The VITamin D and OmegA-3 TriaL (VITAL): Do Results Differ by Sex or Race/Ethnicity?

Abstract

Whether vitamin D or marine omega-3 (n-3) fatty acid supplementation reduces risk of cancer or cardiovascular disease (CVD) in general populations at usual risk for these outcomes is relatively unexplored in randomized trials. The primary goal of the VITamin D and OmegA-3 TriaL (VITAL), a nationwide, randomized, placebo-controlled, 2 × 2 factorial trial of vitamin D3 (2000 IU/day) and marine n-3 fatty acids (1 g/day) in the primary prevention of cancer and CVD among 25 871 US men aged ≥50 years and women aged ≥55 years, was to fill these knowledge gaps. Studying the influence of sex and race/ethnicity on treatment-related outcomes was a prespecified goal; such analyses help ensure that important effects are not missed and contribute to the foundation for developing targeted recommendations for supplement use. To enable investigation of potential sex- and race-specific treatment effects, trial investigators enrolled an even balance of men (n = 12 786) and women (n = 13 085) and oversampled African Americans (n = 5106). Significant or suggestive variation in intervention effects according to sex, race/ethnicity, and other participant characteristics was observed for some, though not all, outcomes. Additional research is needed to determine which individuals may be most likely to derive a net benefit from vitamin D or n-3 fatty acid supplementation. (VITAL clinicaltrials.gov identifier: NCT01169259).

Keywords: cancer; cardiovascular disease; marine n-3 fatty acids; primary prevention; race and ethnicity; randomized controlled trial; sex; vitamin D.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Shari S. Bassuk: VITAL receives grant support from the National Institutes of Health, which helps support my salary. Paulette D. Chandler: VITAL receives grant support from the National Institutes of Health, which helps support my salary. Julie E. Buring: VITAL receives grant support from the National Institutes of Health, which helps support my salary. Pharmavite LLC of Northridge, California (vitamin D) and Pronova BioPharma of Norway and BASF (Omacor fish oil) donated the study agents, matching placebos, and packaging in the form of calendar packs. My spouse serves on the Scientific Advisory Committee of Pharmavite. JoAnn E. Manson: VITAL receives grant support from the National Institutes of Health, which helps support my salary.

© 2020 The Author(s).

Figures

Figure 1.

VITAL Factorial Design. Adapted from Bassuk et al. with permission. Copyright ©2016, Elsevier.

Figure 2.

Cumulative incidence rate of cancer mortality by year of follow-up: vitamin D versus placebo. From Manson et al. with permission. Copyright ©2019, Massachusetts Medical Society.

Figure 3.

Cumulative incidence rates of major CVD events and total MI by year of follow-up, in the n-3 fatty acid group and the placebo group. Adapted from Manson et al. with permission. Copyright ©2019, Massachusetts Medical Society.

Figure 4.

Meta-analysis of randomized trials of vitamin D supplementation and cancer mortality. Source: From Keum et al. with permission. Copyright ©2019, Oxford University Press.

Figure 5.

Mechanisms by which vitamin D may lower cancer and cardiovascular disease risk. Adapted from Manson et al. with permission. Copyright ©2012, Elsevier.

Figure 6.

Mechanisms by which marine omega-3 fatty acids may lower cardiovascular disease risk. Adapted from Manson et al. with permission. Copyright ©2012, Elsevier.