Vitamin D is known to elicit a vasoprotective effect, while vitamin D deficiency is a risk factor for endothelial dysfunction (ED). ED is characterized by reduced bioavailability of a potent endothelium-dependent vasodilator, nitric oxide (NO), and is an early event in the development of atherosclerosis. In endothelial cells, vitamin D regulates NO synthesis by mediating the activity of the endothelial NO synthase (eNOS). Under pathogenic conditions, the oxidative stress caused by excessive production of reactive oxygen species (ROS) facilitates NO degradation and suppresses NO synthesis, consequently reducing NO bioavailability. Vitamin D, however, counteracts the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which produces ROS, and improves antioxidant capacity by enhancing the activity of antioxidative enzymes such as superoxide dismutase. In addition to ROS, proinflammatory mediators such as TNF-α and IL-6 are risk factors for ED, restraining NO and eNOS bioactivity and upregulating the expression of various atherosclerotic factors through the NF-κB pathway. These proinflammatory activities are inhibited by vitamin D by suppressing NF-κB signaling and production of proinflammatory cytokines. In this review, we discuss the diverse activities of vitamin D in regulating NO bioavailability and endothelial function.

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

Creatine is a naturally occurring compound, functioning in conjunction with creatine kinase to play a quintessential role in both cellular energy provision and intracellular energy shuttling. An extensive body of literature solidifies the plethora of ergogenic benefits gained following dietary creatine supplementation; however, recent findings have further indicated a potential therapeutic role for creatine in several pathologies such as myopathies, neurodegenerative disorders, metabolic disturbances, chronic kidney disease and inflammatory diseases. Furthermore, creatine has been found to exhibit non-energy-related properties, such as serving as a potential antioxidant and anti-inflammatory. Despite the therapeutic success of creatine supplementation in varying clinical populations, there is scarce information regarding the potential application of creatine for combatting the current leading cause of mortality, cardiovascular disease (CVD). Taking into consideration the broad ergogenic and non-energy-related actions of creatine, we hypothesize that creatine supplementation may be a potential therapeutic strategy for improving vascular health in at-risk populations such as older adults or those with CVD. With an extensive literature search, we have found only four clinical studies that have investigated the direct effect of creatine on vascular health and function. In this review, we aim to give a short background on the pleiotropic applications of creatine, and to then summarize the current literature surrounding creatine and vascular health. Furthermore, we discuss the varying mechanisms by which creatine could benefit vascular health and function, such as the impact of creatine supplementation upon inflammation and oxidative stress.

Purpose: The primary aim of this study was to determine the efficacy of acute fish oil (FO) supplementation on indices of exercise-induced muscle damage (EIMD) in young healthy adults. Methods: Twenty-two healthy young male and females were randomly assigned to two experimental groups: fish oil (FO) or placebo control (CON). Participants performed a muscle damage protocol consisting of 10 sets of 10 plyometric drop jumps. Vertical jump height, isometric maximal voluntary contraction (MVC) torque, and systemic inflammation markers were assessed at pre-exercise, immediately post (post-0), post-24, post-48, and post-72 h. Results: Vertical jump performance and quadriceps peak torque significantly decreased in the CON group at post-0, 24, and 48 h (p < 0.05), while FO group recovered to baseline levels by post 48 h. Hamstring peak torque reductions recovered in the FO group at post-48 h but remained suppressed in the CON group until post-72 h (p < 0.05). Muscle soreness was significantly higher in the CON group compared to the FO group at post-48 h (p < 0.05). Systemic TNF-α levels significantly increased from baseline to post-0, 24, and 48 h in both groups (p < 0.05), with the CON group showing a trend toward incomplete recovery (p = 0.065). Conclusions: Our findings indicate that acute FO administration may modestly aid muscle recovery and reduce muscle soreness following EIMD in healthy young adults while the overall impact may be limited.

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. 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. 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. 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. 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.