CONTAMINANTS IN L-TRYPTOPHAN ASSOCIATED WITH EOSINOPHILIA-MYALGIA-SYNDROME

In late 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) that resulted in several thousand cases of the syndrome and 36 deaths was r ecognized in the United States. Physicians in New Mexico linked the ep idemic to the ingestion of L-tryptophan (LT). Results of studies indic ated that one or more trace contaminants in LT were likely causes of t he EMS epidemic. Investigators traced the LT that was taken by most pa tients with EMS to a single manufacturer, Showa Denko K.K. of Japan. W e now report results of high performance liquid chromatographic analys is of LT samples from this manufacturer. Three sets of blind-coded sam ples were analyzed: the priority case lot set, which included 54 case- associated LT lots and 50 noncase-associated LT lots that were taken b y case and control subjects who used only one brand of LT; the single lot case set, which included 73 case-associated LT lots and 25 noncase associated LT lots taken by case and control subjects who used only a single lot of LT; and the South Carolina tablet set, which included L T tablets taken by case subjects (n = 26) and by control subjects (n = 52). We statistically compared the concentration of each contaminant in case-associated, noncase-associated, and control samples of each sa mple set. The analyses showed that there were more than 60 minor conta minants in the LT from Showa Denko K.K., and that six of these contami nants were associated with EMS. The structures of three contaminants a re known, but the identities of the other three contaminants are curre ntly unknown. In this paper, we discuss each sample set and results of the analysis of each, the combined results of all sets, the identity of the six contaminants, and implications for future research into the etiology of EMS.