Vitamin D and Cardiovascular Health: A Systematic Review of Mechanisms, Epidemiological Evidence, and Randomized Controlled Trials

Abstract

Background: Vitamin D deficiency is widespread, affecting roughly one billion people worldwide. The discovery of vitamin D receptors in cardiac and vascular tissues has motivated extensive research into the relationship between vitamin D and cardiovascular health. Given the low cost and widespread availability of vitamin D supplements, establishing their cardiovascular effects has substantial public health implications. Objective: We conducted this systematic review to critically evaluate the mechanistic rationale, epidemiological evidence, and randomized controlled trial data examining the relationship between vitamin D and cardiovascular outcomes. We also aimed to translate these findings into practical clinical recommendations. Methods: This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We performed searches in PubMed, Scopus and Cochrane Library for clinical trials published in English language between January 2000 and January 30 2026. We included prospective studies, treatment randomized controlled trials with cardiovascular outcome data and meta-analyses. Methodological quality of the included studies was assessed using the Newcastle Ottawa scale for prospective cohort studies and Cochrane ROB 2 tool for treatment randomized controlled trials. Given the heterogeneity of the included trials, we performed a descriptive analysis of the results of the individual studies included in the meta-analysis. Results: Our search retrieved 847 records, of which 42 studies met our inclusion criteria. Preclinical evidence provides mechanistic plausibility for a cardioprotective effect, mediated through suppression of the renin-angiotensin-aldosterone system, improved vascular endothelial function, and reduced inflammation. Prospective observational studies consistently show that low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events. However, large randomized controlled trials have not demonstrated a corresponding benefit for major adverse cardiovascular events. The D-Health trial showed a reduction in major cardiovascular events (HR 0.91, 95% CI 0.81–1.01) and a significant reduction in myocardial infarction (HR 0.81, 95% CI 0.67–0.98), but no change in stroke incidence (HR 0.99, 95% CI 0.80–1.23). Meta-analyses of randomized controlled trials show no overall effect of vitamin D supplementation on major adverse cardiovascular events, stroke, or cardiovascular mortality. Conclusion: Current evidence from high-quality randomized trials does not support routine vitamin D supplementation for cardiovascular prevention in the general population. Supplementation remains appropriate for correcting deficiency for skeletal and other established indications. The possibility of benefit in severely deficient or highrisk subgroups requires further dedicated investigation.

Keywords: Vitamin D; 25Hydroxyvitamin D; Cardiovascular Disease; Systematic Review; Randomized Controlled Trials