Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease

Randomized, placebo-controlled, 2-by-2 factorial trial in generally healthy older adults in the United States. Men were 50 years of age or older and women were 55 years of age or older, and all had no prior cancer except nonmelanoma skin cancer or cardiovascular disease at enrollment. Recruitment occurred nationwide from November 2011 through March 2014.

Participants received oral vitamin D3 (cholecalciferol) 2000 IU daily for the duration of the trial. The vitamin D regimen was tested in a 2-by-2 factorial design; one active arm also received marine n-3 fatty acids 1 g/day and the other received n-3 placebo.

Vitamin D3 did not reduce invasive cancer or major cardiovascular events over a median 5.3 years of follow-up. Invasive cancer was not significantly lower with vitamin D versus placebo (HR 0.96, 95% CI 0.88 to 1.06; P = 0.47), and major cardiovascular events were also not reduced (HR 0.97, 95% CI 0.85 to 1.12; P = 0.69). Cancer death (HR 0.83, 95% CI 0.67 to 1.02), deaths from any cause (HR 0.99, 95% CI 0.87 to 1.12), and major cardiovascular endpoints including myocardial infarction, stroke, and cardiovascular death were likewise not significantly different. No excess hypercalcemia or other adverse events attributable to vitamin D were identified.

Follow-up was moderate at 5.3 years, which may be insufficient for some cancer outcomes. Participants were generally healthy older adults and were not selected for vitamin D deficiency; mean baseline 25-hydroxyvitamin D was 30.8±10.0 ng/mL, so results may not generalize to deficient populations. Arm-specific age and BMI data were not reported, and baseline out-of-trial vitamin D use was allowed up to 800 IU/day, which may have narrowed the exposure contrast.