Vitamin D and cardiovascular disease: an appraisal of the evidence.

Supplementation with vitamin D has received attention as a potential cardioprotective strategy. Biologically plausible mechanisms have been proposed to link vitamin D to coronary heart disease (CHD) prevention, and observational studies suggest an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and CHD. Few randomized clinical trials of vitamin D supplementation and CHD have been conducted, however, and no trial with CHD as the primary prespecified outcome has been completed. A search was conducted in PubMed to find prospective studies of the use of vitamin D supplementation and its relationship to cardiovascular risk factors (RFs) and/or cardiovascular disease (CVD). The exact search query was: ((vitamin D supplement*[Title/Abstract]) AND cardiovascular [Title/Abstract]) AND prospective [Title/Abstract]. This query yielded 42 results. "Randomized Controlled Trial" (article type) was used as a filter in a subsequent query with the same search terms. We review the evidence that vitamin D supplementation modifies coronary RFs, such as blood pressure, lipids, glucose tolerance, and/or affects the development of clinical CHD events. We address potential sources of confounding in observational epidemiologic studies of the relationship between serum 25OHD and CHD. We also address laboratory assay issues relevant to the reliable measurement of 25OHD. Most vitamin D supplementation trials have not demonstrated improvement in CVD, but they have tested relatively low vitamin D doses. Thus, the evidence remains inconclusive, highlighting the need for rigorous randomized trials of higher vitamin D doses with cardiovascular events as prespecified outcomes. While we await the results of ongoing trials, the recommended dietary allowances from the Institute of Medicine remain the best guidepost for nutritional requirements.