Vitamin D Supplementation for Cardiovascular Disease Prevention—Reply

In Reply: Our Commentary critically appraised the evidence that vitamin D prevents cardiovascular disease and diabetes, highlighting that the available research is inconsistent and does not yet prove a cause-and-effect relationship. This is also the conclusion reached by the Agency for Healthcare Research and Quality,¹ the IOM,² and a meta-analysis of 51 trials.³ The meta-analysis, which documented the absence of supportive trial evidence, was cited by Holick et al⁴ in the Endocrine Society Clinical Practice Guideline, which stated: “We do not recommend prescribing vitamin D supplementation beyond recommended daily needs for the purpose of preventing cardiovascular disease or death or improving quality of life.” Thus, it is puzzling why Dr O’Keefe and colleagues now suggest that research demonstrates cardiovascular benefits of vitamin D. Association does not prove causation in observational studies, and confounding cannot be excluded as an explanation for correlations.² Large randomized trials designed to test hypotheses that benefits of high-dose vitamin D outweigh risks are important.