Background: It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease, and data from randomized trials are limited.
Methods: We conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (cholecalciferol) at a dose of 2000 IU per day and marine n-3 (also called omega-3) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes). Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. This article reports the results of the comparison of vitamin D with placebo.
Results: A total of 25,871 participants, including 5106 black participants, underwent randomization. Supplementation with vitamin D was not associated with a lower risk of either of the primary end points. During a median follow-up of 5.3 years, cancer was diagnosed in 1617 participants (793 in the vitamin D group and 824 in the placebo group; hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47). A major cardiovascular event occurred in 805 participants (396 in the vitamin D group and 409 in the placebo group; hazard ratio, 0.97; 95% CI, 0.85 to 1.12; P=0.69). In the analyses of secondary end points, the hazard ratios were as follows: for death from cancer (341 deaths), 0.83 (95% CI, 0.67 to 1.02); for breast cancer, 1.02 (95% CI, 0.79 to 1.31); for prostate cancer, 0.88 (95% CI, 0.72 to 1.07); for colorectal cancer, 1.09 (95% CI, 0.73 to 1.62); for the expanded composite end point of major cardiovascular events plus coronary revascularization, 0.96 (95% CI, 0.86 to 1.08); for myocardial infarction, 0.96 (95% CI, 0.78 to 1.19); for stroke, 0.95 (95% CI, 0.76 to 1.20); and for death from cardiovascular causes, 1.11 (95% CI, 0.88 to 1.40). In the analysis of death from any cause (978 deaths), the hazard ratio was 0.99 (95% CI, 0.87 to 1.12). No excess risks of hypercalcemia or other adverse events were identified.
Conclusions: Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259 .).