Effects of tryptophan supplementation and exercise on the fate of kynurenine metabolites in mice and humans

Paula Valente-Silva, Igor Cervenka, Duarte M. S. Ferreira, Jorge C. Correia, Sebastian Edman, Oscar Horwath, Benjamin Heng, Sharron Chow, Kelly R. Jacobs, Gilles J. Guillemin, Eva Blomstrand, Jorge L. Ruas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
64 Downloads (Pure)


The kynurenine pathway of tryptophan (TRP) degradation (KP) generates metabolites with effects on metabolism, immunity, and mental health. Endurance exercise training can change KP metabolites by changing the levels of KP enzymes in skeletal muscle. This leads to a metabolite pattern that favors energy expenditure and an anti-inflammatory immune cell profile and reduces neurotoxic metabolites. Here, we aimed to understand if TRP supplementation in untrained vs. trained subjects affects KP metabolite levels and biological effects. Our data show that chronic TRP supplementation in mice increases all KP metabolites in circulation, and that exercise reduces the neurotoxic branch of the pathway. However, in addition to increasing wheel running, we did not observe other effects of TRP supplementation on training adaptations, energy metabolism or behavior in mice. A similar increase in KP metabolites was seen in trained vs. untrained human volunteers that took a TRP drink while performing a bout of aerobic exercise. With this acute TRP administration, TRP and KYN were higher in the trained vs. the untrained group. Considering the many biological effects of the KP, which can lead to beneficial or deleterious effects to health, our data encourage future studies of the crosstalk between TRP supplementation and physical exercise.

Original languageEnglish
Article number508
Pages (from-to)1-15
Number of pages15
Issue number8
Publication statusPublished - 3 Aug 2021

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Behavior
  • Dietary supplements
  • Energy metabolism
  • Exercise
  • Kynurenine metabolites
  • Skeletal muscle
  • Tryptophan


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