Compiled By Rich Murray, MA
Room For All
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Santa Fe, New Mexico 87505 USA
Telephone: 505-501-2298
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Posted: 25 May 2005
Short review: research on aspartame (methanol, formaldehyde, formic acid)
Research on aspartame (methanol, formaldehyde, formic acid) toxicity: Murray

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). If 30% of the methanol is turned into formaldehyde, the amount of formaldehyde is 18 times the USA EPA limit for daily formaldehyde in drinking water, 2 mg in 2 L water.

Aspartame (NutraSweet, Equal, Canderel, E951), after eight years of controversy, was suddenly and capriciously approved by a new FDA commissioner, Arthur Hull Hayes, Jr, just appointed by President Reagan, a pharmacologist who had been in office less than three months and had little background in food additives, in July 1981, overturning the vote of his own Scientific Board of Inquiry.

Aspartame is made of phenylalanine (50% by weight) and aspartic acid (39%), both ordinary amino acids, bound loosely together by methanol (wood alcohol, 11%). The readily released methanol from aspartame is within hours turned by the liver into formaldehyde and then formic acid, both potent, cumulative toxins.

A team in a Searle Co. lab, led by J.A. Oppermann proved that 30% of the methanol in aspartame fed to rats remained, indubitably as toxic products of formaldehyde and formic acid in all tissues (1973, 1976).
Methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full plain text, 2001: Substantial sources are degradation of fruit pectins, liquors, aspartame, smoke
Aspartame puts formaldehyde adducts into tissues, Part 1/2 full text, Trocho & Alemany 1998.06.26

This was confirmed by an expert team at the University of Barcelona (Trocho, Alemany et al, 1998):

"...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...These are indeed extremely high levels for adducts of formaldehyde, a substance responsible for chronic deleterious effects (33), that has also been considered carcinogenic (33,47)."
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation carcinogenicity results Dec 2002: Soffritti:

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal tract to become free methyl alcohol, which is metabolized in the liver to formaldehyde, formic acid, and CO2. (11)" Medinsky MA & Dorman DC. 1994; Assessing risks of low-level methanol exposure. CIIT Act. 14: 1-7. Ann N Y Acad Sci. 2002 Dec; 982: 87-105.

Results of long-term experimental studies on the carcinogenicity of formaldehyde and acetaldehyde in rats. M. Soffritti et al. Cancer Research Center, European Ramazzini Foundation for Oncology and Environmental Sciences, Bologna, Italy.
Eight depressed people react strongly to aspartame, Prof. Ralph G. Walton, MD, 1993 double-blind study, full text:

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.

Many scientific studies and case histories report:
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval: Turner:
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, full plain text & critique: chronic aspartame in rats affects memory, brain cholinergic receptors, and brain chemistry, Christian B, McConnaughey M et al, 2004 May
Eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV Belsito, Nov 2003
Continuing aspartame debate in British Medical Journal, John Biffra, Bob Dowling, Nick Finer, Ian J Gordon
Politicians and celebrities hooked on diet sodas (aspartame) Gives 585,000 websites for "aspartame" , with the top 7 of 10 listings Being anti-aspartame, while lists 786 aspartame items.
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
RTM: Smith, Terpening, Schmidt, Gums: full text: aspartame, MSG, fibromyalgia

Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following Discontinuation of Dietary Excitotoxins.

The Annals of Pharmacotherapy 2001; 35(6): 702-706.

Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.

BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is often difficult to treat effectively.

CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome for two to 17 years are described.

All had undergone multiple treatment modalities with limited success. All had complete, or nearly complete, resolution of their symptoms within months after eliminating monosodium glutamate (MSG) or MSG plus aspartame from their diet.

All patients were women with multiple comorbidities prior to elimination of MSG.

All have had recurrence of symptoms whenever MSG is ingested.

Siegfried O. Schmidt, MD
Asst. Clinical Prof.
Community Health and Family Medicine
University of Florida
Gainesville, FL

Shands Hospital West Oak Clinic
Gainesville, FL 32608-3629
Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde adducts in rats

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."

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 919-684-3303, 660-5657
RTP ties to industry criticized by CSPI: Murray: 2002.12.09
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

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

Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research
Blumenthall & Vance: aspartame chewing gum headaches Nov 1997: Murray 2002.07.28

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.

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]

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.

We determined the genotoxicity of 39 chemicals currently in use as food additives. They fell into six categories-dyes, color fixatives and preservatives, preservatives, antioxidants, fungicides, and sweeteners.

We tested groups of four male ddY mice once orally with each additive at up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow 3 and 24 h after treatment.

Of all the additives, dyes were the most genotoxic. Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal induced dose-related DNA damage in the glandular stomach, colon and/or urinary bladder. All seven dyes induced DNA damage in the gastrointestinal organs at a low dose (10 or 100mg/kg).

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
24 recent formaldehyde toxicity [Comet assay] reports
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in mice: Sasaki YF & Tsuda S Aug 2002

[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.]
Genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor; sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2000 [A detailed look at the data] Original documents and long reviews of flaws in aspartame toxicity research
Samuels: Strong: Roberts: Gold: flaws in double-blind studies re aspartame and MSG toxicity

"Survey of aspartame studies: correlation of outcome and funding sources," 1998, unpublished:

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
Gold: Koehler: Walton: Van Den Eeden: Leon:
Aspartame toxicity: Four double-blind studies

Headache 1988 Feb; 28(1): 10-4
The effect of aspartame on migraine headache.
Koehler SM, Glaros A PMID: 3277925, UI: 88138777

Shirley M. Koehler, PhD 904-858-7651
Alan Glaros 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 significance 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

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

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
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 strong increase in headaches from the first week of daily aspartame 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: Two double-blind studies