The Metabolites in the Tryptophan Degradation Pathway Might Be Useful to Determine the Tolerable Upper Intake Level of Tryptophan Intake in Rats1–3

Abstract

ʟ-Tryptophan (ʟ-Trp) is a rate-limiting amino acid for growth in people from underdeveloped countries. Because ʟ-Trp is also a precursor to nicotinamide, administration of the free form of ʟ-Trp is a very good method of preventing pellagra. Furthermore, ʟ-Trp has shown some effectiveness for the treatment of a variety of other conditions typically associated with low serotonin levels in the brain. Therefore, information about the no-observed-adverse-effect level and lowest-observed-adverse-effect level of ʟ-Trp is needed. However, it is not possible to experimentally obtain such data in humans due to ethical considerations. The aim of the present workshop was to identify biomarkers that could be used before the appearance of adverse effects of ʟ-Trp. We reviewed the published research using rats to develop an index of the metabolic upper intake level for ʟ-Trp to be used instead of the tolerable upper intake level (UL). These results show that the urinary excretory ratio of anthranilic acid:kynurenic acid is potentially the most sensitive and appropriate surrogate breakpoint index to predict the UL of ʟ-Trp.