The role of vitamin D in cardiovascular health

Vitamin D has multiple functions in most organs and tissues of the human body. In addition to its canonical role in bone and mineral metabolism, vitamin D impacts cell growth and differentiation, immunity, glucose homeostasis, cognition, and endocrine pathways. Mounting evidence links vitamin D deficiency to a broad spectrum of diseases including cardiovascular disease (CVD). Considering that both vitamin D deficiency and CVD are highly prevalent conditions, it is important to understand the potential interplay between these two. Observational studies consistently demonstrate an inverse relationship between the inactive prohormone 25-hydroxyvitamin D (25[OH]D) in serum, which represents the body's vitamin D reservoir, and CVD risk. Specifically, lower serum 25-(OH)D levels are associated with a higher risk of CVD events and CVD mortality. Putative mechanisms that mediate the pathophysiologic effects of vitamin D deficiency comprise oxidative stress, systemic inflammation, activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, hypertension, and myocardial fibrosis. However, vitamin D supplementation failed to demonstrate significant CVD-related benefits. Although existing randomized, placebo-controlled supplementation studies yielded neutral results, most of these studies did not specifically target CVD outcomes. Another limitation of previous randomized controlled studies is the application of fixed vitamin D dosing regimens, regardless of the actual serum 25-(OH)D level. Studies that escalate the vitamin D dose until serum 25-(OH)D reaches a prespecified target range are largely lacking. This article reviews the existing literature on the role of vitamin D deficiency in CVD incidence, progression, and mortality.