Longitudinal associations of dietary intake with fatigue in colorectal cancer survivors up to 1 year post-treatment, and the potential mediating role of the kynurenine pathway

• DOI: 10.1016/j.bbi.2025.02.003
• Publication Date: 2025-02-07T00:44:32Z
• Authors: Daniëlle D.B. Hol...; Judith J.M. Rijnhart; Martijn J.L. Bours; Eline H. van Roekel; Per M. Ueland; Stéphanie O. Breu...; Maryska L.G. Jans...; Joop L. Konsten; Eric T.P. Keulen; Adrian McCann; Stefanie Brezina; Biljana Gigic; Cornelia M. Ulrich; Matty P. Weijenberg; Simone J.P.M. Eussen
• Keywords: Kynurenine pathway; Longitudinal Study

A healthy diet may help to reduce cancer-related fatigue, but evidence is limited and mechanisms remain unclear. Both fatigue following colorectal cancer (CRC) have been linked metabolites (kynurenines) of the kynurenine pathway (KP). We investigated longitudinal associations between dietary intake potential mediating role KP, in CRC survivors up 1 year post-treatment. Measurements at 6 weeks, months, post-treatment were performed 209 stage I-III survivors. Diet was assessed by 7-day food records. Plasma kynurenines analyzed using LC-MS/MS. Fatigue, including subjective validated questionnaires. To analyse explore mediation we used confounder-adjusted multilevel parallel-multiple mediator models with all included simultaneously, simple established KP ratios estimate total (c: diet-fatigue), direct (c': diet-fatigue, while controlling for mediators), metabolite-specific indirect (ab: diet-metabolite-fatigue), diet-metabolites-fatigue) effects. Higher carbohydrates mono- disaccharides longitudinally associated more higher plant protein, fat, unsaturated fats less (c). Most remained statistically significant after metabolites, except (c'). All simultaneously did not mediate (ab). The kynurenic acid-to-quinolinic acid (KA/QA) ratio significantly mediated intakes carbohydrate, disaccharides, alcohol, magnesium, zinc, whereas HKr association polysaccharide Our findings suggest that carbohydrate greater protein fat are lower While our population, KA/QA mediators several diet-fatigue associations. These results should be repeated larger observational studies.