Effects of Heat Exposure on Kynurenine Pathway Metabolism—Comparison Between Exertional and Exogenous Heating of the Human Body

Background The kynurenine pathway (KP) plays a pivotal role in many diseases that involve distinct pathological mechanisms. Objectives Since KP metabolites are potential disease biomarkers, it is crucial to investigate their fluctuations under physiological conditions. As the KP is stress‐responsive, this study examines how peripheral KP metabolites change with core temperature increases induced by two different modalities. Methods In this randomized cross‐over study, 11 young healthy males were subjected to (a) exogenous heating via hot water immersion (44°C, EXO), and (b) exertional heating via exercise (EXE), until rectal temperature ( T rec ) reached 39°C, followed by a recovery phase. Blood samples were collected at baseline and at every 0.5°C T rec increment during both the heating and recovery phases. Plasma levels of KP metabolites, stress, and metabolic markers were measured. Correlation analyses between kynurenine pathway metabolites and stress markers were computed over the course of the trials. Results EXE and EXO trials induced the KP, but to different extents. Most plasma KP metabolite concentrations (kynurenic acid, picolinic acid, 3‐hydrokynurenine, quinolinic acid) increased. Stress markers were elevated in both trials. Changes in KP metabolites, stress, and metabolic markers were not persistent, and returned to baseline following recovery. Conclusion An elevation in body temperature by heat exposure or exercise increases peripheral concentration of several KP metabolites that return to baseline upon trial cessation, suggesting that KP enzymes are adaptable to physiological stressors.