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Am Fam Physician. 2019;100(6):374

Clinical Question

Does vitamin D supplementation prevent cardiovascular events or cancer in patients without known vascular disease or cancer?

Bottom Line

Vitamin D supplementation does not prevent cardiovascular events or cancer in mostly nondiabetic adults (men 50 years and older, women 55 years and older). (Level of Evidence = 1b)


Vitamin D deficiency is associated with many bad things including cancer, vascular disease, and dementia. This study is the first adequately powered U.S. trial of vitamin D supplementation for primary prevention of cardiovascular disease and cancer. It was designed as a factorial trial, with patients randomized to receive vitamin D 2,000 IU or placebo, and to receive marine n-3 fatty acids (also known as omega-3 fatty acids) or placebo. The marine n-3 fatty acid results are reported separately. The researchers recruited a total of 25,871 men 50 years and older, and women 55 years and older who had no history of cardiovascular disease or cancer. The groups were balanced at the start of the study, with a mean age of 67 years, 51% women, approximately 20% African Americans, and 14% with diabetes mellitus. Participants began with a three-month placebo run-in period to exclude those who were noncompliant (approximately one-third overall), which could overestimate the potential benefit seen in clinical practice. Of the participants, 12% had a vitamin D level less than 20 ng per mL (50 nmol per L) and 45% had a level less than 30 ng per mL (75 nmol per L). At the end of the median follow-up of 5.3 years, there was no difference in any of the trial end points (i.e., cardiovascular events, cardiovascular deaths, incident cancer, cancer deaths, or all-cause mortality). There was a small reduction in cancer deaths (112 vs. 149; hazard ratio = 0.75; 95% CI, 0.59 to 0.96), but that was only seen in the post hoc analysis that excluded events in the first two years with the rationale that any effect would take time to become apparent. Given the large number of comparisons made (19 in one table alone), this outcome could have occurred by chance. Results were similar for the subgroup of patients with lower vitamin D levels at baseline.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Population-based

Reference: Manson JE, Cook NR, LeeI M, et al.; VITAL Research Group. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33–44.

Editor's Note: Dr. Ebell is Deputy Editor for Evidence-Based Medicine for AFP and cofounder and Editor-in-Chief of Essential Evidence Plus, published by Wiley-Blackwell.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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