Safety of 5-hydroxy-L-tryptophan

Toxicol Lett. 2004 Apr 15;150(1):111-22. doi: 10.1016/j.toxlet.2003.12.070.


5-Hydroxy-L-tryptophan (5-HTP) is the immediate precursor in the biosynthesis of 5-hydroxy-tryptamine (5-HT; serotonin) from the essential amino acid L-tryptophan (L-Trp). The use of L-Trp as a dietary supplement was discontinued in 1989 due to an outbreak of eosinophilia-myalgia syndrome (EMS) that was traced to a contaminated synthetic L-Trp from a single manufacturer. 5-HTP has since become a popular dietary supplement in lieu of the removal of L-Trp from the market. Because of its chemical and biochemical relationship to L-Trp, 5-HTP has been under vigilance by consumers, industry, academia and government for its safety. However, no definitive cases of toxicity have emerged despite the worldwide usage of 5-HTP for last 20 years, with the possible exception of one unresolved case of a Canadian woman. Extensive analyses of several sources of 5-HTP have shown no toxic contaminants similar to those associated with L-Trp, nor the presence of any other significant impurities. A minor chromatographic peak (peak X) reported in some 5-HTP samples lacks credibility due to chromatographic artifacts and infinitesimal concentrations, and has raised undue speculations concerning its chemistry and toxicity.

Publication types

  • Case Reports
  • Review

MeSH terms

  • 5-Hydroxytryptophan / adverse effects*
  • 5-Hydroxytryptophan / pharmacology
  • 5-Hydroxytryptophan / toxicity
  • Adult
  • Animals
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / toxicity
  • Depressive Disorder / drug therapy
  • Drug Contamination
  • Eosinophilia-Myalgia Syndrome / chemically induced
  • Eosinophilia-Myalgia Syndrome / epidemiology
  • Female
  • Humans
  • Legislation, Drug
  • Nonprescription Drugs / adverse effects
  • Nonprescription Drugs / toxicity
  • Tryptophan / adverse effects
  • Tryptophan / toxicity
  • United States
  • United States Food and Drug Administration


  • Antidepressive Agents
  • Nonprescription Drugs
  • Tryptophan
  • 5-Hydroxytryptophan