Vitamin D and the endothelium: basic, translational and clinical research updates

Vitamin D deficiency has been associated with cardiovascular diseases (CVDs) and its surrogate indicators such as endothelial dysfunction. It is an independent predictor of CVDs and all-cause mortality. We review the updated literature surrounding vitamin D and the endothelium spanning molecular, translational and clinical studies including randomized controlled trials (RCTs). We review the possible actions of vitamin D on the quiescent and activated endothelium including lessons from animal models. We review the recent literature for association of Vitamin D deficiency with endothelial dysfunction and cardiovascular complications, and for clinical trials done to look at the effect of vitamin D supplementation on the endothelium and cardiovascular outcome. Vitamin D deficiency is associated with endothelial dysfunction and cardiovascular diseases. Vitamin D stabilizes the quiescent endothelium, modulates certain stages of endothelial activation, and is involved in the repair of the damaged endothelium in vitro and in vivo. Twelve recent cross sectional studies, including 2086 subjects of varying ethnic groups, show an association between endothelial dysfunction and vitamin D deficiency. Yet 10 recent RCTs of vitamin D supplementation involving 824 subjects have failed to show significant improvements in endothelial function in the short term. So far, RCTs have not been able to confirm or refute the benefit of vitamin D supplementation on vascular mortality. Longer term randomized controlled trials using doses of vitamin D to optimize serum 25(OH)D concentrations to 20.0–40.0 ng/mL (50.0–100.0 nmol/L) or using vitamin D analogues with no calciotropic effects are needed to assess endothelial function and cardiovascular outcomes.