Principal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyses of relevant vitamin D trials

Abstract

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. (VITAL clinicaltrials.gov identifier: NCT01169259).

Keywords: Cancer; Cardiovascular disease; Primary prevention; Race and ethnicity; Randomized controlled trial; Vitamin D.

Conflict of interest statement

Declaration of Competing Interest All authors have submitted a completed ICMJE (International Committee of Medical Journal Editors) for Disclosures of Potential Conflicts of Interest.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Figures

Figure 1.. VITAL Factorial Design

Adapted from Bassuk SS et al., Contemp Clin Trials 2016; 47:235-243

Figure 2.

Cumulative Incidence Rates of Cancer Mortality by Year of Follow-up: Vitamin D vs. Placebo Source: Manson JE et al., N Engl J Med 2019;380:33-44.

Figure 3.

Meta-analysis of randomized trials of vitamin D supplementation and cancer mortality (Keum et al., Ann Oncol 2019; 30(5):733-743.).

Figure 4.. Mechanisms by which Vitamin D May Lower Cancer and Cardiovascular Disease Risk

Adapted from: Manson JE et al., Contemp Clin Trials 2012; 33:159-171.