Background Whether vitamin D supplementation reduces cancer or cardiovascular disease remains unclear, and randomized trial evidence is limited. Methods The VITamin D and OmegA-3 TriaL (VITAL) was a nationwide, randomized, placebo-controlled, 2X2 factorial trial of vitamin D3 (cholecalciferol, 2000 IU/day) and marine omega-3 fatty acids (1 g/day) for the prevention of cancer and cardiovascular disease. There were 25,871 U.S. men aged ≥50 and women aged ≥55, including 5,106 African Americans, who participated. Primary endpoints were total invasive cancer and major cardiovascular events (composite of myocardial infarction, stroke, and cardiovascular mortality). Secondary endpoints included site-specific cancers, cancer mortality, and additional cardiovascular events. Results Vitamin D supplementation did not reduce either of the primary endpoints. During a median 5.3 year intervention, 1,617 participants were diagnosed with cancer (793 assigned to vitamin D and 824 assigned placebo; hazard ratio [HR]=0.96; 95% confidence interval, 0.88–1.06; p-value=0.47); and 805 experienced a major cardiovascular event (396 assigned to vitamin D and 409 assigned to placebo; HR=0.97 [0.85–1.12]; p-value=0.69). For secondary endpoints, the hazard ratios and 95% confidence intervals comparing Vitamin D to placebo were: cancer deaths (n=341, HR 0.83 (0.67–1.02); breast cancer (1.02; 0.79–1.31); prostate cancer 0.88 (0.72–1.07); colorectal cancer 1.09 (0.73–1.62); expanded cardiovascular disease events 0.96 (0.86–1.08); myocardial infarction 0.96 (0.78–1.19); stroke 0.95 (0.76–1.20); and cardiovascular mortality 1.11 (0.88–1.40). The HR for all-cause deaths (n=978) was 0.99 (0.87–1.12). No excess risks of hypercalcemia or other adverse events were identified. Conclusion Vitamin D supplementation did not reduce invasive cancer incidence or cardiovascular events.

Background Whether omega-3 fatty acid supplementation reduces risk of cardiovascular disease or cancer remains unclear. Methods The VITamin D and OmegA-3Trial (VITAL) was a randomized, placebo-controlled, 2X2 factorial trial of vitamin D3 (2000IU/day) and marine omega-3 fatty acids (1 g/day) in the primary prevention of cardiovascular disease and cancer among 25,871 U.S. men aged ≥50 and women aged >55, including 5,106 African Americans. Primary endpoints were major cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality) and total invasive cancer. Secondary outcomes included individual components of the cardiovascular composite, the composite plus coronary revascularization, site-specific cancers, and cancer mortality. This paper reports the results of omega-3 and placebo. Results During a median 5.3 years, rates of the primary outcomes did not differ between the omega-3 and placebo groups -- 805 participants had a major cardiovascular event, hazard ratio [HR]= 0.92; 95% confidence interval [CI], 0.80–1.06, p= 0.24. Invasive cancer was diagnosed in 1,617 participants, HR 1.03 (0.93-1.13, p=0.56). In the analysis of key secondary endpoints, hazard ratios and 95% CIs comparing omega-3 to placebo were: expanded cardiovascular events, HR 0.93 (0.82-1.04); total myocardial infarction HR 0.72 (0.59-0.90); total stroke, HR 1.04 (0.83-1.31); cardiovascular mortality HR 0.96 (0.76-1.21); and cancer deaths (n=341, HR 0.97 (0.79-1.20). For all-cause mortality (n=978), the HR was 1.02 (0.90-1.15). No excess risks of bleeding or other serious adverse events were observed. Conclusions Omega-3 fatty acid supplementation did not reduce major cardiovascular events or cancer incidence.

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