Vitamin D is a precursor of the steroid hormone calcitriol that is crucial for bone and mineral metabolism. Both the high prevalence of vitamin D deficiency in the general population and the identification of the vitamin D receptor in the heart and blood vessels raised interest in the potential cardiovascular effects of vitamin D. Experimental studies have demonstrated various cardiovascular protective actions of vitamin D, but vitamin D intoxication in animals is known to induce vascular calcification. In meta-analyses of epidemiological studies, vitamin D deficiency is associated with an increased cardiovascular risk. Findings from Mendelian randomization studies and randomized, controlled trials (RCTs) do not indicate significant effects of a general vitamin D supplementation on cardiovascular outcomes. Previous RCTs, however, were not adequately designed to address extra skeletal events, and did not focus on vitamin D-deficient individuals. Therefore, currently available evidence does not support cardiovascular benefits or harms of vitamin D supplementation with the commonly used doses, and whether vitamin D has cardiovascular effects in individuals with overt vitamin D deficiency remains to be evaluated. Here, we provide an update on clinical studies on vitamin D and cardiovascular risk, discuss ongoing vitamin D research, and consider the management of vitamin D deficiency from a cardiovascular health perspective.
Key points
- The vitamin D receptor (VDR) and enzymes for vitamin D metabolism are expressed throughout the cardiovascular system
- VDR and 1α-hydroxylase knockout mice have hypertension with myocardial hypertrophy and increased activity of the renin–angiotensin–aldosterone system
- The molecular effects of VDR activation indicate various anti-atherosclerotic and protective effects on the heart and on common cardiovascular risk factors
- Observational studies have shown that low 25-hydroxyvitamin D levels are associated with an adverse cardiovascular risk profile and significantly increased risk of cardiovascular events
- Mendelian randomization studies and randomized clinical trials have not shown significant effects of vitamin D on cardiovascular events, but these trials were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals
- Vitamin D supplementation is currently not indicated for the purpose of cardiovascular disease prevention, but treatment of vitamin D deficiency is critical for skeletal health
Introduction
The critical involvement of vitamin D in bone and mineral metabolism is historically known. The identification of the vitamin D receptor (VDR) in almost all human organs including the heart and the blood vessels, and observations that individuals deficient in vitamin D are at increased risk of various extraskeletal diseases, stimulated research on the role of vitamin D for overall and cardiovascular health. In this Review, we summarize the existing knowledge on the effects of vitamin D on cardiovascular diseases and associated risk factors, with a particular focus on meta-analyses of large, epidemiological studies and randomized, controlled trials (RCTs). First, we provide a short summary of vitamin D metabolism and current vitamin D guidelines, a historical perspective on vitamin D and cardiovascular diseases, and a brief overview on the mechanistic effects of VDR activation on cardiovascular risk factors, the blood vessels, and the heart. The principal aspect of this Review is an update on observational studies, Mendelian randomization studies, and RCTs on vitamin D and cardiovascular risk. Finally, we outline and discuss ongoing vitamin D research, including large RCTs, and present our conclusions on how to deal with the management of vitamin D deficiency from a public health and cardiovascular health perspective.
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| Figure 1: Human metabolism of vitamin D. |
Vitamin D and cardiovascular disease prevention
