Background: Exercise elicits systemic adaptations through a coordinated network of exercise-responsive signaling molecules termed exerkines. Vitamin D, classically linked to calcium homeostasis, has been increasingly characterized as a pleiotropic hormone with immunomodulatory and myotropic actions that may be relevant to training adaptation and recovery in athletic populations.
Objective: This narrative review synthesizes mechanistic and clinical evidence examining whether vitamin D status and supplementation are associated with modulation of selected exercise-responsive exerkines, and it introduces a unifying conceptual model, the "vitamin D-exerkine axis", to frame potential points of interaction between vitamin D signaling and the exercise-induced secretome.
Methods: A narrative literature review was conducted using searches of PubMed and Google Scholar, incorporating mechanistic, observational, and intervention studies in animal and human models relevant to vitamin D signaling and exercise-responsive exerkines. Evidence was synthesized qualitatively to distinguish biological plausibility from athlete-specific causal inference.
Results: Across experimental systems, vitamin D signaling via the vitamin D receptor (VDR) has been associated with expression of several exerkines implicated in inflammation, metabolism, and muscle remodeling. Evidence most consistently discussed in the literature involves IL-6, irisin/FNDC5, myostatin, and anti-inflammatory cytokines (e.g. IL-10), although effect direction and magnitude appear context-dependent and are influenced by baseline vitamin D status, study design, and outcome timing. A bidirectional relationship is plausible: exercise may upregulate VDR expression in skeletal muscle and has been associated with transient changes in circulating vitamin D metabolites, while vitamin D sufficiency may shape aspects of the post-exercise inflammatory and metabolic milieu. Collectively, these observations support a working model in which vitamin D status could modulate parts of the exercise-response signaling network, but definitive athlete-focused causal evidence remains limited.
Conclusion: The proposed vitamin D-exerkine axis offers a hypothesis-generating conceptual model for integrating nutrition endocrinology with exercise physiology. Current data support biological plausibility for interaction, yet heterogeneity in study populations, endpoints, and supplementation protocols constrains strong causal inference in athletes. Future research should prioritize well-controlled trials that account for baseline 25(OH)D status, define dose-response relationships, test sex- and sport-specific effects, and incorporate tissue-level endpoints to clarify mechanisms and relevance to training adaptation and recovery.
Keywords: Vitamin D; exercise adaptation; exerkines; myokines; vitamin D receptor (VDR).