From: Rich Murray [rmforall@att.net] Sent: Sunday, August 04, 2002 7:25 PM To: fdadockets@oc.fda.gov Subject: RTM: FDA: (Section B) Gold: Koehler: Walton: Van Den Eeden: Leon: aspartame toxicity 6.4.1 rmforall RTM: FDA: (Section B) Gold: Koehler: Walton: Van Den Eeden: Leon: aspartame toxicity 6.4.1 rmforall June 4 2001 Date: Sat, 12 Feb 2000 14:31:12 EST From: AndyCutler@aol.com To: rmforall@earthlink.net [minor editing by Rich Murray for comments and brevity] [If aspartame only causes a 1% incidence of headache, then] Probability of no event = 0.99. Do it twice and the probability of it NOT happening the first time AND it NOT happening the second time is 0.99 * 0.99 or 0.9801. Etc., etc. The probability of nothing happening after 35 trials is 0.99 ^ 35 = 0.7034. [RM: So, there is a 70% chance of missing it in 35 trials, if it has a 1% chance of occurence each trial. In 70 trials, there is 0.99 ^ 70 = .495 = 50% chance of missing it.] The probability of of it happening one or more times is 1 - 0.7034 = 0.2966 In order to have a 95% probability of observing an event that has a 1% chance of occurring, 298 trials are required. That is, the probability of the event not happening in any trial [at all in the whole series of 298 trials] is 0.99 ^ 298 = 0.05. You do have to use the more complete form of the binomial distribution if you want to calculate things like the probability the event occurs exactly 1 time. The form I used above, P ^ n, is the correct form for the event always occurring or never occurring. Since the probability of harm not occurring is 0.99, and we want to determine the number n for which the probability of harm not occurring in a group of n aspartame users is <0.500, we have 0.99 ^ n ~= 0.500 or n ~= log(0.500)/log(0.99) which ~= 69. So the aspartame consumer group must contain at least 69 people. To have a 95% chance that at least one has been harmed (a 5% chance that nobody was), we have n ~= log(0.05)/log(0.99) ~= 298. *********************************************************************** Date: Thu, 06 May 1999 08:15:25 +0200 From: Per Dalen To: Discussion of Fraud in Science Below I am forwarding an interesting off-list comment on my post of yesterday: From: AndyCutler@aol.com Date: Wed, 5 May 1999 17:34:20 EDT In a message dated 99-05-05 06:30:54 EDT, you write: >Of course, and this is probably the reason why smallish, >but controlled studies are loved by the >PR people of various producers of potentially >hazardous things. Repeating (or republishing) neat and "correctly >designed" studies of this kind is good practice from their point of >view, because it creates the impression that serious efforts are being >made to reveal any risks connected with their products. This is sheer >propaganda, because "safety" can never be established in this way. Even assuming that the study population has an equal incidence of the problem in question (college students are great since they tend to be healthier-- med students even more so), to have half a chance of finding something that has a 1% incidence, which is HUGE by public health standards, you have to use 69 subjects. Very few studies are that big-- and how many studies of 69 or more subjects have you seen that didn't exclude one or more of them for some undefined reason? [Murray: So, if aspartame harms only 1 of 100 people who use it, then in order to have a 50% chance of showing it, we would have to compare 69 users vs 69 non-users-- then there would be a 50% chance that the user group will have the 1 person harmed. That isn't great science, especially considering that there is a large background incidence of headaches.] You need to use 229 subjects to have a 90% chance of finding that 1% incidence problem. [So, to have a 90% chance of showing it is a non-chance effect, we would have to compare 229 users vs 229 non-users-- then there would be a 90% chance that the user group would have the 1 person harmed. In other words, there would be only a 10% chance that the non-user group might have the the 1 person harmed, if aspartame is actually harmful. This is far more users than most double-blind tests of aspartame, which use 12 to 50 subjects.] You need to use 298 subjects to have a 95% chance of finding that 1% incidence problem-- and "95% confidence" is the usual level of certainty medical research bozos cite in deciding whether to pay attention to a problem. Thus no study on aspartame containing less than 298 subjects (without any leaving the study) is valid for asserting that less than 1% of the population is having adverse effects from it. [About 200 million use aspartame in the USA. A 1% incidence of harm means 2 million cases. So, there has never been any experimental test of aspartame toxicity that eliminates the possibility that there are about 2 million people harmed in the USA, with reported symptoms ranging from headaches to seizures to brain tumors.] You need 458 subjects to have a 99% chance of finding that 1% incidence problem. You want 95% confidence for a 0.1% problem? E. g. that something like 5-10 thousand Swedes will fall over dead from drinking the stuff? That takes a study enrolling 2994 people ALL OF WHOM are accounted for as results at the end. Lots of universities aren't BIG enough to get that many students to enroll in a study like this! Per - maybe you should share this with your list? Putting some numbers to it often makes things more obvious. Per Dalen [More comments by Rich Murray] Think of all the things that can go wrong in the typical double-blind study, in which neither the subjects, often intelligent, rambunctious young healthy college students, nor the scientists are supposed to know which pill is the drug and which is the inert placebo. For one thing, the subjects are constantly exposed to aspartame in things like yogurt, chewing gum, and many medicines. All the subject has to do is to open or bite the capsule to find if it is inert or not, or just notice if he feels something from the pill or not. If he finds that he is taking the aspartame, and gets a headache, and happens to be getting, say $ 50 a day for the study, and the scientist seems to look grumpy when he tells about the headache, then the subject is motivated to pretend to take the aspartame, to pretend he doesn't get headaches, and to take aspirin every day. One subject like that is enough to invalidate the chance of proving with 95% confidence, with 298 subjects exposed to aspartame, that aspartame has a 1 in 100 incidence of harm. How much do you trust college students? And what about the scientists? Are they going to report results that put a quick end to their lavish funding by industry? Is the industry going to publish any negative findings? Isn't the industry going to praise, publish, and fund the teams that get the desired results? So all the furor for decades, testing aspartame and a host of other things with elaborate double-blind experimental studies is only proving that fundamental law of society: money talks.] Neuroepidemiology 1993;12(3):179-94 Epidemiology of migraine. Silberstein SD, Lipton RB Comprehensive Headache Center, Germantown Hospital and Medical Center, Philadelphia, Pa. Migraine epidemiology presents methodological challenges, partially simplified by the use of the new International Headache Society (IHS) Classification. Most previously published migraine studies were clinic-based, which introduces bias since less than 5% of migraineurs consult specialists. A series of population-based studies of migraine prevalence and incidence, based on the new operational IHS criteria, are now available and are reviewed, along with the migraine personality, comorbid psychiatric conditions and neuropsychological impairment. Migraine headaches are now divided into those with aura (classic migraine) and those without aura (common migraine). Headache occurs in about 91% of men and 96% of women, migraine occurs in about 6% of men and 18% of women (one-year prevalence). Migraine is most common in the third decade of life and in lower socioeconomic groups. It is associated with an increased prevalence of depression and panic attacks. PMID: 8272178, UI: 94097472 This raises more fundamental issues. If headache occurs in 91% of men and 96% of woman at least once a year, especially in the many subjects who are college-age, then, as is common knowledge, there is a great background incidence of headaches, making it even more dicey to test for the effects of aspartame, if the incidence of headache is 1% for aspartame users. Some of the studies here merely count together the percent of all subjects who report some headaches during up to 6 months of daily aspartame use, without reporting the actual total of headaches and the distribution in time of headaches for each subject. In most toxic processes, some people are far more vulnerable than others, and this vulnerability can change, decreasing due to developing tolerance, increasing if the toxin is cumulative. It is a public relations ploy, not science for the common welfare, to not present the actual specific raw data, and not give an adaquate analysis of whether certain subjects have the most symptoms, which symptoms cluster together, and which symptoms increase with time, along with foolproof tests that the test subjects are actually taking their doses, whether the subjects were actually avoiding aspartame in their daily diets, whether use of pain medications like aspirin increased, and, very fundamentally, ensuring that a complete symptom check list was recorded every day-- all failings in an often-cited study by Leon et al in 1989. But, first we review three studies that support one another in displaying the striking reality of high incidence of aspartame toxicity. 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 skoehler@brookshealth.org http://www.med.umich.edu/abcn/alpha/alpha-K.html#Koehler Alan Glaros glarosa@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. 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@aol.com 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@dor.kaiser.org 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. Safety of long-term large doses of aspartame Arthur S. Leon, Donald B. Hunninghake, Catherine Bell, David K. Rassin, Thomas R. Tephly Arch. Int. Med. October 1989 149(10), 2318-24. Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis. Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a randomized, double-blind, placebo-controlled, parallel-group design in 108 male and female volunteers aged 18 to 62 years. Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks. No persistent changes over time were noted in either group in vital signs; body weight; results of standard laboratory tests; fasting blood levels of aspartame's constituent amino acids (aspartic acid and phenylalanine), other amino acids, and methanol; or blood formate levels and 24-hour urinary excretion of formate. There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject. These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day. PMID: 2802896, UI: 90025598 Prof. Arthur S Leon leonx002@tc.umn.edu Kinesiology and Leisure Studies Division of Kinesiology, College of Education and Human Development 110 Cooke H 1900 University Ave SE Minneapolis, MN 55455 Room 100 CookeH 2061 1900 University Ave SE Minneapolis, MN 55455 Office Phone: +1 612-624-8271 Prof. Donald B. Hunninghake,MD hunni001@maroon.tc.umn.edu Department of Medicine, University of Minnesota, Minneapolis 55455, USA. Heart Disease Prevention Clinic 179 V C R C 401 E River Rd Minneapolis, MN 55455 Box 192 Mayo 8192 420 Delaware Minneapolis, MN 55455 Office Phone: +1 612-625-4447 Thomas R. Tephly 319-335-7979 thomas-tephly@uiowa.edu ttephly@blue.weeg.uiowa.edu Department of Pharmacology The University of Iowa, Iowa City 52242, USA. Here we have a detailed critique by Mark D. Gold of misleading research on aspartame, in which Leon and Tephly were frequent participants in many of studies, all funded by the aspartame industry. 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@shelltown.net 12 East Side Drive #2-18 Concord, NH 03301 http://www.holisticmed.com/aspartame/abuse/methanol.html Scientific Abuse in Methanol/Formaldehyde Research Related to Aspartame Table of Contents Summary of Aspartame Methanol/Formaldehyde Toxicity Hiding the Blood Plasma Methanol Increase From Aspartame Ingestion Methanol and Fruit/Tomatos: Convince the World That a Poison is "Natural" Avoiding the Discussion of Chronic Methanol Toxicity Convince Scientists & Physicians With Irrelevent and Flawed Formate Measurements The "It is Found in the Body, so a Proven Poison Must be Safe" Excuse to Eat Poison Formaldehyde & Formic Acid in Foods: A Final Attempt to Prove a Poison is "Safe" References Summary of Aspartame Methanol/Formaldehyde Toxicity "These are indeed extremely high levels for adducts of formaldehyde, a substance responsible for chronic deleterious effects that has also been considered carcinogenic.... "It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts." (Trocho 1998) "It was a very interesting paper, that demonstrates that formaldehyde formation from aspartame ingestion is very common and does indeed accumulate within the cell, reacting with cellular proteins (mostly enzymes) and DNA (both mitochondrial and nuclear). The fact that it accumulates with each dose, indicates grave consequences among those who consume diet drinks and foodstuffs on a daily basis." (Blaylock 1998) Methanol from aspartame is released in the small intestine when the methyl group of aspartame encounters the enzyme chymotrypsin (Stegink 1984, page 143). A relatively small amount of aspartame (e.g., one can of soda ingested by a child) can significantly increase plasma methanol levels (Davoli 1986a). Clinically, chronic, low-level exposure to methanol has been seen to cause headaches, dizziness, nausea, ear buzzing, GI distiurbances, weakness, vertigo, chills, memory lapses, numbness & shooting pains, behavioral disturbances, neuritis, misty vision, vision tunneling, blurring of vision, conjunctivitis, insomnia, vision loss, depression, heart problems (including disease of the heart muscle), and pancreatic inflammation (Kavet 1990, Monte 1984, Posner 1975). The methanol from aspartame is converted to formaldehyde and then formic acid (DHHS 1993, Liesivuori 1991), although some of the formaldehyde appears to accumulate in the body as discussed above. Chronic formaldehyde exposure at very low doses has been shown to cause immune system and nervous system changes and damage as well as headaches, general poor health, irreversible genetic damage, and a number of other serious health problems (Fujimaki 1992, He 1998, John 1994, Liu 1993, Main 1983, Molhave 1986, National Research Council 1981, Shaham 1996, Srivastava 1992, Vojdani 1992, Wantke 1996). One experiment (Wantke 1996) showed that chronic exposure to formaldehyde caused systemic health problems (i.e., poor health) in children at an air concentration of only 0.043 - 0.070 parts per million! Obviously, chronic exposure to an extremely small amount of formaldehyde is to be avoided. Even if formaldehyde adducts did not build up in the body from aspartame use, the regular exposure to excess levels of formaldehyde would still be a major concern to independent scientists and physicians familiar with the aspartame toxicity issue. In addition to chronic formaldehyde poisoning, the excitotoxic amino acid derived from aspartame will almost certainly worsen the damage caused by the formladehyde. Synergistic effects from aspartame metabolites are rarely, if ever, mentioned by the manufacturer. Aspartame breaks down into a free-form (unbound to protein) excitotoxic amino acid which is quickly absorbed (as long as it is not given in slowly dissolving capsules) and can raise the blood plasma levels of this excitotoxin (Stegink 1987). It is well known that free-form excitotoxins can cause irreversible damage to brain cells (in areas such as the retina, hypothalamus, etc.) in rodents and primates (Olney 1972, Olney 1980, Blaylock 1994, Lipton 1994). In order to remove excess, cell-destroying excitotoxic amino acids from extracellular space, glial cells surround the neuron and supply them with energy (Blaylock 1994, page 39, Lipton 1994). This takes large amounts of ATP. However, formate, a formaldehyde metabolite, is an ATP inhibitor (Liesivuori 1991). Eells (1996b) points out that excitatory amino acid toxicity may be the "mediators of retinal damage secondary to formate induced energy depletion in methanol-intoxication." The synergistic effects from the combination of a chronic formaldehyde exposure from aspartame along with a free-form excitotoxic amino acid is extremely worrisome. It appears that methanol is converted to formate in the eye (Eells 1996a, Garner 1995, Kini 1961). Eells (1996a) showed that chronic, low-level methanol exposure in rats led to formate accumulation in the retina of the eye. More details about chronic Methanol /Formaldehyde poisoning from aspartame can be found on the Internet at http://www.holisticmed.com/aspartame/aspfaq.html. How did the manufacturer convince scientists and physicians that it is "safe" to be exposed regularly to low levels of an exceptionally toxic poison? Answer: Deceptive research and deceptive statements! Hiding the Blood Plasma Methanol Increase From Aspartame Ingestion On February 22, 1984, the acting FDA Commissioner, Mark Novitch stated (Federal Register 1984): "... aspartame showed no detectable levels of methanol in the blood of human subjects following the ingestion of aspartame at 34 mg/kg...." The American Medical Association repeated this statement one year later (AMA 1985). This statement was repeated in American Family Physician in 1989 (Yost 1989). Shaywitz (1994) stated that there was no detectable levels of methanol in the blood after aspartame administration. Puthrasingam (1996) stated that methanol from aspartame is "undetectable in peripheral blood or even in portal blood." All of these statements were very convincing... and very wrong! The statements were based on aspartame industry research which used an outdated plasma methanol measuring test (Baker 1969). The test they used had a limited of methanol detection of 4 mg/l. However, Cook (1991) measured an average baseline (unexposed) methanol level of ~0.6 mg/l. Others (Davoli 1986, d'Alessandro 1994, Osterloh 1996) have measured an average baseline methanol level of close to 1 mg/l. This means that a person's methanol levels would have to rise 350% to 600% before an increase would have been noticed by the industry researchers using this outdated test! An increase of less than 350% to 600% appeared as no increase at all! Probably only a handful of people in the world would have noticed that by using a plasma methanol measuring test with limits of 4 mg/l, they avoided seeing an methanol level increase -- even though there was a large increase. Below are some of the experiments which used the inappropriate methanol measuring technique. Research Aspartame Dosage Lowest Possible Other Claimed to Not Methanol Measurement Methanol Raise Methanol Issues Levels Frey 1976 77 mg/kg Not stated Test conducted after 12-hour fast. All methanol would have been converted to formaldehyde. Stegink 1981 34 mg/kg 4 mg/l Orange juice given despite discussion of high level of methanol in fruit. Stegink 1983 34 mg/kg 4 mg/l ... Leon 1989 75 mg/kg 4 mg/l Test conducted after 12-hour fast. All methanol would have been converted to formaldehyde. Stegink 1989 8 hourly doses 4 mg/kg ... of 10 mg/kg Stegink 1990 8 hourly doses of 10 mg/kg 4 mg/l Fig. 4: Graph of blood methanol concentrations shown with all points well below 4 mg/l -- the lower limit of their methanol test. Hertelendy 1993 15 mg/kg 4 mg/l ... Shaywitz 1993 34 mg/kg 4 mg/l ... Shaywitz 1994 34 mg/kg 4 mg/l ... Note: 10 mg/kg is approximately a one liter bottle of diet soda for a 60 kg adult and 1.5 cans of diet soda for a 30 kg child. Children with aspartame freely-available can ingest between 27 mg/kg - 77 mg/kg (Frey 1976) and adult dieters have been shown to ingest between 8 mg/kg and 36 mg/kg (Porikos 1984). In 1986, Davoli (1986a) published a study which showed that 6 mg/kg to 8.7 mg/kg of aspartame could significantly raise the plasma methanol levels. The methanol levels nearly doubled in some cases. While there were some logical errors in Davoli's conclusion (discussed below), the study proved that by using a reasonable methanol testing method, plasma methanol levels will increase from a relatively low dose of aspartame ingestion. The methanol measuring technique used by Davoli was published in 1985 (Davoli 1986b) and was sensitive to 0.012 mg/l. Other researchers have used sensitive plasma methanol measurement techniques. d'Alessandro (1994) measured plasma methanol levels in humans well below 1 mg/l. Cook (1991) used a methanol test developed in 1981 to measure methanol plasma methanol levels in humans below 0.5 mg/l. What did industry scientists know or should have known? 1.They knew and admited that their methanol testing procedure developed in 1969 was not sensitive enough to detect the large increases of plasma methanol levels when aspartame was given at doses of 34 mg/kg (Stegink 1984b). 2.They must have been aware that Davoli found methanol levels increase significantly when aspartame was given at doses of 6 mg/kg to 8.7 mg/kg. To believe that they were not aware of this, one has to believe that none of the researchers choose to or knew how to conduct a simple Medline database search. 3.They should have known that there were several legitimate plasma methanol measurement techniques developed since 1969. Given that they admited their technique was not appropriate for aspartame doses of less than 34 mg/kg (Stegink 1984b), they should have at least looked to find an appropriate test. 4.Given that Leon (1989) was aware enough to test for formate levels, he must have been aware that all of the methanol from aspartame would have already converted to formaldehyde after a 12-hour fast. I believe that Monsanto/NutraSweet and the aspartame industry are clearly taking advantage of physicians and scientists who lack the time to carefully investigate each number in a study to see if there is deception. While these actions may not amount to "scientific fraud," it does amount to an abuse of the scientific method in my opinion. [end of quote from Gold] Returning to Leon's study of headaches and other symptoms, the subjects were every three weeks (+- 1 week) for 24 weeks, given in a clinic their supply of pills and thorough medical tests, and interviewed about any symptoms: "Subjects were asked at each visit about any unusual symptoms since the previous visit. Elicited symptoms were classified on the basis of the World Health Organization terminology." "The coded adverse experiences fell into 72 terms in 14 World Health Organization (Geneva, Switzerland) organ-systems categories." Of the 108 original volunteers, 101 completed, 51 placebo, and 50 aspartame. "Of the 108 original subjects, 90 (83%) reported 72 different complaints, grouped into 14 World Health Organization organ-system categories, during the course of this 6-month study. There were a total of 193 symptoms in the aspartame group and 130 in the placebo group. Most of the reported symptoms were mild or moderate. There were no visual complaints in either group or ocular findings on physical examination. The most common complaints in each group were headaches, upper repiratory tract symnptoms, and abdominal pain. No consistent pattern of occurrence was noted in these or any other symptoms, nor were there any statistically significant differences between groups in number of subjects experiencing these symptoms or in number of symptoms per subject. There was no statistically significant differerences in the incidence of headaches (the most commonly reported complaint) in the aspartame group compared with the placebo group. Figure 3 shows the frequency of headaches for each group during the course of the study. The pattern displayed here of sporadic fluctuations in incidences of headache in each group was similar to that seen with the other common symptoms." So, no list of symptoms or daily totals of symptoms for each subject-- just recollections every three weeks, "unusual symptoms", "elicited symptoms". Isn't this wonderful? Doesn't that sonorous phrase "World Health Organization" just lull your jaded synapses into sleep-- but wait, just how much was never recorded in the first place, in these interviews of busy students, faculty and staff, every three weeks? After all, one of the most common case complaints for decades is-- impaired memory! How well are people going to remember, weeks later, humiliating episodes of confusion, mind fog, anxiety, depression, anger, insomnia, or report gradually increasing fatigue, subtle retreats from activity, academic dissappointments? And what data there is is not given-- only the reassuring mantra, "no statistically significant differences", in unreassuring contrast to the stark, dramatic, and chaotic results of the independent studies, which used lower doses for far shorter periods. Some subjects must have tossed their capsules in the can, not their mouths, and collected their pay-- how much, by the way? Others must have taken up daily doses of aspirin and the like. The redoubtable Table 3 shows a decrease from about 8 aspartame subjects with headaches in the first 3-week period to about 4 in each of the last four three-week periods: 8, 4, 7, 7, 5, 5, 4, 4 -- this is in absolute contradiction with the three independent studies. The placebo subjects actually reported a rise in people with headaches: 4, 2, 6, 7, 1, 5, 6, 11 . The senior authors, Leon and Hunninghake, are invited to render a public service to science by releasing their raw data on symptoms. ************************************************************* Rich Murray Room For All rmforall@att.net 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@aol.com sunsentpress@aol.com 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 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 (male) "Trok-ho" Tel.: (93)4021521, Fax: (93)4021559 alemany@porthos.bio.ub.es bioq@sun.bq.ub.es rafecas@porthos.bio.ub.es remesar@porthos.bio.ub.es Sra. Carme Trocho Tel.: (93)4021544, Fax: (93)4021559 **************************************************************