Influence of sex and time on cardiac remodeling induced by vitamin d supplementation

Abstract Background Vitamin D (VitD) exerts diverse biological effects, including on cardiac function, with a biphasic dose–response profile. The growing use of high-dose supplementation has raised concerns, as excessive VitD, even without hypercalcemia. However, the timing of these effects and the influence of biological sex remain unclear. This study evaluated whether excessive, non-hypercalcemic, VitD supplementation induces sex-specific alterations in components involved in myocardial inflammatory and oxidative stress pathways in rats, as well as to determine the temporal onset of these changes. Methods A total of 144 Wistar rats (72 males and 72 females) were assigned to control or VitD-supplemented groups for 20, 40, or 60 days. Supplemented animals received chow containing 10,000 IU/kg of cholecalciferol. Body weight, food intake, and cardiac compartment weights were recorded. Biochemical parameters and protein expression related to antioxidant, inflammatory, and apoptotic pathways were analyzed. Data were assessed using two-way ANOVA. Results VitD supplementation induced time and sex-dependent molecular changes. After 20 days, supplemented males showed increased glutathione peroxidase expression, indicating an early response. At 40 and 60 days, activation of the NF-κB inflammatory pathway was more pronounced, particularly in females. Heme oxygenase-1 expression exhibited temporal and sex-specific modulation. Conclusion Excessive non-hypercalcemic VitD supplementation promotes early and sex-specific alterations in myocardial antioxidant and inflammatory signalling pathways.