Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers

J Neurochem. 1999 Apr;72(4):1641-7. doi: 10.1046/j.1471-4159.1999.721641.x.


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 approximately 2 h following ingestion of the TRP-free amino acid drink and were lowest approximately 6 h after ATD; CSF TRP and 5-HIAA were decreased at 2.5 h and approximately 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.

MeSH terms

  • Adult
  • Alcoholism / metabolism
  • Amino Acids / administration & dosage
  • Brain / metabolism
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Diet
  • Female
  • Humans
  • Hydroxyindoleacetic Acid / blood*
  • Hydroxyindoleacetic Acid / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Serotonin / biosynthesis
  • Tryptophan / blood*
  • Tryptophan / cerebrospinal fluid*
  • Tryptophan / deficiency


  • Amino Acids
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Tryptophan