EFFECTS OF INHIBITION OF SEROTONIN SYNTHESIS ON 5-HYDROXYINDOLEACETICACID EXCRETION, IN HEALTHY-SUBJECTS

The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin, reflects the content and turnover of gastroi ntestinal (GI) serotonin. Employing longitudinal measurements of 5-HIA A, the authors investigated in healthy subjects (n = 43) how manipulat ions of serotonin synthesis affect GI serotonin. Under conditions of s erotonin-free diets, the intersubject and intrasubject variability coe fficient of variation) for 5-HIAA excretion averaged 33% and 14%, resp ectively. Dietary tryptophan restrictions to 50% of minimal daily requ irements (which is equivalent to a 10-fold reduction in baseline trypt ophan intake) decreased by half the urinary excretion of 5-HIAA, irres pective of the caloric content of diet. Restoration to the regular try ptophan intake produced a rapid normalization of the 5-HIAA excretion. Neutral amino acids are known to compete with the intestinal transpor t absorption mechanisms of tryptophan. Administration of neutral amino acids (1.8 g, by mouth, three times a day, before each meal) or of car bidopa (50 mg, by mouth, three times a day for 3 days) to a normal try ptophan diet failed to alter significantly the 5-HIAA excretion. Furth er, neutral aminoacids failed to enhance the reduction in 5-HIAA produ ced by the low-tryptophan diet. The failure of these treatments to red uce 5-HIAA excretion could be due to large capacity transport and deca rboxylation systems for tryptophan. Other possibilities are discussed. In summary, dietary tryptophan is essential for the maintenance of GI serotonin. Reductions or increases in dietary tryptophan are the easi est and most effective method to alter GI serotonin. Finally, interpre tation of the urinary levels of 5-HIAA should take into account not on ly the amount of serotonin in the diet, but also that of tryptophan.