Vitamin D and Atherosclerotic Cardiovascular Disease

Abstract

Context A large body of experimental and observational data has implicated vitamin D deficiency in the development of cardiovascular disease. However, evidence to support routine vitamin D supplementation to prevent or treat cardiovascular disease is lacking. Design and Results A comprehensive literature review was performed using PubMed and other literature search engines. Mounting epidemiological evidence and data from Mendelian randomization studies support a link between vitamin D deficiency and adverse cardiovascular health outcomes, but randomized trial evidence to support vitamin D supplementation is sparse. Current public health guidelines restrict vitamin D intake recommendations to the maintenance of bone health and prevention of fractures. Two recently published large trials (VITAL and ViDA) that assessed the role of moderate- to high-dose vitamin D supplementation as primary prevention for cardiovascular outcomes in the general population had null results, and previous randomized trials have also been generally negative. These findings from general population cohorts that are largely replete in vitamin D may not be applicable to chronic kidney disease (CKD) populations, in which the use of active (1α-hydroxylated) vitamin D compounds is prevalent, or to other high-risk populations. Additionally, recent trials in the CKD population, as well as trials using vitamin D analogs, have been limited. Conclusions Current randomized trials of vitamin D supplementation do not support benefits for cardiovascular health, but the evidence remains inconclusive. Additional randomized trials assessing larger numbers of participants with low baseline vitamin D levels, having longer follow-up periods, and testing higher vitamin D dosages are needed to guide clinical practice.

Vitamin D Deficiency and the Risk of Cerebrovascular Disease

“…Such controversy is akin to that regarding the putative beneficial effects of antioxidants in optimizing health [200], with the reported discrepancies likely due to the complexity of the systems and existence of multiple confounding factors. Indeed, a careful analysis of existing RTC and related meta-analysis studies on the effects of vitamin D supplementation reveals several methodological limitations, including the use of diverse study populations, different doses of vitamin D with or without Ca 2+ , different durations of supplementation and follow-up, different baseline and acquired circulating 25(OH)D concentrations, and different study outcome parameters [99,201]. Furthermore, significant discrepancies could result from the large inter-individual variation in genetic determinants of the efficacy of vitamin D supplementation [12,109,110], as well as its context-dependent effects on mechanisms in endothelial cells, including autophagy [202].…”

Vitamin D Toxicity

“…In fact, mounting experimental, observational, and epidemiologic evidence has linked low vitamin D levels to a number of adverse health outcomes, such as all-cause mortality, cardiovascular disease, reduced bone density, fracture risk, metabolic syndrome, malignancy, autoimmune conditions, and infection. 2 Additionally, some evidence suggests that vitamin D status is a biomarker of lifestyle, given that unhealthy and sedentary lifestyles are associated with vitamin D insufficiency or deficiency, which itself represents a risk factor for adverse health outcomes. 3 Lack of adequate sunlight exposure, skin color, and socio-religious practices are all contributors to vitamin D insufficiency or deficiency.…”

“…The reader is referred elsewhere for a discussion on vitamin D physiology, metabolism, and current randomized trial data. 2 …”

The unsettled science of nonrenal calcitriol production and its clinical relevance

“…Commentary on the details of these trials, most of which showed no effect, has been extensive and will not be considered here (10); three recent trials, however, merit reference. The recently concluded VITAL trial (VITamin D and OmegA-3 TriaL), aimed at assessing the ability of supplemental vitamin D to prevent cancer and cardiovascular disease, resulted in the general absence of an impact of the vitamin on either of these diseases, although a modest potential effect on cancer was noted upon careful secondary evaluation (10,11). A second trial conducted to determine the impact of high-dose supplemental vitamin D on prediabetic progression did not reach statistical significance (12).…”