Does 5-Hydroxytryptophan Cause Acute and Chronic Toxic Perturbations in Rats?

Abstract

In 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) occurred in the United States that was attributed to contaminated l-tryptophan (LT). Features of tryptophan-induced EMS included debilitating myalgia and marked peripheral eosinophilia. Although the contaminant(s) was found only in the product produced by a single manufacturer (Showa Denko), all LT was withdrawn from the market and replaced by 5 hydroxytryptophan (5HTP). The belief was that the latter should not contain the implicated contaminant(s), because it was manufactured by a process entirely different from the banished LT. Nevertheless, in 1994 a case diagnosed as EMS appeared. Although the exact causative factor(s) in LT and the possible 5-HTP-induced EMS are uncertain, many reported finding “Peak E” in contaminated LT and the presence of “Peak X” in the 5-HTP of the 1994 case. The latter finding led some to assume that Peak X was a potential pathological agent in 5-HTP that might cause future cases of EMS. To determine whether 5-HTP could cause EMS, we followed 120 male Sprague-Dawley rats, 7 to 8 weeks of age (body weight 200–250 g), for 1 year. They were divided into three groups of 40. One group acted as control, drinking only water; a second group received a low dose of 5-HTP in their drinking water (87.5 mg/dL); and the last group drank a high dose of 5-HTP, 875 mg/dL. No significant differences in the body weights of these three groups of animals were observed over the year. After 2 months, systolic blood pressures (SBP) in the 5-HTP groups were significantly lower for the duration of the study. At the end of 12 months, SBP of the control group averaged 140 mm Hg, the low-dose 5-HTP group averaged 133 mm Hg, and the high-dose group averaged 125 mm Hg. Even though enough 5-HTP was given to cause a physiological response, no significant differences were found in the hematological values, including eosinophil count. Also, no significant differences were found in hepatic and renal values. In the histological studies, no treatment-related changes were noted in the hearts, livers, pancreases, leg striated muscles, and small intestines. In particular, there was no evidence of eosinophilic infiltration and fascial/perimysial inflammation. Accordingly, no significant evidence of EMS was seen in rats receiving high-dose 5-HTP for 1 year.