Effects of Acute Tryptophan Depletion on Plasma and Cerebrospinal Fluid Tryptophan and 5‐Hydroxyindoleacetic Acid in Normal Volunteers

: Brain serotonin synthesis and metabolism (turnover), as indicated by CSF concentrations of 5‐hydroxyindoleacetic acid (5‐HIAA), may depend on plasma concentrations of the essential amino acid L‐tryptophan (TRP). We investigated the biochemical effects of acute plasma TRP depletion (ATD) in normal volunteers undergoing a 36‐h CSF collection via lumbar drain. Six subjects who were in good health were put on a low‐TRP diet (160 mg/day) 24 h before lumbar puncture; this diet was continued for the first 22 h of the CSF collection. At hour 22, subjects ingested a TRP‐deficient 15‐amino acid drink shown previously to deplete plasma TRP. Total plasma TRP, free plasma TRP, and CSF TRP subsequently decreased 86.3, 86.5, and 92.3%, respectively. CSF 5‐HIAA decreased by 32.8%. Plasma total and free TRP concentrations were both decreased at ∼2 h following ingestion of the TRP‐free amino acid drink and were lowest ∼6 h after ATD; CSF TRP and 5‐HIAA were decreased at 2.5 h and ∼4 h after ATD, respectively. CSF TRP was lowest 8.0 h later. CSF 5‐HIAA continued to decrease 14 h after the TRP‐deficient amino acid drink was given.