Time-restricted eating modifies exercise-induced changes in kynurenine metabolism in older women

Time-restricted eating (TRE) has emerged as a promising non-pharmacological intervention capable of improving metabolic health and modulating circadian biology. Exercise induces dynamic shifts in the tryptophan-kynurenine (TRP-KYN) pathway, a metabolic axis implicated in ageing, inflammation, and neurocognitive function. Whether TRE alters basal kynurenine metabolism and/or modifies the acute metabolic response to exercise in older women remains unclear. In this single-arm interventional study, 66 women performed a single exercise session, and serum samples were collected before and after exercise. Subsequently, 30 women were randomly selected to participate in a 12-week time-restricted eating (TRE) protocol consisting of a 10-hour eating window and a 14-hour fasting period. Venous blood samples were collected at four time points: pre- and post-exercise at baseline, and pre- and post-exercise following the intervention. Participants performed a supervised high-intensity interval cycling session. Serum concentrations of tryptophan and downstream kynurenine pathway metabolites were quantified using validated LC–MS/MS methodology. 21 participants with complete metabolite data at all four timepoints were included in the final repeated-measures analysis. At baseline, acute exercise significantly increased circulating kynurenic acid (KYNA), xanthurenic acid (XANA), and selected pathway ratios, without affecting upstream kynurenine (KYN) or 3-hydroxykynurenine (3-HK). Following 12 weeks of TRE, resting concentrations of KYN and 3-hydroxyanthranilic acid (3-HAA) were reduced, while the acute exercise response was enhanced for KYNA and XANA. Additionally, the balance between downstream neuroactive metabolites and upstream intermediates shifted after TRE, indicating an altered circulating kynurenine metabolite profile. This study provides evidence that time-restricted eating (TRE) induces metabolic changes in the kynurenine pathway that partially overlap with those observed following exercise training in older women. These findings suggest that nutritional timing may represent a promising non-pharmacological approach for modulating metabolic pathways associated with exercise adaptation. The trial was registered as a clinical trial (NCT05229835, date of first registration 14/01/2022, direct link https://classic.clinicaltrials.gov/ct2/show/NCT05229835 ).