Abstract
The role of vitamin D in reducing cardiovascular disease (CVD) risk remains debated despite growing evidence. Prospective observational studies consistently show that low serum 25-hydroxyvitamin D [25(OH)D] concentrations (below 40-50 nmol/L [16-20 ng/mL]) are associated with the highest risk of CVD incidence. In addition, a large prospective observational study found that serum 25(OH)D concentration was inversely correlated with CVD mortality rate to over 100 nmol/L. Randomized controlled trials have not generally demonstrated benefit due to faulty study designs, such as enrolling participants with baseline 25(OH)D levels > 50 nmol/L. However, a major trial found that 60,000 IU/month of vitamin D(3) supplementation reduced the risk of major cardiovascular events for participants with predicted 25(OH)D concentrations ≥ 50 nmol/L or taking statins or CV drugs by ~13 to ~17%. In addition, vitamin D supplementation studies have found modest reductions in several CVD risk factors. Other observational studies of vitamin D supplementation have reported reduced CVD risks (e.g., ischemic heart disease, hypertension, and myocardial infarction). Temporal ecological studies further support this relationship, revealing that CVD incidence rates are lowest in summer and CVD mortality rates are significantly higher in late winter-when 25(OH)D concentrations are lowest-compared to late summer. A previously reported analysis using eight of Hill's criteria for causality in a biological system further strengthens the biological plausibility of vitamin D's role in CVD risk reduction. Its role in modulating inflammation and oxidative stress, improving endothelial function, and reducing several cardiometabolic risk factors supports its inclusion as part of a comprehensive, multi-modal approach to cardiovascular health. Therefore, vitamin D should be considered an integral component in the prevention and management of CVD. Preferably, it should be used in combination with other nutritional supplements, a heart-healthy diet, and prescription medications to reduce the risk of CVD incidence. People should consider vitamin D(3) supplementation with at least 2000 IU/day (50 mcg/day) (more for those who are obese) when sun exposure is insufficient to maintain serum 25(OH)D concentrations above 75 nmol/L. To reduce CVD mortality rates, higher doses to achieve higher 25(OH)D concentrations might be warranted.