From: Rich Murray [rmforall@att.net] Sent: Monday, August 05, 2002 1:58 AM To: fdadockets@oc.fda.gov Subject: RTM: FDA: (Section C) Newman & Lipton: 3.75 mg aspartame in Merck Maxalt-MLT worsens migraine Oct 2001 7.28.2 rmforall RTM: FDA: (Section C) 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/854 [Comments by Rich Murray are in square brackets.] Headache 2001 Oct; 41(9): 899-901. Migraine MLT-Down: An Unusual Presentation of Migraine in Patients With Aspartame-Triggered Headaches. Newman LC, Lipton RB. Headache Institute, St. Lukes-Roosevelt Hospital Center, New York NY Department of Neurology Albert Einstein College of Medicine, Bronx, NY Innovative Medical Research Aspartame, an artificial sweetener added to many foods and beverages, may trigger headaches in susceptible individuals. We report two patients with aspartame-triggered attacks in whom the use of an aspartame-containing acute medication (Maxalt-MLT) worsened an ongoing attack of migraine. PMID: 11703479 [Extracts] Two patients successfully treated wtih triptans developed headache exacerbation following treament with an aspartame-containing formulation of rezatriptan (Maxalt-MLT). (1) [Contains 3.75 mg aspartame.]... Anecdotal evidence and observational studies suggest that aspartame is a potential migraine trigger. (3, 4) Although two double-blinded studies support these results, a third study did not. (5-7) [The third study was the only one paid for by NutraSweet Co: Schiffman, 1987. For a detailed critique of these studies: 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 ] Patient 1.--A 14-year-old boy had a 2-year history of migraine. Headaches initially ocurred on a daily basis, but for the past year, occurred once or twice monthly. The pain was throbbing, moderate to severe in intensity, and associated with photophobia and phonophobia. A visual aura, consisting of scintillating scotomata, preceded most attacks. Using an elimination diet, aspartame-containing foods and drinks were identified as consistent triggers. Aspartame usually induced a typical attack within hours of ingestion. Treatment with dihydroergotamin injections, and nasal spray and oral preparations of sumatriptan, zolmitriptan, and rizatriptan would abort an acute migraine attack within 45 minutes. At the patient's request, he was given samples of the rizatriptan oral wafers, so he could more easily treat his headaches while in school. Although his headaches had been rapidly aborted with oral rizatriptan on at least 20 prior occasions, following administration of the wafer, his headache worsened and persisted for approximately 6 hours. A rizatriptan tablet relieved his next headache within 45 minutes. Patient 2.--A 36-year-old woman had a 30-year history of migraine without aura. Headaches occurred approximately 2 to 4 times monthly and were associated wtih nausea, vomiting, photophobia, phonophobia, and osmophobia. Using an elimination diet, monosodium glutamate, nitrites, and aspartame-containing foods were identified as consistent triggers, usually within 2 hours following ingestion. Treatment with oral rizatriptan, on at least 15 occasions, afforded consistent relief within 45 minutes. Following administration of the oral disintegrating wafer formulation of rizatriptan, the patient reported a steadily worsening migraine that lasted 6 hours. Treatment of her next attack with the tablet formulation of rizatriptan aborted the migraine within 45 minutes.... Since both the table and wafer contain 10 mg of rizatriptan and have similar kinetic profiles, these results were initially difficult to understand... the 10-mg wafer contains 3.75 mg of aspartame; for comparison, a packet of aspartame (as a nonsugar sweetener) contains 37 mg of aspartame. (1) A dose [ ~ 20 mg aspartame] equivalent in sweetening to a teaspoon of sugar contains roughly five times as much aspartame as a rizatriptan wafer... In 1981, the United States Centers for Disease Control reviewed consumer complaints related to the use of aspartame. (2) Neurologic or behavioral symptoms were reported in 67%: the most frequently mentioned single complaint, headache, was reported in 22%... Survey data of a headache-prone population suggests that aspartame is a common headache trigger. In a sample of 171 consecutive patients with headache, regarding the role of dietary factors and headache, aspartame was reported as a headache precipitant by 8.2%, significantly more often than carbohydrates, the food used as a negative control. (3). Johns described a patient who developed a vascular headaches and gastrointestinal symptoms following the ingestion of aspartame-containing soft drinks. (4) Similar symptoms occurred when the patient was rechallenged with solutions of aspartame but not with saccharin. Blumenthal and Vance described 3 patients in whom aspartame-containing chewing gum induced typical migraine attacks. (8) [6-8 mg aspartame per stick] ... We have previously discussed some of the limitations of the Schiffman study. (9)... Both patients had previously reported that aspartame was a potent and consistent migraine trigger... The doses of aspartame reported to trigger a migraine attack de novo are generally higher than those reported here. Unfortunately, neither patient would agree to a rechallenge with the wafer formulation. If this phenomenon exists, it is likely to be rare. Nonetheless, clinicians should be aware that rizatriptan wafers contain aspartame. This preparation should probably be avoided in patients with known sensitivity to aspartame... REFERENCES 1. Physicians' Desk Reference. 54th ed. Medical Economics Co; Montvale, N.J.: 2000: 1956-1960. 2. Anonymous. Evaluation of cusumer complaints related to aspartame use. MMWR Morb Mortal Wkly Rep. 1984; 33: 605-607. 3. Lipton, RB, Newman LC, Cohen JS, Solomon S. Aspartame as a dietary trigger of headache. Headache. 1989; 29: 90-92. 4. Johns DR. Migraine provoked by aspartame (letter). N Engl J Med. 1986; 315: 456 5. Schiffman SS, Buckley CE III, Sampson JA, et al. Aspartame and susceptibility to headache. N Engl J Med. 1987; 317: 1181-1185. 6. Koehler SM, Glaros A. The effect of asparame on migraine headache. Headache. 1988; 28: 10-14. 7. Van den Eeden SK, Koepsell TD, Longstreth WT Jr, van Belle G, Daling JR, McKnight B. Aspartame ingestion and headaches: a randomized crossover trial. Neurology. 1994; 44: 1787-1793. 8. Blumenthal HJ, Vance DA. Chewing gum headaches. Headache. 1997; 37: 665-666. 9. Lipton RB, Newman LC, Solomon S. Asparame and headache (letter). N Engl J Med. 1988; 318: 1200-1202. ********************************************************* http://www.docnet.org/physicians/phys_bios.asp?phys_id=574 Lawrence C. Newman, MD 212-523-5869 newmanache@aol.com St. Luke's-Roosevelt Hospital Center Headache Institute 1000 10th Avenue, Room 1C-10 New York, NY 10019 Prof. Neurology, Epidemiology & Social Medicine Albert Einstein College of Medicine at Yeshiva University http://msl.montefiore.org/newmsl/default.htm Dr. Richard B. Lipton, Department of Neurology Montefiore Medical Center 111 East 210th Street, Bronx, NY 10467, USA. FAX 203-321-1044 Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx, NY 10461 718-430-3886 fax 3870 MMC - Headache Unit 111 E. 210th Street Bronx , NY 10467 718-920-4638 http://www.imrinc.com/ webmaster@imrinc.com Innovative Medical Research, Inc. Alberto R. Yataco, M.D. Richard B. Lipton, M.D., Chief Science Officer RLipton@IMRInc.com 1001 Cromwell Bridge Rd., Suite 302 Towson, MD 21286 USA 410-825-0500 Fax: 410-339-7086 http://www.centerwatch.com/professional/pro111.html President American Headache Society Richard B. Lipton, MD Professor of Neurology, Epidemiology and Social Medicine Albert Einstein College of Medicine Innovative Medical Research, Inc. 1200 High Ridge Road Stamford, CT 06905 203-321-1050 fax 1044 rlipton@imrinc.com Fall & Winter Symposium Co-Chairs Lawrence C. Newman, MD * The Headache Institute 1000 Tenth Avenue New York, NY 10019 212-523-5869 fax5902 (fax) newmanache@aol.com American Headache Society http://www.ahsnet.org/ 19 Mantua Road Mt. Royal, NJ 08061 856.423.0043 fax 0082 ahshq@talley.com Headache: The Journal of Head and Face Pain http://ahsnet.org/journal/ Merck and Co., Inc. http://www.merck.co Peter S. Kim, PhD Exec. VP, R&D age 43 kimadmin@wi.mit.edu 617-258-5184 fax 5737 MRL 770 Sunnytown Pike West Point PA 19486 Edward M. Scolnick, MD Exec. VP, Sci & Tech, Pres. of MRL age 61 MRL P.O.Box 2000 Rayway, NJ 07065-0900 732-594-3761 William A. Peck, MD Exec V. Chancellor for medical affairs WUSOM peckw@msnotes.wustl.edu 314-362-6827 Bennett M. Shapiro, MD, Exec. VP, Merck Worldwide Basic Research 732-594-3761 Raymond V. Gilmartin, CM, Pres., CEO, Merck & Co., Inc. One Merck Drive P.O.Box 100 Whitehouse Station, NJ 08889-0100 fax 908-735-1253 http://www.neuro.wustl.edu/people/choi.html Home Page Dennis Wonkyu Choi, MD, PhD age 48 Hired Nov 13 2001 by Merck Research Labortories as Executive VP, Neurosciences Dennis Choi is the Andrew B. and Gretchen P. Jones Professor and Head of the Department of Neurology at Washington University in St. Louis, as well as the Neurologist-in-Chief at Barnes-Jewish Hospital. 866-867-3627 info BIOGRAPHICAL SKETCH Dr. Choi was born in Ann Arbor, Michigan, and grew up in Watertown, Massachusetts. He graduated from Harvard College in 1974, and in 1978 received the MD and PhD degrees (the latter in Pharmacology) from Harvard University and the Harvard-MIT Program in Health Sciences and Technology. After completing residency and fellowship training in neurology at Harvard in 1983, he joined the faculty at Stanford University, and then 1991 came to Washington University Medical School to chair the Neurology Department. At Washington University, he also directs the Center for the Study of Nervous System Injury and the McDonnell Center for Cellular and Molecular Neurobiology. He is the chairman of the US / Canada Regional Committee of the International Brain Research Organization, a past President of the Society for Neuroscience, and a past Vice-President of the American Neurological Association. He is a member of the Institute of Medicine, and has served on the Councils of the National Institute of Neurological Disorders and Stroke, the Society for Neuroscience, the Winter Conference for Brain Research, the International Society for Cerebral Blood Flow and Metabolism, and the Neurotrauma Society. He is a member of the editorial boards of more than a dozen journals including Science, and is a founding co-editor of Neurobiology of Disease, a journal positioned at the interface of basic and clinical neuroscience. He is presently an Associate of the Neurosciences Institute in San Diego and a member of the Dana Alliance for Brain Research. Current or past service on scientific advisory boards has included the Christopher Reeve Paralysis Foundation, the Grass Foundation, the Hereditary Disease Foundation, the Queen's Neuroscience Institute in Honolulu, the Max-Planck Institute in Heidelberg, the Korea Institute for Advanced Study (KIAS) in Seoul, and the US Food and Drug Agency, as well as several university-based research consortia in the US and Europe, and several companies. RESEARCH SUMMARY The work of my laboratory is directed toward elucidating the cellular mechanisms underlying CNS injury in neurological disease states, and developing therapeutic countermeasures. A long-standing interest has been the "excitotoxic" neuronal injury produced by excess exposure to glutamate and other endogenous excitatory amino acids. Excitotoxicity likely contributes to the brain or spinal cord damage induced by hypoxia-ischemia, trauma, or seizures, and may also play a role in the pathogenesis of some neurodegenerative diseases, such as Huntington's disease or motor neuron disease. Prior work from the laboratory implicated calcium overload and NMDA receptor activation in pathogenesis of excitotoxic cell death. In more recent years, investigation has broadened to include other perturbations in cationic homeostasis, the interrelationship between excitotoxicity and apoptosis, and downstream injury pathways including free radical generation. My colleagues and I hypothesize that endogenous brain zinc stores may also mediate neuronal death under some pathological conditions, and that potassium efflux via voltage- or glutamate-gated channels may promote neuronal apoptosis. We have also examined the possibility that certain growth factor may enhance, rather than reduce, excitotoxic neuronal death. A recent line of research, conducted in collaboration with several other laboratories at Washington University and elsewhere, explores strategies for promoting recovery after rodent spinal cord injury utilizing stem cell transplantation. choid@neuro.wustl.edu 314-362-7175 CONTACT INFORMATION E-mail: wildersp@neuro.wustl.edu (314) 362-9460 Fax: (314) 362-9462 Washington University School of Medicine 660 S. Euclid Campus Box 8111 St. Louis, MO 63110 ********************************************************* RTM: Zomig.com: aspartame in AstraZeneca Zomig-ZMT for migraine 4.21.2 rmforall http://www.astrazeneca-us.com/ http://www.astrazeneca-us.com/contactus/contact_form.asp AstraZeneca Pharmaceuticals LP 1800 Concord Pike P.O. Box 15437 Wilmington, DE 19850 (302) 886-3000 fax (800) 456-3669 fax (302) 886-2972 AstraZeneca LP 725 Chesterbrook Blvd. Wayne, PA 19087 (610) 695-1000 (800) 942-0424 AstraZeneca LP 50 Otis St. Westborough, MA 01581 (508) 366-1100 (800) 237-8898 fax (508) 366-7406 http://www.zomig.com/ 800-456-3669, ext. 62231 [Zolmitriptan] http://www.zomig.com/professional_html/mono_pharma.asp Because ZOMIG is prescription medicine, only your doctor or health care provider can help you decide whether it's right for you. Patients with the inability to process the amino acid phenylalanine should be aware that each 2.5 mg and 5 mg ZOMIG-ZMTTM(zolmitriptan) Orally Disintegrating Tablet contains 2.81 mg and 5.62 mg of phenylalanine(a component of aspartame), respectively. [[Zomig-ZMT thus contains 5.6 and 10.2 mg aspartame, whereas a 12-oz diet soda has 200 mg.] ********************************************************* Sh0shanna@aol.com: aspartame in medicines, vitamins, food 5.10.99 Message: 15 on aspartame@onelist.com discussion group Date: Mon, 10 May 1999 19:53:38 EDT From: Sh0shanna@aol.com Subject: ASPARTAME in Medicines & Children's Vitamins & Food Here is a partial list: [The aspartame content is twice the phenylalinine content.] Use of aspartame by some pharmaceutical companies. Note: Too many companies do not reply concerning their use of aspartame. Johnson and Johnson Pharmaceuticals: Mylanta Natural Fiber Supplement, Sugar Free. Lederle Laboratories: Centrum,Jr vitamins contain aspartame. McNeil Consumer Products: Childrens TYLENOL acetaminophen Fruit Flavored Chewable Tablets Childrens TYLENOL acetaminophen Grape Flavored Chewable Tablets Childrens TYLENOL acetaminophen Cold Multi-Symptom Chewable Tablets Junior Strength TYLENOL acetaminophen Fruit Flavored Chewable Tablets Junior Strength TYLENOL acetaminophen Grape Flavored Chewable Tablets PEDIACARE Cold-Allergy Tablets for Ages 6 to 12 PEDIACARE Cough-Cold Tablets for Ages 6 to 12 PEDICARE Childrens Cold Relief Tablets TYLENOL Cold and Flu Hot Medication TYLENOL Cold and Flu No Drowsiness Formula Hot Medication Childrens Chewable CO-TYLENOL Miles Incorporated: ALKA-SELTZER PLUS Night-time Cold Medicine ALKA-SELTZER PLUS Cold and Cough Medicine ALKA-SELTZER PLUS Sinus Allergy Medicine ALKA-SELTZER Cherry flavored BUGS BUNNY Vitamin Products (ALL) FLINTSTONES Plus Calcium Multivitamin Supplement FLINTSTONES Complete Multivitamin Supplement FLINTSTONES Childrens Chewable Multivitamin A.H. Robbins Company, Inc: DIMETAPP Cold and Allergy Chewable Tablets Bristol-Myers Squibb Company: The following BMS product contains aspartame: CEFZIL Mead Johnson Nutritionals: TEMPRA 3 Chewable Tablets, 80mg acetaminophen tablet (3.3 mg phenylalinine/tab) TEMPRA 3 Double Strength Chewable Tablets, 160 mg acetominophen (6.6 mg Phen/tab) Glaxo Pharmaceuticals: Zantac Efferdose Bio-Pharmaceutics: Childrens Chewable Acetiminophen Pennex Products: American Stores: SKAGGS ALPHA BETA Childrens Pain Reliever Consumer Value Stores: CVS Childrens Non-Aspirin Pain Reliever Drug Guild Dist: DRUG GUILD childrens anti-pain Chewable Tablets First Nat’l Supermarkets: FINAST Childrens Non-Aspirin Pain Reliever Greenbax Enterprises: PRICE-WISE Childrens Non-Aspirin Pain Reliever Hannaford Bros: SHOP’N SAVE Childrens Non-Aspirin Pain Reliever J.C.Penny: TREASURY Childrens Chewable Non-Aspirin Pain Reliever Kinney Drugs: KINNEY”S Childrens Chewable Non-Aspirin Pain Reliever LaVerdiere’s Super Drug: LV ACTION SOOTHSALL Childrens Non-Aspirin Legend Pharmaceuticals: LEGEND Childrens Chewable Non-Aspirin P.R. Malone & Hyde: HYDE PARK Childrens Non-Aspirin Pain Reliever Marsh Supermarkets: MARSH Childrens Non-Aspirin Pain Reliever Osco Drug: OSCO Childrens Chewable Non-Aspirin Pain Reliever Pay'n Save Stores: PAY’N SAVE Childrens Chewable Non-Aspirin Pain Reliever Penned Products: GOOD HEALTH Childrens Non-Aspirin Pain Reliever Peoples Drug Stores: PEOPLES Childrens Chewable Non-Aspirin Pain Reliever Piggly Wiggly Corp: PIGGLY WIGGLY Childrens Chewable Non-Aspirin P.R. Rite Aid Corp.: RITE AID Childrens Aceteminophen Non-Aspirin Pain Reliever Scriver: SUPER TRU Childrens Non-Aspirin Pain Reliever (Acetaminophen) Wegman’s Food Markets: WEGMANS Childrens Chewable Acetaminophen Whitehall Labs: Childrens Anacin-3 Chewable Tablets Cenci Powder: NATURLAX Natural Fiber Laxative LIFE LINE Natural Fiber Laxative H & PC Products: SUGAR FREE METAMUCIL Eckerd: ECKERD Sugar Free Natural Fiber Laxative Fay's: FAY'S Sugar Free Natural Vegetable Laxative Longs: LONGS Sugar Free Natural Vegetable Powder Laxative Payless: PAYLESS Sugar Free Natural Vegetable Powder Laxative Perrigo: Sugar Free Natural Vegetable Powder Perry: PERRY Drug Stores Sugar Free Natural Veg.Powder Bulk Laxative Raley’s: RALEY’S Sugar Free Natural Vegetable Powder Rite Aid: RITE AID Sugar Free Regular Flavor Nat.Veg.Bulk Powder Squibb: SQUIBBCARE Sugar Free Natural Fiber Laxative Thrifty: THRIFTY Sugar Free Natural Vegetable Laxative Hall Laboratories: HEALTH BALANCE Childrens Chewable Multivitamin ZOO CHEWS Animal-Shaped Chewable Multivitamin Mediguard: MEDIGUARD Childens Multivitamin Supplement (Cherry,Orange and Grape) Equate: EQUATE Chewable Vitamins Animal-Shaped (with Iron) Meijer: MEIJER CIRCUS SHAPES (Complete with Calcium,Iron and Minerals) MIEJER CIRCUS SHAPES (with Iron) Perrigo: ANIMAL SHAPES Chewable Vitamins Plus Extra C ANIMAL SHAPES Chewable Vitamins Complete ANIMAL SHAPES Chewable Vitamins With Iron Raley's: Childrens Chewable Vitamins With Iron Lifeline Nutritional: Lucky Stores: Mediguard Childrens Multivitamin Supplement with Iron P.Leiner: Carls Drug Co: CARLS DRUG Childrens Chewable Multivitamin Malone & Hyde: HYDES PARK Childrens Chewable Multivitamin Hills Dept Stores: HILLS Childrens Chewable Multivitamin Kent Co: DART Childen’s Chewable Multivitamin Big B Discount Drugs: BIG B Childrens Chewable Multivitamin LKS Products, Inc: MEDI-GUARD Childrens Chewable Multivitamins Revco Drug Stores: REVCO Childrens Chewable Multivitamins Longs Drug Stores: LONGS Children’s Chewable Multivitamin Gray Drug Fair, Inc: GRAY DRUG FAIR Childrens Chewable Multivitamin Pharmavite Corp: ECKARD DRUG: Childrens Chewable Multivitamin LONGS DRUG Childrens Chewable Multivitamin REFERENCES Data obtained from Aspartame Research Group forwarded to Leading Edge Research. http://www.cco.net/~trufax/research/f26.html Much more good info at: http://www.trufax.org/menu/chem.html#aspartame http://www.cco.net/~trufax/menu/food.html#aspartame ********************************************************* Subject: Aspartame Support] Wrigley's gums Date: Sat, 27 Jul 2002 15:12:32 -0500 From: "Mitchells" To: I've noticed that Wrigley's gums are getting new packaging and the labels on Doublemint, Juicy Fruit, Spearmint & Winterfresh include Aspartame & Acesulfame-K. ********************************************************* http://www.nutrasweet.com/search/index.asp Consumer Center All About NutraSweet NutraSweet Content For specific information regarding individual products, the manufacturer should be contacted as exact formulations differ with each manufacturer. Here is approximate aspartame content in several product categories. Product Category Serving Size Approx. Aspartame Content Carbonated Beverage 12 ounces 180 mg Gelatin Dessert 4 ounces 95 mg Powdered Drink 8 ounces 120 mg Hot Chocolate 6 ounces 50 mg Pudding Dessert 4 ounces 25 mg Frozen Novelty 2-3 ounces 50 mg Fruit Drink (10% juice) 6 ounces 70 mg Breath mint 1 mint 1.5 mg Vitamins 1 vitamin 4 mg Ice Cream 4 ounces 50 mg Yogurt 8 ounces 124 mg Gum 1 stick 6-8 mg ********************************************************** 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 rmforal N Engl J Med 1987 Nov 5;317(19):1181-5 Aspartame and susceptibility to headache. Schiffman SS, Buckley CE 3d, Sampson HA, Massey EW, Baraniuk JN, Follett JV, Warwick ZS 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] ********************************************************* http://nancymarkle.com/headach.txt James B. Hays, MD: 10 cases of aspartame toxicity, 9 with headache [Extracts] With few exceptions these symptoms appear as a recognizable pattern or syndrome with some symptoms peculiar to Aspartame ingestion. Ten patients were noted since 1986 whose symptoms were notable enough to keep a record and report them as a series. Only subjects who resided in Brown County, Texas, are reported here and subjects of suspected lack of objectivity are excluded. The length of exposure to diagnosis varied from about five years to two weeks. The amount of ingestion varied from two drinks daily to two or three liters of diet drinks plus Equal added to lots of tea plus assorted junk food plus sugarless gum-- all in the vain attempt to lose weight.... Since all but one of these patients had severe headaches , these headaches were examined in detail. The headaches were bilateral, severe, generally daily or at least on days that significant amounts of Aspartame were ingested. The headaches did not resemble migraine at all-- they rarely were described as throbbing and were at best described as tension, fatigue, caffeine withdrawal type headaches and a big hangover all combined.... Each patient either accidentally, of their own volition or asked by myself, discontinued the drug and definitely noted cessation or marked abatement of symptoms, and after returning to consume additional Nutrasweet after a definite one to two weeks abstinence all had marked to severe return of symptoms within an hour to a few days of exposure.... http://www.brmc-cares.com/pages/physicianref.html Brownwood Regional Medical Center GENERAL PRACTICE James B. Hays, MD 120 South Park, Suite F Brownwood, Tx 76801 915-646-2523 ********************************************************* 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 ***********************************************************