Vitamin D and Cardiovascular Disease, with Emphasis on Hypertension, Atherosclerosis, and Heart Failure

Abstract

Vitamin D deficiency is the most common nutritional deficiency, affecting almost one billion people worldwide. Vitamin D is mostly known for its role in intestinal calcium absorption and bone mineralization. However, the observation of seasonal changes in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in cardiomyocytes, as well as endothelial and vascular smooth muscle cells, implicated a role of vitamin D in the cardiovascular system. Animal studies provided compelling evidence that vitamin D signaling is essential for cardiovascular integrity, especially for the regulation of vascular tone and as an antifibrotic and antihypertrophic signaling pathway in the heart. In addition, observational studies reported an association between vitamin D deficiency and risk of hypertension, atherosclerosis, and heart failure. However, recent clinical intervention studies failed to prove the causal relationship between vitamin D supplementation and beneficial effects on cardiovascular health. In this review, we aim to highlight our current understanding of the role of vitamin D in the cardiovascular system and to find potential explanations for the large discrepancies between the outcome of experimental studies and clinical intervention trials.

Vitamin D and Cardiovascular Disease: An Updated Narrative Review

“…Binding of 1,25(OH) 2 D induces a conformational change in the vitamin D receptor (VDR), leading to hetero-dimerization with the retinoid X receptor and ultimately to translocation of this complex into the nucleus, where it binds to vitamin D response elements in the promoter region of target genes. A variety of extra-renal cells also exhibit 1α-hydroxylase activity, indicating that in these cells the biological effects are determined by the sum of circulating and locally produced 1,25(OH) 2 D [ 14 ].…”

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions

“…Considering that numerous clinical studies have reported that vitamin D supplementation mitigates cardiovascular disease [158,159], it is worth mentioning that over the years various groups have observed a link between vitamin D and irisin expression. In diabetic animal models, vitamin D increases irisin expression [160].…”

Vitamin D Deficiency and Risk of Metabolic Syndrome in Aging Men

“…Vitamin D has been implicated in the regulation of several pathways, besides its well-known role as regulator of the calcium-phosphate metabolism, it has been suggested that it may be implicated in immune system modulation [ 29 ], in the regulation of muscle strength and metabolism and in the cognitive decline [ 51 ]. Moreover, hypovitaminosis D has been considered risk factors for CVD [ 52 ]. Both cross-sectional [ 53 54 55 ] and longitudinal studies [ 56 ] suggested a role for hypovitaminosis D in predicting the development of cardio metabolic risk factors as MetS and diabetes.…”