Eosinophilia-myalgia syndrome, and

Figure 1 Biosynthesis of i-tryptophan. (Reproduced from Mayeno AN and Gleich GJ (1994) Eosinophilia-myalgia syndrome and tryptophan production A cautionary taie. Trends in Biotechnology 12 346-352, with permission from Elsevier.)...

Mayeno, A. N. and Gleich, G. J., Eosinophilia-myalgia syndrome and tryptophan production A cautionary tale, Trends Biotechnol., 12, 346, 1994. 

Centers for Disease Control. Eosinophilia-myalgia syndrome and L-tryp-tophan-containing products — New Mexico, Minnesota, Oregon, and New York, Morb. Mort. Wkly. Rep., 38, 785,1989. 

Kaufman, L. D., Gruber, B. L., Gomez-Reino, J. J., and Miller, F., Fibrogenic growth factors in the eosinophilia-myalgia syndrome and the toxic oil syndrome, Arch. Dermatol., 130, 41, 1994. 

In 1981-1982, an epidemic spread across Spain, which was eventually labelled the toxic oil syndrome by the World Health Organization (WHO). In less than two years, at least 20 096 people were afflicted by and 356 people died from toxic oil syndrome (Philen et al., 1997 Philen Dicker, 2000). Women, especially those less than 40 years of age, were affected more severely than men 61% of the victims and 66% of the deaths were women (Sanchez-Porro Valades et al., 2003). Toxic oil syndrome has striking similarities to autoimmune diseases, particularly scleroderma. In addition, it resembles eosinophilia myalgia syndrome and diffuse fasciitis with eosinophilia. Toxic oil syndrome-associated manifestations evolved from initiating vasculitis to eosinophilia in the acute phase and then sicca syndrome, neuropathy, scleroderma, Raynaud phenomenon, and musculoskeletal inflammation in the chronic phase (Kaufman Krupp, 1995). More than 70% of toxic oil syndrome patients presented with eosinophilia, regardless of age or sex. 

The eosinophilia myalgia syndrome (EMS) is a complex systemic syndrome with inflammatory and autoimmune components that affects the skin, fascia. 

Add tryptophan to a standard antidepressant (usually an SSRI). There is a danger that the serotonin syndrome may occur however and occasionally the eosinophilia myalgia syndrome. The symptoms that occur with increasing severity are restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions, death. 

Sullivan, E.A., Kamb, M.L., Jones, J.L., Meyer, P., Philen, R.M., Falk, H., and Sinks, T. (1996) The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina. Arch Intern Med 156 973-975. 

Limited evidence indicates that the amino acid precursor of 5-HT, l -tryptophan, may be useful, alone or in combination with other antimanic agents to enhance overall efficacy. Contaminants in the production of this agent led to several cases of the eosinophilia myalgia syndrome (EMS) and its removal from the market for several years. 

The reliability and consistency of commercial melatonin has been questioned (3). One group analysed three commercial melatonin formulations and identified analogues of the contaminant of L-tryptophan compounds implicated in an epidemic of eosinophilia-myalgia syndrome in the 1980s (27). There have been no reports of this condition associated with melatonin consumption, but food supplements are not required to comply with the same manufacturing and monitoring quality control standards as drugs. 

Another case, much more serious and also more pertinent to the chemical process development area, occurred in 1989 when over 1600 people became ill with eosinophilia-myalgia syndrome (EMS) and 38 died, worldwide, after taking l-tryptophan (Trp) manufactured by one producer in Japan. Prior to the outbreak, this producer whose Trp met the >98.5% purity specification had decided to employ a new genetically modified strain of the established Bacillus amyloliquefaciens and also to halve the amount of activated charcoal used in the purification step. These changes cause the Trp product to become contaminated with several new impurities, principally I to III, all associated to some extent (using a crude animal model) with EMS.5... 

The syndrome appears to be only part of a spectrum of adverse effects associated with tryptophan (15). There has been much discussion, but finally it appears that the links are causal, as consistent findings were found in multiple independently conducted studies and the incidence of eosinophilia-myalgia syndrome in the USA fell abruptly once tryptophan-containing products were recalled (16). 

Varga J, Uitto J, Jimenez SA. The cause and pathogenesis of the eosinophilia-myalgia syndrome. Ann Intern Med 1992 116(2) 140-7. 

Kilbourne EM, Philen RM, Kamb ML, Falk H. Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome. J Rheumatol Suppl 1996 46 81-8. 

Another issue with safety of dietary supplements is the purity of the ingredients. The supplements are not required to go through any control measures before they are put on the market unlike drugs. Cases such as the L-tryptophan one in 1989 are therefore subject to be repeated. The impurities of this product led to an epidemic of eosinophilia-myalgia syndrome, with 1500 reported cases and 37 deaths. 

Occasional + +, common + + +, very common. Reproduced from Varga J (1993) L-Tryptophan-associated eosinophilia-myalgia syndrome Clinical and pathological features of an evolving new disease and current concepts of etiology. Journal of Intensive Care Medicine 8 229-242. 

Naylor S, Williamson BL, Johnson KL, and Gleich GJ (1999) Structural characterization of case-associated contaminants peak G and FF in L-tryptophan implicated in eosinophilia-myalgia syndrome. Advances in Experimental Medicine and Biology 467 453—460. 

Philen RM, Hill RH Jr., et al. (1993) Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The eosinophilia-myalgia studies of Oregon, New York and New Mexico. American Journal of Epidemiology 138 154-159. 

See also Blood Cadmium Eosinophilia-Myalgia Syndrome Lead Radiation Toxicology, Ionizing and Nonionizing Tissue Repair Vitamin D. 

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