The mediating role of the kynurenine pathway in longitudinal associations between dietary intake and quality of life in colorectal cancer survivors up to 12 months posttreatment

Previous research has revealed associations between diet and health-related quality of life (HRQoL), between diet and kynurenine pathway (KP) metabolites (kynurenines), and between kynurenines and HRQoL in colorectal cancer (CRC) survivors. We examined if kynurenines mediate longitudinal associations between diet and HRQoL in CRC survivors up to 12-months posttreatment. Repeated measurements were performed in 209 stage I-III CRC survivors. Diet was assessed by seven-day dietary records. Plasma kynurenines were analyzed using LC-MS/MS. HRQoL outcomes were assessed through the validated EORTC QLQ-C30. We used confounder-adjusted multilevel parallel-multiple mediator models with all kynurenines simultaneously and single mediator models with established KP ratios to estimate total (c:diet-HRQoL), direct (c':diet-HRQoL), metabolite-specific indirect (ab: diet-metabolite-HRQoL), and total indirect (ab:diet-metabolites-HRQoL) effects. Higher carbohydrate intake was associated with worse role functioning, while higher fiber, alcohol, and zinc intake, and better adherence to the Dutch Healthy Diet (DHD) recommendations were associated with better physical and role functioning (c-path). Associations of fiber and DHD with HRQoL remained statistically significant after controlling for all KP metabolites (c'-path). All kynurenines simultaneously only mediated associations of higher carbohydrate intake with worse role functioning, and of higher alcohol intake with better physical functioning (ab). The kynurenic acid-to-quinolinic acid (KA/QA) ratio and hydroxykynurenine ratio (HKr) significantly mediated associations of carbohydrate, protein, fat, alcohol, magnesium, and zinc intake, and adherence to DHD recommendations, with physical and role functioning (ab). In conclusion, while all kynurenines simultaneously did not mediate diet-HRQoL associations, the KA/QA ratio and HKr did mediate several associations within the first year after CRC treatment.