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How do we know MSG causes unwanted observable reactions?

Evidence of monosodium glutamate-induced adverse reactions comes from epidemiological studies that demonstrate that monosodium glutamate causes adverse reactions in humans; from studies and case reports published by concerned physicians; and from reports of consumers who find their symptoms abate after discontinuing use of products that contain monosodium glutamate, but reoccur when monosodium glutamate is ingested.

Studies completed in the 1970's demonstrated that at least 25% of the population react to monosodium glutamate in processed food at that time (1-4).

Today, we recognize that there are at least 40 ingredients that contain the same manufactured amino acid that causes the adverse reactions caused by monosodium glutamate. The reactions to this processed (manufactured) free glutamic acid range from mild and transitory to debilitating and/or life threatening, and include skin rash, simple headache, nausea/vomiting, asthma-like symptoms, migraine headache, tachycardia, panic attack, anaphylactic shock, seizures, depression, and more. A link to the list of the adverse reactions compiled by the Truth in Labeling Campaign follows at the end of this paper.

The first published report of an adverse reaction to monosodium glutamate appeared in 1968 in a letter published in The New England Journal of Medicine (175). Dr. Robert Ho Man Kwok, senior research investigator at the National Biomedical Research Foundation in Silver Spring, Maryland, told his colleagues that for several years, since he had been in the United States, he had experienced a strange syndrome whenever he ate in a restaurant serving Northern Chinese food--an experience he had never experienced in his native land. He reported that 15 or 20 minutes after beginning to eat, he experienced "...numbness at the back of the neck, gradually radiating to both arms and the back, general weakness and palpitation." The syndromes lasted about two hours. He had never heard of such a syndrome until he received complaints of the same symptoms from both medical and nonmedical friends. Through The New England Journal of Medicine, he asked his colleagues in the medical field if they might be interested in seeking more information about this "rather peculiar" phenomenon which someone at the journal dubbed, "Chinese Restaurant Syndrome."

Ten people responded almost immediately. Eight had experienced similar, but not necessarily identical reactions when dining in certain Chinese restaurants (179-186) and, as in Kwok's case, had no clear cut notion of what the causative factor might be; and two had experienced similar reactions which they traced to probable muscarine poisoning (187) or to the potent nonprotein neurotoxin, tetrodotoxin found in the puffer fish (188).

While Kwok offered that the syndrome might be attributable to the ingestion of monosodium glutamate, a subsequent issue of The New England Journal of Medicine carried letters from both Schaumburg and Byck (189) and a group of New York University pharmacology students who had studied the condition for an elective project (190) who stated, unequivocally, that the syndrome which Kwok and his friends had experienced was a reaction to ingesting monosodium glutamate.

Schaumburg and Byck pointed out that the reaction being discussed was well known to experienced allergists and Chinese-restaurant owners; and they offered preliminary hypotheses pertaining to the nature of the reaction (189). Ambos et al. added that although the reaction had not been cited in the literature, it had been clearly recognized by "...certain persons and within some families" (190). There was general agreement that monosodium glutamate caused a reaction in sensitive individuals which most often consisted of the reactions mentioned by Kwok.

Schaumburg and Byck mentioned that syncope, tachycardia, lacrimation, fasciculation and nausea were noticed among the people they had found to be monosodium glutamate sensitive but at the time, they were attributed to causes other than monosodium glutamate. (At the time, no one dreamed that monosodium glutamate would be neurotoxic.) Onset time for the adverse reactions being considered as possible reactions to monosodium glutamate was 10 to 25 minutes with a duration of 45 minutes to 2 hours. Schaumburg mentioned that 5 grams of monosodium glutamate would produce a reaction in a sensitive individual. Ambos et al. indicated that 2 teaspoons per 6-ounce glass of tomato juice was needed to provoke a reaction in females, while 4 teaspoons per 6 ounce glass was needed to provoke a reaction in males (190).

In 1969, Schaumburg et al. reported results of studies they had undertaken. This time, both headache and chest pain were added to the symptom list, and a point was made of the fact that there is considerable variability in threshold dose among individuals. Experiments were done with a wide range of test materials and a variety of experimental conditions. Schaumburg et al. concluded, "We now have shown that [monosodium glutamate] can produce undesirable effects in the amounts used in the preparation of widely consumed foods" (191).

Additional case reports presented themselves from time to time. In 1972, Upton and Barrows warned that, based on their observations of an epileptic woman, it would seem reasonable to advise patients on diphenylhydantoin to avoid foods rich in monosodium glutamate (192).

From time to time, case reports have been published describing instances of adverse reactions associated with ingestion of monosodium glutamate. There have been reports of tachycardia (213), hyperactive or hysterical activity in children (214-215), paraesthesiae of hands and feet (216), severe "burning" headache (217), severe upper abdominal pain and pressure accompanied by diaphoresis and a burning sensation in the chest (217), angio-oedema (218), and a hypertensive reaction in the form of vascular headache, typical of those seen in patients taking monoamine oxidase inhibitors (219). Ratner et al. report that the initial diagnoses in seven patients whose complaints were eventually resolved as monosodium glutamate sensitivity, were migraine (twice), myocardial infarction, brain tumor, neurosis, functional colitis, and depression (217).

In 1975 Reif-Lehrer wrote to The New England Journal of Medicine, reporting that children react to ingestion of monosodium glutamate, and describing symptoms similar to adults with almost the same degree of prevalence. She presented three cases and discussed the relation between shudder in children, epileptic "seizures", "[monosodium glutamate] shivers", and the fact the glutamic acid has been reported to cause convulsive disorders in animals (220). Subsequently, Andermann, et al., commented on a possible relationship between glutamic acid and essential tremor (221).

During the next two years, Reif-Lehrer published 1) an additional report of children's apparent adverse reactions to monosodium glutamate (222); 2) results of a questionnaire study establishing that 25% of those responding to the questionnaire and 30% of the persons reporting that they had been exposed to Chinese restaurant food reported adverse reactions (223); and 3) a lengthy review and report on the possible significance of adverse reactions to monosodium glutamate in humans (224).

Colman wrote to The New England of Medicine in 1978, reporting two cases of psychiatric reactions to monosodium glutamate (225). Comments and observations also have been published. Neumann reported having seen reactions involving frequent ventricular premature beats. He cautioned that, "Because sensitivity to [monosodium glutamate] is not rare and because of the unpredictable consequences given a damaged, vulnerable, or irritable myocardium, patients with a tendency to rhythm disturbances should be made wary of prefabricated soups, and meat 'tenderizers,' in addition to the fare of Chinese restaurants. Incidentally, the term 'Chinese restaurant syndrome,' while picturesque, is too narrow considering the tons of monosodium glutamate used in less exotic foods. The syndrome should really be termed what it is, an [monosodium glutamate] atopy. And the cardiovascular system is its chief target" (226).

Gore and Salmon observed 55 subjects given randomized monosodium glutamate and placebo trials, and noted that although the reactions to monosodium glutamate were significant, the symptoms recorded were not those of the CRS. They questioned the meaning of reaction to symptoms which were not CRS (Chinese Restaurant Syndrome) (227). Sauber pointed out that the meaning was perfectly clear -- that the symptoms which Gore and Salmon found to be most prevalent, were, indeed, the most prevalent visible effects of monosodium glutamate (228).

Asthma has been studied extensively by Allen (229-230). He explored and discussed the possible relation of monosodium glutamate to asthma, questioning the possible links, and exploring possible mechanisms for a relationship. In a single blind study using 32 subjects with asthma, some of whom had histories of severe asthma after Chinese restaurant or similar meals, he found a dose dependent reaction which in some cases was delayed up to 12 hours (230).

Moneret-Vautrin reported finding a "...very small subset of patients with intrinsic asthma..." with an intolerance to high doses (2.5g) of monosodium glutamate (231).

Fibromyalgia is a common rheumatologic disorder that is often difficult to treat effectively. Smith et al. reported on four patients diagnosed with fibromyalgia syndrome for two to 17 years, all of whom had undergone multiple treatment modalities with limited success. All had completed, or nearly completed, resolution of their symptoms within months after eliminating monosodium glutamate or monosodium glutamate plus aspartame from their diets. All had recurrence of symptoms whenever monosodium glutamate was ingested (232).

The relationship between processed (manufactured) free glutamic acid and migraine headache was explored by Alfred Scopp who, in 1991, published a study entitled "MSG and hydrolyzed vegetable protein induced headache: review and case studies" (233). In 1993, Martinez et al. measured glutamic and aspartic acid levels in plasma and cerebrospinal fluid (CSF) of patients with common and classic migraine during attacks, making comparisons with controls suffering from stress. Plasma levels of amino acids in migraine patients were lower than in controls, while CSF concentrations of glutamic acid were higher in migraineurs than in controls. The authors concluded that "... results suggest an excess of neuroexcitatory amino acids in the [central nervous system] of migraine patients during attacks, possibly favoring a state of neuronal hyperexcitability (234)." Martinez et al. had found a relationship between glutamate levels in the CSF of the central nervous system and migraine headache.

Today, virtually every headache clinic in the United States acknowledges that "processed free glutamic acid" (popularly referred to as MSG) is one of the triggers of migraine headache. According to Scopp (who, at the time, was at the Northern California Headache Clinic), at least 33 per cent of migraine patients have some migraine headaches triggered by free glutamate (235).

Although reports of adverse reactions are growing, there seems to be no incentive to publish case studies or case reports in the medical literature. No one compensates physicians for writing up case studies. Moreover, the FDA has collected, but never solicited, reports of adverse reactions to monosodium glutamate and other free glutamate-containing ingredients, and does not publish those reports that it does receive. There are studies that warn of hazards of food additive MSG and free glutamate ingestion, but they are studies of pathophysiology related to glutamate, not studies of adverse reactions per se. The one exception may be the work of He et al. who found that weight gain and obesity are related to ingestion of monosodium glutamate (236).

Most of the reports of adverse reactions associated with monosodium glutamate in the published literature are reports of badly flawed research claiming to have found no relationship between monosodium glutamate and any sort of adverse reaction to it, all funded, at least in part, by Ajinomoto's International Glutamate Technical Committee and/or others in the glutamate industry. Ironically, those industry-sponsored studies themselves provide examples of adverse reactions following ingestion of monosodium glutamate in monosodium glutamate test.

Industry-sponsored reports that claim to have demonstrated that monosodium glutamate is "safe" far outnumber studies reported by independent researchers. The reason for the discrepancy is simple. Those who generate studies that pretend to find that monosodium glutamate is "safe" are invariably paid to do so, directly or indirectly, by the glutamate industry. But no food or drug company or the U.S. Food and Drug Administration (FDA), is funding research designed to explore the potential toxicity of a food additive. Moreover, people who do studies that displease the industrial giants have been known to be both smeared and harassed. The few published reports of observed adverse reactions to food additives come primarily in the form of letters to the editor, relating clinical observations.

The FDA, both in its Adverse Reactions Monitoring System (ARMS) and elsewhere, has in its files numbers of letters from people reporting their sensitivities to monosodium glutamate and/or the other ingredients that contained processed free glutamic acid. In the Memorandum to the Health Hazards Evaluation Board of the FDA dated October 6, 1989 and June 8, 1990, entitled, "Adverse reactions associated with [monosodium glutamate] ingestion," Linda Tollefson detailed the symptoms that had been reported to ARMS as of each date. The lists included headache, vomiting and nausea, diarrhea, change in heart rate, change in mood quality or level, abdominal pain and cramps, dizziness or problems with balance, localized pain and tenderness, sleep problems, change in vision, fatigue, weakness, change in body temperature, difficulty breathing, local swelling, joint and bone pain, chest pain, change in sensation (numbness, tingling) change in activity level, blood pressure changes, difficulty swallowing, and more.

Tollefson concluded, after considering all of the material available to her, that, "...there was suggest that MSG is a human health hazard." The fact that Tollefson chose to regard all of the cases presented as non-indicative of sensitivity to MSG says nothing about the facts.

Additional reports of adverse reactions have been shared with the Truth in Labeling Campaign. Examples will be found at Consumers Tell Us

Collected Reports of Adverse Reactions Caused by free glutamate
Ingestion of processed free glutamic acid is known to produce a variety of adverse reactions in some people. These reactions, although seemingly dissimilar, are no more diverse than reactions found as side effects of certain neurotrophic (neurological) drugs. We do not know why some people experience reactions and others do not. We do not know whether MSG "causes" the condition underlying the reaction, or whether the underlying condition is simply aggravated by the ingestion of free glutamate or something else. We only know that the reactions listed below are sometimes caused or exacerbated by free glutamate.

All free glutamate that occurs in food as a consequence of manufacture or fermentation causes reactions in people sensitive to free glutamate. That applies to free glutamate found in a plant "growth enhancer" called AuxiGro, and free glutamate found in a variety of other fertilizers and fungicides that have been approved for spraying on growing crops, including crops identified as "organic."

Endocrine disorders, gross obesity, stunted growth, learning disabilities, and behavior disorders caused by free glutamate-induced damage to the endocrine systems of the very young; and glaucoma and retinal degeneration (possibly leading to blindness), are not classified as adverse reactions. When caused by free glutamate their roots lie in the destruction of cells in the central nervous system, possibly years before they are first observed.

Research confirming the fact that free glutamate consumed by laboratory animals causes brain lesions in the area of the hypothalamus and subsequent endocrine disorders, has been replicated many times. Research that has claimed to find that free glutamate (or MSG) is "safe" has always been seriously flawed; and has only been produced, directly or indirectly, by the glutamate industry.

For a list of collected reports of adverse reactions caused by MSG, look here.

1. Reif-Lehrer, L. A questionnaire study of the prevalence of Chinese restaurant syndrome. Federation Proceedings 36:1617-1623,1977.

2. Kenney, RA and Tidball, CS Human susceptibility to oral monosodium L-glutamate. Am J Clin Nutr.25:140-146,1972.

3. Kerr, G.R., Wu-Lee, M., El-Lozy, M., McGandy, R., and Stare, F. Food-symptomatologyquestionnaires: risks of demand-bias questions and population-biased surveys. In: Glutamic Acid: Advances in Biochemistry and Physiology Filer, L. J., et al., Eds. New York: Raven Press, 1979.

4. Schaumburg, H.H., Byck, R, Gerstl, R, and Mashman, J.H. Monosodium L-glutamate: its pharmacology and role in the Chinese restaurant syndrome. Science 163:826-828,1969.

175. Kwok, R.H.M. The Chinese restaurant syndrome. Letter to the editor. N Engl J Med 278: 796, 1968.

179. Schaumburg, H. Chinese-restaurant Syndrome. N Engl J Med 278: 1122, 1968.

180. McCaghren, T.J. Chinese-restaurant syndrome. N Engl J Med 278: 1123, 1968.

181. Menken, M. Chinese-restaurant syndrome. N Engl J Med 278, 1123, 1968.

182. Migden, W. Chinese-restaurant syndrome. N Engl J Med 278: 1123, 1968.

183. Rath, J. Chinese-restaurant syndrome. N Engl J Med 278: 1123, 1968.

184. Beron, E.L. Chinese-restaurant syndrome. N Engl J Med 278: 1123, 1968.

185. Kandall, S.R. Chinese-restaurant syndrome. N Engl J Med 278: 1123, 1968.

186. Gordon, M.E., Chinese-restaurant syndrome. N Engl J Med 278: 1123-1124, 1968.

187. Rose, E.K. Chinese-restaurant syndrome. N Engl J Med 278: 1123, 1968.

188. Davies, N.E. Chinese-restaurant syndrome. N Engl J Med 278: 1124, 1968.

189. Schaumburg, H.H. and Byck, R. Sin cib-syn: accent on glutamate. N Engl J Med 279: 105, 1968.

190. Ambos, M., Leavitt, N.R., Marmorek, L., and Wolschina, S.B. Sin cib-syn: accent on glutamate. N Engl J Med 279: 105, 1968.

191. Schaumburg, H.H., Byck, R., Gerstl, R., and Mashman, J.H. Monosodium L-glutamate: its pharmacology and role in the Chinese restaurant syndrome. Science 163: 826-828, 1969.

192. Upton, A.R.M., and Barrows, H.S. Chinese-restaurant syndrome recurrence. N Engl J Med 286: 893-894, 1972

213. Gann, D. Ventricular tachycardia in a patient with the "Chinese restaurant syndrome." Southern Medical J 70: 879-880, 1977.

214. Asnes, R.S. Chinese restaurant syndrome in an infant. Clin Pediat 19: 705-706, 1980.

215. Cochran, J.W., and Cochran A.H. Monosodium glutamania: the Chinese restaurant syndrome revisited. JAMA 252: 899, 1984.

216. Freed, D.L.J. and Carter, R. Neuropathy due to monosodium glutamate intolerance. Annals of Allergy 48: 96-97, 1982.

217. Ratner, D., Esmel, E., and Shoshani, E. Adverse effects of monosodium glutamate: a diagnostic problem. Israel J Med Sci 20: 252-253, 1984.

218. Squire, E.N. Jr. Angio-oedema and monosodium glutamate. Lancet 988, 1987.

219. Pohl, R., Balon, R., and Berchou, R. Reaction t chicken nuggets in a patient taking an MAOI. Am J Psychiatry 145: 651, 1988.

220. Reif-Lehrer, L. and Stemmermann, M.B. Correspondence: Monosodium glutamate intolerance in children. N Engl J Med 293: 1204-1205, 1975.

221. Andermann, F., Vanasse, M., and Wolfe, L.S. Correspondence: Shuddering attacks in children: essential tremor and monosodium glutamate. N Engl J Med 295: 174, 1975.

222. Reif-Lehrer, L. Letter: A search for children with possible MSG intolerance. Pediatrics 58: 771-772, 1976.

223. Reif-Lehrer, L. A questionnaire study of the prevalence of chinese restaurant syndrome. Fed Proc36:1617-1623, 1977.

224. Reif-Lehrer, L. Possible significance of adverse reactions to glutamate in humans. Federation Proceedings 35: 2205-2211, 1976. 225. Colman, A.D. Possible psychiatric reactions to monosodium glutamate. N Engl J Med 299: 902, 1978.

226. Neumann, H.H. Soup? It may be hazardous to your health. Am Heart J 92:, 266, 1976.

227. Gore, M.E., and Salmon, P.R. Chinese restaurant syndrome: fact or fiction. Lancet 1(8162): 251, 1980.

228. Sauber, W.J. What is Chinese restaurant syndrome? Lancet 1(8170): 721-722, 1980.

229. Allen, D.J., and Baker, G.J. Chinese-restaurant asthma. N Engl J Med 305: 1154-1155, 1981.

230. Allen, D.H., Delohery, J., & Baker, G.J. Monosodium L-glutamate-induced asthma. Journal of Allergy and Clinical Immunology 80: No 4, 530-537, 1987.

231. Moneret-Vautrin, D.A. Monosodium glutamate - induced asthma: Study of the potential risk in 30 asthmatics and review of the literature. Allergic et Immunologie 19: No 1, 29-35, 1987.

232. Smith, J.D., Terpening, C.M., Schmidt, S.O.F., and Gums, J.G. Relief of fibromyalgia symptonsfollowoing discontinuation of dietary excitotoxins. The Annals of Pharmacoltherapy. 35: (6) 702-706.

233. Scopp, A.L. MSG and hydrolyzed vegetable protein induced headache: review and case studies. Headache. 31:107-110, 1991.

234. Martinez, F. et al. Neuroexcitatory amino acid levels in plasma and cerebrospinal fluid during migraine attacks. Cephalalgia. 13: 89-93, 1993.

235. Scopp, A. Personal communication. June 17, 2002.

236. He K, Zhao L, Daviglus ML, et al. Association of Monosodium Glutamate Intake With Overweight in Chinese Adults: The INTERMAP Study. Obesity. 16(8): 1875-1880, 2008. Epub 2008 May 22.


The truth, the whole truth, and nothing but the truth about MSG and manufactured free glutamate