From: Rich Murray [rmforall@att.net] Sent: Sunday, August 04, 2002 5:54 PM To: fdadockets@oc.fda.gov Subject: RTM: FDA: (Section B) Samuels: Strong: Roberts: Gold: flaws in double-blind studies re aspartame and MSG toxicity 8.1.2 rmforall RTM: FDA: (Section B) Samuels: Strong: Roberts: Gold: flaws in double-blind studies re aspartame and MSG toxicity 8.1.2 rmforall http://groups.yahoo.com/group/aspartameNM/message/858 Double-blind studies, labelled with sonorous adjectives, "experimental", "laboratory", "clinical", "controlled", "randomized", have great scientific and commercial prestige as the gold standard for "stastistically significant" truth. A single such study can be used to cast doubt, disbelief, and dismissal on the "anecdotal evidence" of numerous citizen and doctor complaints, on careful, detailed clinical reports in throroughly professional, peer-reviewed journals, and on conclusions that might otherwise arise logically from basic biochemical facts. Actually, double-blind studies are extremely trickly, complex, subtle, dicey, susceptible to a multitude of mistakes, and amazingly easy to manipulate toward desired goals and preordained conclusions. And they are expensive-- easily a hundred thousand dollars for a scientists and a few assistants to run a few dozen human subjects for a month or two. But, what's a hundred grand, or a million, to a global corporation that is motivated to legitmize the effectiveness and safety of a product that can garner a billion dollars of sales in its first year? Corporate funding can keep a pet scientific teams in lolly for decades, create a journals to publicize results in, set up yearly international conferences, and place expensive ads to influence the editors, publishers, and readers of independent journals. Favorable results are trumpeted over and over for years to doctors, government agencies, and the people: "Aspartame is the most tested food additive in history. No careful, scientific findings support any anecdotal claims of aspartame toxicity." http://www.truthinlabeling.org/ Truth in Labeling Campaign [MSG] Adrienne Samuels, PhD P.O. Box 2532 Darien, Illinois 60561 858-481-9333 adandjack@aol.com "The Toxicity/Safety of Processed Free Glutamic Acid (MSG): A Study in Suppression of Information" Accountability in Research (1999) Vol 6, pp. 259-310 http://www.truthinlabeling.org/l-manuscript.html [Extracts] http://www.truthinlabeling.org/L-ref.htm References The Double-Blind Studies In the 1980s, in the face of overwhelming evidence that monosodium glutamate kills brain cells in laboratory animals (Olney and Price, 1978, 1980), industry researchers changed their strategy. They began to claim that animal studies were not relevant to humans. They initiated a series of double-blind human studies that, they would claim, "proved" that monosodium glutamate was safe. A number of industry-sponsored double-blind studies followed the epidemiologic study. Detailed analysis of those double-blind studies revealed that subjects, materials used, and protocols for administering test and placebo material, minimized the chance that subjects would react to the MSG test material; and that if subjects did react to the MSG test material, they would also react to the placebo. Industry researchers: 1. Use variables and methods known to minimize or be irrelevant to identification of the toxic effects of glutamic acid; then conclude that glutamic acid never produces adverse effects. Studies have focused on the relationship between "objective" parameters such as blood pressure and body temperature and ingestion of MSG. Unless MSG sensitive people are studied, one can not legitimately draw conclusions about the relationship of the variables being studied (no matter how objective they are) to people who are sensitive to MSG. Often, these studies are used to allegedly "prove" that people who are not sensitive to MSG are not sensitive to MSG. 2. Limit the recorded adverse effects to a few generally mild and transitory reactions occurring simultaneously, such as those first reported in 1968 by Kwok and dubbed "Chinese- restaurant syndrome" (CRS): "...numbness at the back of the neck, gradually radiating to both arms and the back, general weakness and palpitation." Industry researchers do not consider migraine headache, asthma, tachycardia, arrhythmia, depression, anxiety attacks or other obviously debilitating and/or life-threatening reactions reported since 1968. 3. Make no attempt during a study to prevent subjects from ingesting food to which they might be allergic or sensitive. 4. Record reactions as reactions to monosodium glutamate or placebo material only if they occur 2 hours or less following ingestion of test or placebo material, even though many symptoms are commonly expressed much later, and reactions may persist for much longer periods. 5. Fail to report all data. 6. Draw conclusions that do not follow from the results of the study. The IGTC researchers have concluded, for example, that because approximately one third of their subjects reacted adversely to placebos containing MSG and/or aspartame, they have "proved" that reactions to MSG-containing test material are not reactions to MSG. 7. Use test material that will minimize the effect of any stated amount of glutamic acid test material in producing adverse reactions. One gram monosodium glutamate encased in capsules, and therefore guaranteeing slow release, will cause less effect than 1g monosodium glutamate sprinkled on food; and 1g monosodium glutamate modified with sucrose will cause less effect than otherwise because sucrose is known to slow monosodium glutamate uptake (Stegink, 1986). 8. Continue subjects on medications that might block the effects of MSG. 9. Using placebos to which MSG-sensitive people would react (placebos containing MSG, aspartame, carageenan or enzymes, for example), test potential subjects for sensitivity to those placebos, and eliminate any subjects who react to placebos. Researchers can be fairly certain that those who do not react to their reactive placebos will not react to monosodium glutamate test material. 10. Advertise for, and presumably use, "well subjects" – people who had never experienced any of the symptoms with which reactions to MSG are associated. (If 50 per cent of the population were sensitive to MSG, but research design precluded inclusion of that 50 per cent who were sensitive, a study claiming to assess the number of people sensitive to MSG would be invalid.) 11. Refer to studies as "randomized double-blind crossover design studies," which gives the casual reader the impression that subjects were drawn randomly from the general population. In fact, subjects are often carefully selected people who tell researchers that they have never experienced any of the adverse reactions associated with monosodium glutamate, and, under those conditions, are paid to participate in the studies. Other subjects are people, often students, paid for participating in industry-sponsored studies only if they say that they are sensitive to monosodium glutamate. In either case, the only thing in those studies that is "random" is whether subjects get their monosodium glutamate test trial first and their placebo second, or vice versa. Subjects recruited in 1993 for as yet unpublished IGTC-sponsored studies begun in 1992 by Harvard Medical School, Northwestern University Medical School, and UCLA Medical School, were paid hundreds of dollars each-- only if the applying subjects (many of them students) claimed that they were sensitive to monosodium glutamate. One of my children, a Northwestern student at the time, saw the study advertised, found out the details of participation, applied for the study, and was rejected when she told the researchers that she was not very sensitive to MSG. 12. Use placebos virtually guaranteed to produce as many reactions as might be produced following ingestion of the monosodium glutamate test material. Using toxic material in both test material and placebo, researchers argue that the reactions to MSG-containing test material are not reactions to MSG because subjects also react to placebos, which are assumed to be inert. However, the use of toxic material in placebos, particularly when it is identical or similar to the MSG in the test material, makes it virtually inevitable that there will be approximately as many reactions to placebos as there are reactions to MSG test material. Sometimes glutamate-industry researchers use MSG in placebos, but use sources of MSG different than the ingredient called monosodium glutamate. Gelatin, which always contains free glutamic acid, has been a favorite. Beginning in 1978, before aspartame was approved by the FDA for use in food, glutamate-industry researchers used aspartame in placebos (Ebert, 1991b). Over and above the fact that use of aspartame in placebos is grossly inappropriate, the fact that aspartame-containing products are supposed to carry a warning on their labels did not deter industry from using the substance, or the FDA from allowing its use. Aspartame contains phenylalanine (which adversely affects one in 15,000 Americans); aspartic acid (an excitatory amino acid); and a methyl esther. Aspartic acid and glutamic acid load on the same receptors in the brain, cause the same brain damage and neuroendocrine disorders in experimental animals, and, with the exception of blindness related to aspartame ingestion, cause virtually the same adverse reactions in humans. There are over 7,000 unsolicited reports of adverse reactions to aspartame filed with the FDA. It should surprise no one, therefore, that glutamate industry researchers find as many reactions following ingestion of an aspartame-containing placebo as they find following ingestion of monosodium glutamate test material. Placebo reactions have also been noted in industry-sponsored animal studies. It was noted by Nemeroff (1981) that Abraham, Doughtery, Goldberg, and Coulston (1971) and Abraham, Swart, Goldberg, and Coulston (1975) found in both control and glutamic acid treated monkeys a "very small proportion of necrotic or damaged neuronal cells and oligodendrocytes... in the arcuate nuclear region of the hypothalamus." This might happen if the placebo, as well as the test material, contained small amounts of an excitotoxin identical or similar to glutamic acid. On February 4, 1991 at the FASEB open hearing on the safety of amino acids in dietary supplements, J. Samuels raised the question of the propriety of placebo material used by the glutamate industry. Ebert rebutted, leading to a request from Sue Anne Anderson, R.D., Ph.D., Senior Staff Scientist with the Life Sciences Research Office at FASEB for information about the vehicle for administration of monosodium glutamate in IGTC-sponsored double blind studies. In a March 22, 1991 letter to Anderson, IGTC chairman Ebert responded that "since the completion of the work described in [1978], the sample has been modified to replace the sucrose with the low calorie sweetener Aspartame in both the placebo and sample with MSG." Still, no one at the FDA raised any question about the propriety of the research being submitted to the FDA by the IGTC as evidence that MSG is safe. [Ebert, A.G. (1991b). Letter to Sue Ann Anderson, R.D., Ph.D., Senior Staff Scientist, FASEB. March 22, 1991.] In 1993, J. Samuels came across the March 22, 1991 letter to Anderson in the files of the FDA; and brought the information to the attention of both FASEB and the FDA. Still, no one at the FDA raised any question about the propriety of the research being submitted to the FDA by the IGTC as evidence that MSG is safe. Not long afterward, IGTC chairman Ebert was named by FDA Commissioner David A. Kessler, M.D., to the FDA Food Advisory Committee. The IGTC has amassed a number of double-blind studies concluding--but not demonstrating--that MSG is safe. The fact that these studies are often done at generally respected universities or medical schools, all of which required that the research be approved by medical research review committees, has public relations value. Subsequently, studies may be published in peer reviewed journals-- accepted by editors who, themselves, may have ties to the food and/or drug industries. Given the methodological flaws inherent in their work, and their unwillingness to change their protocols after flaws were pointed out to them, it would appear that IGTC researchers move from a predetermined conclusion (that their product is "safe") to design and implementation of research guaranteed to bring the reader back to that predetermined conclusion. ********************************************************** These critiques certainly apply to scores of industry and industry funded research on aspartame, often by the same firms and researchers. http://groups.yahoo.com/group/aspartameNM/message/844 RTM: layman lament: NutraSweet: aspartame & neotame toxicity 7.12.2 rmforall [Extract] Suppose aspartame causes 1 out of a 100 ordinary folk to have headaches. Suppose you spend a hundred grand to compare 100 users vs 100 matched nonusers for a month. Well, the group of 100 users is fairly likely to have 0, 1, or 2 vulnerable persons, who would react by having maybe twice as many headaches. So, there is a good chance that the expnsive experiment wouldn't pick up any excess headaches at all. Yet, for 200 million users in the USA, 1 out of a 100 would, in this example, be 2 million people with twice as many headaches. That's the problem with big expensive, double-blind laboratory tests. If both the users and nonusers already have a fairly high and erratic incidence of headaches, then it will be far more problematic to prove the effects of a single factor like aspartame. We have to know whether the control group was given a "placebo" that also caused headaches. For instance, was neotame played against aspartame or MSG? I kid you not. Then, suppose the groups compared are paid, young, healthy, educated, privileged college students, who take aspirin freely and don't mention it. Then, as the Spiers (1989) study found, the group that had the most aspartame had fewer headaches. Also, whether you are studying people or rats, just by losing a single subject, or fudging the data on a single subject, in a group of 100, you can easily eliminate the possibility of detecting a 1 out of 100 incidence. So, easy, really, with all that money and approval from the corporate guys, to just develop the nice, neat evidence they need to reduce the ravages of sugar bingeing. Who's to know? Several studies can be done with different teams, and the unwanted ones simple filed away quietly in a drawer. After all, they belong to the corporation that buys them. Right? And, even if the research is absolutely impecable, what can it say about all the different vulnerable groups, unluckily not young jocks and monkish nerds? Now, since 1995, the Net allows the user group to be society as a whole. There's a support group now for every problem and illness. GFCFKids@yahoogroups.com has as of today 2,558 members, with 98,666 posts in their archive since 12.15.98, discussing the problems of kids who are hypersensitive to gluten in wheat and casein in milk. It's free. So, even rare conditions can lead to highly organized, active, outspoken, influencial groups, independent of control by corporations, governments, and medicos. Aspartame@yahoogroups.com has 431 members, and 13,709 posts since 12.31.99, while my group aspartameNM@yahoogroups.com has 81 members and 844 posts since 10.22.99. ********************************************************* 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 "Survey of aspartame studies: correlation of outcome and funding sources," 1998, unpublished: This study is available at http://www.dorway.com/peerrev.html Al Raetz has justly criticized bias in both sides of the debate: www.aspartametruth.freeservers.com/personal.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. ********************************************************* http://groups.yahoo.com/group/aspartameNM/message/285 Strong FC Why do some dietary migraine patients claim they get headaches from placebos? Clin Exp Allergy 2000 May; 30(5): 739-43. Departamento de Ciencia de Alimentos Faculdade de Engenharia de Alimentos Universidade Estadual de Campinas, SP, Brasil http://www.unicamp.br/unicamp/universidade/universidade.html and Department of Chemistry, Bucknell University www.bucknell.edu 570-577-2000 Lewisburg, PA, USA. Strong Frederick C fstrong@bucknell.edu c/o C H Clapp Chemistry Dept, Graduate/Special, guest BACKGROUND: In six double-blind studies involving 182 tests of dietary migraine patients sensitive to tyramine and beta-phenylethylamine, 18% reported headaches from placebos which were all concealed in gelatin capsules. OBJECTIVE: The purpose of this research was to test a hypothesis: gelatin is partially hydrolysed animal protein; (partially) hydrolysed vegetable protein (PHVP) is known to cause migraine; perhaps the gelatin caused some of the headaches. METHOD: The author tested this hypothesis on himself because he suffers from dietary migraine. He proved this in a double-blind test with tyramine hydrochloride (TYH). The amount required for the test was so small (1 mg) that it was tasteless and capsules were unnecessary. The author then undertook tests with a capsule, PHVP, monosodium glutamate (MSG) aspartame (a dipeptide) and TYH, adjusting quantities to give a moderate headache. Samples were mixed with foods to simulate normal eating: the capsule with potato chips, aspartame with orange juice and the rest with cottage cheese or ricotta cheese. Times were measured from ingestion (1) to start of the headache and (2) to maximum headache intensity. Each experiment was repeated three times. The headaches were relieved with caffeine. RESULTS: Of eight double-blind test samples, the author identified correctly the two placebos and five of the six samples containing tyramine. Quantities giving moderate headaches were: 1 gelatin capsule, 400 mg MSG, 118 mg PHVP, 4.0 mg aspartame and 1.0 mg TYH. Typical times for the three repetitions of the two time periods were 8, 9 and 11 and 17, 19 and 22 min. CONCLUSIONS: Capsules may give headaches to dietary migraine patients that are similar to those from foods. This would explain some of the headaches of patients from placebos. The double-blind test and the repeatability of the time measurements demonstrated the validity of the experiments. PMID: 10792367, UI: 20252980 ********************************************************** [Comments by Rich Murray are in square brackets.] Roberts HJ Aspartame and headache. Neurology 1995 Aug; 45(8): 1631; discussion 1632-3. Comment on: Neurology. 1994 Oct; 44(10): 1787-93. Publication Types: Comment Letter PMID: 7644072 To the Editor: The report by Van Den Eeden et al (1) validates my repeated encounter of headache specifically atttributable to the ingestion of products containing aspartame (NutraSweet.). (2-7) About 47% of persons in my series of more than 650 aspartame reactors reported recurrent or de novo headaches, even when previously controlled by medication. Moreover, one-half of the patients with aspartame-induced seizures (more than 130) experienced increasingly severe headache before their first convulsion. (5-7) [Three independently funded double-blind studies that show that aspartame causes headache are contrasted with three industry funded studies to the contrary, along with a critique of the vulnerability of these studies to faulty design and execution. The validity of Roberts' main research strategy of assessing hundreds of clinical cases and consumer complaints is butressed by recent clinical reports of headache caused by 3.75 mg aspartame in migraine medication and by the 6-8 mg aspartame in chewing gum, as well as the report in 2001 of four cases of intractable fibromyalgia, finally resolved by avoiding all aspartame and MSG. The pattern of pathology in the total of 9 cases in these 3 reports is the same as the over thousand case reports summarized by Roberts in letters, articles, and texts, replicating closely his clinical methods, data, and conclusions: http://www.dorway.com/tldaddic.html 5-page review Roberts HJ Aspartame (NutraSweet) addiction. Townsend Letter 2000 Jan; HJRobertsMD@aol.com http://www.sunsentpress.com/ sunsentpress@aol.com Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416 800-814-9800 561-588-7628 561-547-8008 fax http://groups.yahoo.com/group/aspartameNM/message/669 1038-page medical text "Aspartame Disease: An Ignored Epidemic" published May 30 2001 $ 85.00 postpaid data from 1200 cases available at http://www.amazon.com over 600 references from standard medical research http://www.aspartameispoison.com/contents.html 34 chapters http://groups.yahoo.com/group/aspartameNM/message/790 RTM: Moseley: review Roberts "Aspartame Disease: An Ignored Epidemic" 2.7.2 rmforall http://groups.yahoo.com/group/aspartameNM/message/622 Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon: aspartame toxicity 6.4.1 rmforall http://groups.yahoo.com/group/aspartameNM/message/623 Rich Murray: Simmons: Gold: Schiffman: Spiers: aspartame toxicity 6.4.1 rmforall http://groups.yahoo.com/group/aspartameNM/message/854 RTM: Newman & Lipton: 3.75 mg aspartame in Merck Maxalt-MLT worsens migraine Oct 2001 7.28.2 rmforall http://groups.yahoo.com/group/aspartameNM/message/855 RTM: Blumenthal & Vance: aspartame chewing gum headaches Nov 1997 7.28.2 rmforall http://groups.yahoo.com/group/aspartameNM/message/652 Smith JD, Terpening CM, Schmidt SO, Gums JG Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins. terpening@fpmg.health.ufl.edu cterpeni@ufl.edu Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA. gums@fpmg.health.ufl.edu siggy@shands.ufl.edu http://groups.yahoo.com/group/aspartameNM/message/782 RTM: Smith, Terpening, Schmidt, Gums: full text: aspartame, MSG, fibromyalgia 1.17.2 rmforall ] This report undoubtedly underestimates the frequency of the problem. It also raises several issues pertaining to the methodology used by these and previous investigators. They warrant comment because I believe these investigations have misled researchers and readers both within this realm and in the realm of other neuropsychiatric reactions to aspartame products. The latter include convulsions, depression, hyperactivity and cognitive changes in children, confusion, dizziness, visual problems, tremors, and insomnia. (2-7) For example, I disagree with the assurance offered by Shaywitz and Novotny in your journal (8) that "aspartame consumption will not provoke or exacerbate seizures." I have challenged the administration of aspartame as capsules or in freshly prepared cool solutions rather than in "real world" products-- viz, soft drinks and other products sold in markets. The latter undergo changes upon exposure to high temperature and with prolonged storage (ie, more than 2 months). Similar considerations apply to the addition of aspartame tabletop sweeteners to hot beverages. The ensuing stereoisomers and multiple metabolites of aspartame may be as neurotoxic as the chemical itself. Furthermore, capsules of aspartame do not elevate phenylalanine, aspartic acid, and methanol concentrations to levels comparable to those following ingestion of aspartame in liquid form. [ http://groups.yahoo.com/group/aspartameNM/message/830 RTM: Tholen: Diet Coke has 5 ppm formaldehyde from aspartame 5.29.2 rmforall For a science project, Randy Tholen, age 11, had six cans of Diet Coke analyzed on 3.7.2: Contact/Phone: Bill Katz 952-942-1774 bkatz@brauncorp.com Braun Intertec Corporation http://www.brauncorp.com/ (800) 279-6100 (952) 941-5600 fax (952) 833-4701 6875 Washington Ave. S. Minneapolis, MN 55439 For 6 cans of diet soda, this is 5 times the daily limit of 1 PPM for formaldehyde in drinking water, set by the EPA. ] I also must voice reservations about both the aspartame and the placebo used. In view of the need to avoid criticism of double-blind studies along these lines, I recommend that the aspartame be obtained from independent chemical suppliers and analyzed by corporate-neutral persons. [ It is prudent to doubt all independently unconfirmed research, however voluminous, by industry or industry funded researchers, especially when there is a dismal historical record of research integrity: http://groups.yahoo.com/group/aspartameNM/message/857 RTM: www.dorway.com: original documents and long reviews of flaws in aspartame toxicity research 7.31.2 rmforall ] A case in point is the experience of Walton et al. (9) They sought to ascertain whether persons with a history of depression are more vulnerable to the adverse effects of aspartame. Aspartame capsules and placebos of identical appearance were administrated in a double-blind challenge involving patients with a history of unipolar depression and a control group. Inasmuch as the NutraSweet Company refused to sell these investigators aspartame, they purchased analytically certified USP-grade aspartame from a distributor. The frequency and severity of psychiatric, neurologic, eye and other complications in the depression group forced the institutional review borad to terminate the study prematurely. [The implication is that the independently provided aspartame is far more potent than that supplied by NutraSweet to researchers. Suspiciously, Schiffman et al, 1987, found that 40 aspartame sensitive students had fewer headaches (35% headache incidence rate) from a single dose of aspartame than with a placebo (45% incidence rate), a non-significant result, clearly at odds with the many case reports and three independently funded double-blind experiments.] The composition of placebos also must be clarified to exclude the presence of excitotoxins. The need for such exclusion recently came to light when the placebo given persons with alleged reactions to monosodium glutamate (MSG) was found to contain aspartame! This probably accounted for the striking frequency of reactions in the "control" group. I regret having to raise these matters. They must be clarified, however, because more than half the population now consumes enormous amounts of a chemical that I regard as an imminent public health neurotoxic hazard. H.J. Roberts, MD West Palm Beach, FL *********************************************************** http://www.nutrasweet.com/search/index.asp Consumer Center Answers on Aspartame Q5. Does aspartame cause headaches? A5. No, aspartame does not cause headaches. Headaches are one of the most common human ailments. Many factors can cause headaches, ranging from stress and sleep disturbances to physical illnesses. It is potentially dangerous to assume that a headache is related to aspartame, when the cause may be a serious psychological or physical condition. If you are concerned about headaches, speak to your physician. A carefully controlled clinical study published in the New England Journal of Medicine (1) supports the fact that aspartame does not cause headaches or migraines. The results showed that 35 percent of the subjects had headaches after taking aspartame, compared with 45 percent who had headaches after taking the placebo, confirming that aspartame does not trigger headaches. (1) Schiffman S et al, "Aspartame and susceptibility to headache," New England Journal of Medicine, Vol. 317, 1987, pp. 1181-1185. ********************************************************** http://groups.yahoo.com/group/aspartameNM/message/622 Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon: aspartame toxicity 6.4.1 rmforall http://groups.yahoo.com/group/aspartameNM/message/623 Rich Murray: Simmons: Gold: Schiffman: Spiers: aspartame toxicity 6.4.1 rmforall Schiffman SS, Buckley CE 3d, Sampson HA, Massey EW, Baraniuk JN, Follett JV, Warwick ZS Aspartame and susceptibility to headache. N Engl J Med 1987 Nov 5; 317(19): 1181-5. Department of Psychiatry, Duke University, Durham, N.C. 27710. Dr. Susan S. Schiffman Dept. of Psychiatry Duke University www.duke edu sss@acpub.duke.edu 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@tiac.net 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] ********************************************************* Rich Murray, MA Room For All rmforall@att.net 1943 Otowi Road, Santa Fe NM USA 87505 505-986-9103 http://groups.yahoo.com/group/aspartameNM/messages for 862 posts http://groups.yahoo.com/group/aspartameNM/message/861 brief summary http://groups.yahoo.com/group/aspartameNM/message/862 long summary http://groups.yahoo.com/group/aspartameNM/message/860 RTM: FDA: objections to neotame approval (Section A) 8.4.2 rmforall http://groups.yahoo.com/group/aspartameNM/message/829 RTM: Roberts: Pseudotumor Cerebri Due to Aspartame Disease: Townsend Letter 5.25.2 rmforall Townsend Letter for Doctors & Patients June, 2002 http://www.tldp.com/ tldp@olympus.net 360-385-6021 Fax 360-385-0699 H. J. Roberts, M.D., FACP. Pseudotumor Cerebri due to aspartame disease. Townsend Letter for Doctors & Patients June, 2002; #227: 66-68. Abstract: Objectives. Clinical insights concerning a remediable cause of pseudotumor cerebri (benign intracranial hypertension) due to aspartame disease. Materials and Methods. Observations of six women with pseudotumor cerebri who consumed considerable aspartame products, especially "diet" sodas. Results. The ocular and other manifestations of aspartame disease disappeared or dramatically improved in all subjects after avoiding aspartame products, even obviating surgery. Conclusions. Aspartame disease should be considered in patients presenting with pseudotumor cerebri, especially weight-conscious young women. The associated clinical features and underlying mechanisms are reviewed with emphasis on chronic methanol toxicity. **********************************************************