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

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Manson, JoAnn E., Bassuk, Shari S., Buring, Julie E.·2020·The Journal of Steroid Biochemistry and Molecular Biology
DOI 10.1016/j.jsbmb.2019.105522PMC PMC7089819
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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 D 3 (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).

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  • The VITAL study, which included more than 25,000 healthy individuals, failed to show significant reductions in major cardiovascular events with EPA + DHA supplementation.

    “Similarly, both the ASCEND trial [90], conducted in 15,480 diabetic patients without known cardiovascular disease, and the VITAL study [91], which included > 25,000 healthy individuals, failed to show significant reductions in major cardiovascular events with EPA + DHA supplementation.”

    From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [91]

    The VITAL Overview (Design; page unavailable) confirms that 25,871 participants were randomized to receive, among other treatments, an EPA+DHA supplement. The VITAL Results and Conclusion (pages unavailable) report no significant reduction in major cardiovascular events for vitamin D, but the passages found do not report that outcome for EPA+DHA. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The VITAL trial noted a modest reduction in myocardial infarction, but overall cardiovascular risk was unaffected.

    “Although results from the VITAL trial noted a modest reduction in myocardial infarction, the overall cardiovascular risk was unaffected [91].”

    From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [91]

    The ‘Vitamin D and Cardiovascular Disease—VITAL results’ section reports no reduction in major cardiovascular events, supporting the overall-risk portion of the claim. It also says vitamin D did not reduce myocardial infarction (HR 0.96, 95% CI 0.78–1.19), so the claim’s suggestion of a myocardial-infarction benefit is not supported by the results reported here. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Manson, J. E., Bassuk, S. S., & Buring, J. E.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Manson, JoAnn E.
ORCID
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2020-04
Volume
198
Pages
105522
ISSN
0960-0760 (ISSN-L)
DOI
10.1016/j.jsbmb.2019.105522
PMC
PMC7089819
OpenAlex
W2989138264
Cited by
161
References
94
Citations by year
2026: 29 · 2025: 29 · 2024: 32 · 2023: 32 · 2022: 19 · 2021: 10 · 2020: 10
FWCI
7.18
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
vitamin D supplementation, vitamin D3, omega-3 fatty acids, marine fatty acids, cancer incidence, cancer mortality, cardiovascular disease, major adverse cardiovascular events, all-cause mortality, primary prevention, older adults, African Americans, VITAL trial
MeSH terms
Aged, Cardiovascular Diseases, Cholecalciferol, Female, Humans, Male, Middle Aged, Neoplasms, Vitamins, Fatty Acids, Omega-3, Placebo Effect

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