Principal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyses of relevant vitamin D trials
JoAnn E. Manson The Journal of Steroid Biochemistry and Molecular Biology Volume 198, April 2020,
Highlights
• In VITAL, vitamin D did not reduce the primary cancer or cardiovascular endpoints.
• Vitamin D reduced total cancer mortality in analyses excluding early follow up.
• Meta-analyses of trials show a reduction in cancer mortality but not incidence.
• More research is needed to identify those most likely to benefit from vitamin D.
Whether supplemental vitamin D reduces risk of cancer or cardiovascular disease (CVD) is relatively unexplored in randomized trial settings. The VITamin D and OmegA-3 TriaL (VITAL) was a nationwide, randomized, placebo-controlled, 2 × 2 factorial trial of daily vitamin D3 (2000 IU) and marine omega-3 fatty acids (1 g) in the primary prevention of cancer and CVD among 25,871 U.S. men aged ≥50 and women aged ≥55, including 5106 African Americans. Median treatment duration was 5.3 years. Vitamin D did not significantly reduce the primary endpoint of total invasive cancer incidence (hazard ratio [HR] = 0.96 [95% confidence interval 0.88–1.06]) but showed a promising signal for reduction in total cancer mortality (HR = 0.83 [0.67–1.02]), especially in analyses that accounted for latency by excluding the first year (HR = 0.79 [0.63–0.99]) or first 2 years (HR = 0.75 [0.59–0.96]) of follow-up.
Vitamin D did not significantly reduce the co-primary endpoint of major CVD events (HR = 0.97 [0.85–1.12]), other cardiovascular endpoints, or all-cause mortality (HR = 0.99 [0.87–1.12]). Updated meta-analyses that include VITAL and other recent vitamin D trials indicate a significant reduction in cancer mortality but not in cancer incidence or CVD endpoints. Additional research is needed to determine which individuals may be most likely to derive a net benefit from vitamin D supplementation.