Vitamin D status modulates innate immune responses and metabolomic profiles following acute prolonged cycling

PURPOSE: The influence of vitamin D status on exercise-induced immune dysfunction remains unclear. The aim of this study was to investigate the effects of vitamin D status (circulating 25(OH)D) on innate immune responses and metabolomic profiles to prolonged exercise. METHODS: Twenty three healthy, recreationally active males (age 25 ± 7 years; maximal oxygen uptake [[Formula: see text] max] 56 ± 9 mL·kg(−1)·min(−1)), classified as being deficient (n = 7) or non-deficient n = 16) according to plasma concentrations of 25(OH)D, completed 2.5 h of cycling at 15% Δ (~ 55–60% [Formula: see text] max). Venous blood and unstimulated saliva samples were obtained before and after exercise. RESULTS: Participants with deficient plasma 25(OH)D on average had lower total lymphocyte count (mean difference [95% confidence interval], 0.5 cells × 10(9) L [0.1, 0.9]), p = 0.013) and greater neutrophil:lymphocyte ratio (1.3 cells × 10(9) L, [0.1, 2.5], p = 0.033). The deficient group experienced reductions from pre-exercise to 1 h post-exercise (− 43% [− 70, − 15], p = 0.003) in bacterial stimulated elastase in blood neutrophils compared to non-deficient participants (1% [− 20, 21], p = 1.000) Multivariate analyses of plasma metabolomic profiles showed a clear separation of participants according to vitamin D status. Prominent sources of variation between groups were purine/pyrimidine catabolites, inflammatory markers (linoleic acid pathway), lactate and tyrosine/adrenaline. CONCLUSION: These findings provide evidence of the influence of vitamin D status on exercise-induced changes in parameters of innate immune defence and metabolomic signatures such as markers of inflammation and metabolic stress. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-023-03181-1.