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

J Steroid Biochem Mol Biol. 2020 Apr:198:105522. doi: 10.1016/j.jsbmb.2019.105522. Epub 2019 Nov 13.


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 identifier: NCT01169259).

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

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cholecalciferol / therapeutic use*
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / epidemiology
  • Neoplasms / prevention & control*
  • Placebo Effect
  • Vitamins / therapeutic use*


  • Fatty Acids, Omega-3
  • Vitamins
  • Cholecalciferol

Associated data