A Single Exercise Session Elicits a Transient Kynurenine Metabolic Signature in Health and Disease: A Systematic Review and Meta-Analysis.

Abstract

Tryptophan (TRP) is primarily metabolized via the kynurenine (KYN) pathway, which plays a central role in energy homeostasis, as well as immune, inflammatory, and neurobiological regulation. Although a single exercise session may modulate this pathway, the magnitude and consistency of these responses remain unclear. Therefore, this meta-analysis aimed to synthesize acute exercise-induced changes in KYN pathway metabolites. PubMed, Web of Science, and Scopus were searched from inception to June 2026. Clinical trials evaluating the effects of a single exercise session on circulating TRP and KYN pathway metabolites were included. Random-effects meta-analyses were performed using standardized mean differences (Hedges' g). Outcomes were analyzed separately for immediate post-exercise responses (≤ 5 min) and recovery responses (> 5 min to 3 h). Prespecified subgroup analyses examined population characteristics, training status, and exercise modality. Of 3203 records, 24 clinical trials (n = 695) were included in the systematic review, and 20 provided data for meta-analysis. Immediately after exercise, TRP decreased, whereas KYN, KYN/TRP, kynurenic acid (KYNA), and quinolinic acid (QA) increased. During recovery, reductions in TRP and elevations in KYN/TRP persisted, whereas KYN and QA returned toward baseline. KYNA remained elevated, while QA/KYNA remained unchanged. Subgroup analyses suggested larger responses in healthy individuals, trained participants, and following aerobic exercise, particularly for TRP and KYNA. Exercise induces heterogeneous changes in KYN metabolism, characterized by reduced TRP and increased KYN/TRP ratio and downstream metabolites. These responses are transient and context-dependent, reflecting acute changes in metabolic flux rather than sustained pathway remodeling. Trial Registration: PROSPERO, identifier CRD42022351481.