Mary Nash Stoddard, Founder
Aspartame Consumer Safety Network and Pilot Hotline [1987-2004]
P.O. Box 2001  Frisco, TX 75034   1-214-387-4001   [ 25 miles N of Dallas ]

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

Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references

genotoxicity of aspartame in human lymphocytes 2004.07.29 full plain text,
Rencuzogullari E et al, Cukurova University, Adana, Turkey 2004 Aug: Murray
2004.11.06 rmforall

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

eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 3.30.4 rmforall   [ 150 KB ]

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

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 at brookshealth.org
Alan Glaros  glarosa at umkc.edu  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.

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 at aol.com

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 at dor.kaiser.org
Division of Research, Kaiser Permanente Medical Care Program
3505 Broadway, Oakland, CA 94611-5714

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:

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

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