Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 134000 Individuals in 29 Randomized Clinical Trials and 157000 Individuals in 30 Prospective Cohort Studies: An Updated Systematic Review and Meta-analysis

Background: According to the findings from observational studies and clinical trials assessing the effect of vitamin D supplements on cardiovascular diseases (CVDs), there are still contradictory results. This systematic review aimed to assess the effect of vitamin D supplements on CVDs considering cohort studies and clinical trials. Study Design: A systematic review. Methods: MEDLINE/PubMed, Science Direct, Embase, and Cochrane Library databases were reviewed by two reviewers independently until 2022. The study effect is risk ratio (RR) and 95% confidence interval (CI) according to Mantel Haenszel’s random-effects model. Then, Stata version 14 was used for statistical analysis. Results: In clinical trial studies, the incidence of CVDs among the vitamin D-consuming group was not significantly different from that in the placebo group (RR: 0.99, 95% CI: 0.95-1.03; P=0.77; I 2=0%). CVD mortality was also not significantly different between the two groups (RR: 0.97, 95% CI: 0.90-1.05; P=0.72; I2=0%). In cohort studies, circulating 25 (OH) D increased the risk of CVD incidence by 31% (RR: 1.31, 95% CI: 1.19-1.45) and CVD mortality by 37% (RR: 1.37, 95% CI: 1.17-1.61). Conclusion: According to current evidence from clinical trials, vitamin D supplementation should not be recommended for CVD prevention. However, there is a direct association between vitamin D deficiency and the incidence of CVDs as well as its mortality. According to the results of clinical trial studies carrying higher levels of scientific evidence, it can be concluded that vitamin D supplementation does not exert a significant effect on the incidence, mortality, and reduction of CVDs.