Compiled By Rich Murray, MA
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Posted: 11 June 2005
Three independent double-blind experiments on aspartame and headache in 1988, 1993, 1994

These links provide detailed summaries of studies in 1988, 1993, and 1994 that are not funded by the aspartame industry, are experimental studies published in mainstream peer-reviewed journals, and that largely agree with each other in showing a very high percentage of people with headache and other typical symptoms for a daily use of aspartame in capsules for test periods of 1 to 4 weeks.

As far as I know, never in three decades has any study in humans also made specific biochemical tests to show how the three components, which are rather independently and freely absorbed via the GI tract, accumulate in and affect specific cells and tissues in people who display headache and the other commonly reported symptoms, and who prima facie are in more vulnerable groups. So, basically, despite the 786 studies since 1973 listed for aspartame in PubMed, there is no adequate information on the basic biochemical realities of the disposition and toxicity of the three components in humans.

To quickly do a few such exhaustive workups on a few people would be extremely valuable as pilot studies. Perhaps insurance could pay the costs for diagnostic tests, measurements, and imaging.

In view of the urgency of dealing with long-neglected public heath problems of largely unknown nature and scope, the results of such pilot studies might best be put in full detail on the Net, with an open, moderated forum for civil debate and feedback.

The results would illuminate cases of chronic, long-term exposure to methanol (formaldehyde, formic acid) from many other sources: medical education and practice, morticians, dark wines and liquors, tobacco, wood smoke, vehicle exhaust, new buildings and mobile homes, and degradation by bacteria in the colon of pectins from fruits and vegetables.

Short review: research on aspartame (methanol, formaldehyde, formic acid) toxicity
Research on aspartame (methanol, formaldehyde, formic acid) toxicity
Methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full plain text, 2001: Substantial sources are degradation of fruit pectins, liquors, aspartame, smoke

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.
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
Alan Glaros

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

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: 2001.06.04 Two double-blind studies