Epidemiologic studies of the association of L-tryptophan with the eosinophilia-myalgia syndrome: A critique

In 1989 and 1990, 2 reports of a new disease labeled the eosinophilia-myalgia syndrome (EMS) and attributed to L-tryptophan (LT) were published. In subsequent studies a putative contaminant was implicated. In this review the following studies are considered: the initial 2 reports of the overall association, one report of an association between LT and eosinophilic fasciitis, and one report describing the scale of the apparent epidemic of LT induced EMS. Of the 2 initial studies, one included previously reported exposed cases, failed to rule out the possibility that early symptoms of EMS could have caused LT use rather than the reverse, and failed to adhere to the methods, as published. The 2nd study has not been published in a peer reviewed journal. The study of eosinophilic fasciitis was subject to information bias and misclassification of the timing of LT use. The apparent epidemic could have been an artefact of waxing and waning enthusiasm for reporting exposed cases to an EMS registry, corresponding with the timing and the amount of publicity given to the topic. The questionable validity of these studies considerably weakens the claim that LT or a contaminant caused EMS.