A Perspective on the Safety of Supplemental Tryptophan Based on Its Metabolic Fates

J Nutr. 2016 Dec;146(12):2601S-2608S. doi: 10.3945/jn.115.228643. Epub 2016 Nov 9.


Over the past 50 y, tryptophan has been ingested in amounts well in excess of its dietary requirement. This use is based on extensive findings that ingesting tryptophan increases brain tryptophan concentrations, which stimulates the synthesis and release of the neurotransmitter serotonin, from which it is derived. Such increases in serotonin function may improve mood and sleep. However, tryptophan ingestion has other effects, such as increasing serotonin production in the gut, increasing serotonin concentrations in blood, stimulating the production of the hormone melatonin (a tryptophan metabolite), stimulating tryptophan metabolism via the kynurenine pathway, and possibly stimulating the production of tryptophan metabolites in the gut microbiome. Several of the kynurenine metabolites have actions on excitatory glutamate receptors in the gut and brain and on cells of the immune system. In addition, metabolites of tryptophan produced by colonic bacteria are reported to cause adverse effects in some species. This review examines each of these tryptophan pathways to determine if any of the metabolites increase after tryptophan ingestion, and if so, whether effects are seen on target body functions. In this regard, recent research suggests that it may be useful to examine kynurenine pathway metabolites and some microbial tryptophan metabolites to determine whether supplemental tryptophan consumption increases their concentrations in the body and amplifies their actions.

Keywords: animals; humans; indoxyl-3-sulfate; kynurenic acid; melatonin; microbiome; quinolinic acid; serotonin; skatole; tryptophan.

Publication types

  • Review

MeSH terms

  • Dietary Supplements*
  • Humans
  • Serotonin / biosynthesis*
  • Tryptophan / administration & dosage
  • Tryptophan / adverse effects*
  • Tryptophan / metabolism*


  • Serotonin
  • Tryptophan