Effects of Inhibition of Serotonin Synthesis on 5‐Hydroxyindoleacetic Acid Excretion, in Healthy Subjects

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Abstract
The urinary excretion of 5‐hydroxyindoleacetic acid (5‐HIAA), the main metabolite of serotonin, reflects the content and turnover of gastrointestinal (GI) serotonin. Employing longitudinal measurements of 5‐HIAA, the authors investigated in healthy subjects (n = 43) how manipulations of serotonin synthesis affect GI serotonin. Under conditions of serotonin‐free diets, the intersubject and intrasubject variability (coefficient of variation) for 5‐HIAA excretion averaged 33% and 14%, respectively. Dietary tryptophan restrictions to 50% of minimal daily requirements (which is equivalent to a 10‐fold reduction in baseline tryptophan intake) decreased by half the urinary excretion of 5‐HIAA, irrespective of the caloric content of diet Restoration to the regular tryptophan intake produced a rapid normalization of the 5‐HIAA excretion. Neutral amino acids are known to compete with the intestinal transport absorption mechanisms of tryptophan. Administration of neutral aminoacids (1.8 g, by mouth, three times a day, before each meal) or of carbidopa (50 mg, by mouth, three times a day for 3 days) to a normal tryptophan diet failed to alter significantly the 5‐HIAA excretion. Further, neutral aminoacids failed to enhance the reduction in 5‐HIAA produced by the low‐tryptophan diet. The failure of these treatments to reduce 5‐HIAA excretion could be due to large capacity transport and decarboxylation 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 easiest and most effective method to alter GI serotonin. Finally, interpretation of the urinary levels of 5‐HIAA should take into account not only the amount of serotonin in the diet, but also that of tryptophan.