Vitamin B6 Depletion in Man: Urinary Excretion of Tryptophan Metabolites

Abstract

The effects of vitamin B6 depletion on the metabolism of tryptophan by 6 male subjects were studied during a 55-day experiment. The excretion of several urinary metabolites of the amino acid was measured quantitatively during a 5-day predepletion period when the subjects ate self-selected diets and at intervals throughout the study while they consumed a diet containing only 0.16 mg of vitamin B6 daily. In response to the ingestion of a 2-g supplement of L-tryptophan, the levels of hydroxykynurenine, kynurenine, xanthurenic acid, acetylkynurenine and kynurenic acid were significantly increased in the urine of the subjects as the deficiency was induced. Two subjects showed evidence of abnormal tryptophan metabolism after only 5 days of depletion. The rate and extent to which the individuals exhibited abnormal tryptophan metabolism varied among the 6 males and determined the order in which supplementation with pyridoxine was begun. The excretion of metabolites following tryptophan loading decreased to the normal range when the subjects were given supplemental pyridoxine at a level of 0.6 or 0.9 mg/day. In three of the men, however, tryptophan metabolism did not return to pre-depletion status until the end of the experiment when 50 mg of pyridoxine were administered on 3 consecutive days. The pattern of abnormal tryptophan metabolism observed in this situation was strikingly similar to that found in tuberculosis patients receiving deoxypyridoxine and thus appears to indicate that the pyridoxine antagonist and a dietary deficiency of the vitamin prevent normal functioning of the vitamin B6-dependent enzymes involved in tryptophan metabolism in an analogous manner.