Vitamin D is not effective as primary prevention of cardiovascular disease or cancer (VITAL)

Reference

Manson JE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cardiovascular disease and cancer. N Engl J Med 2019;380(1):33-44.

Synopsis

Vitamin D deficiency is associated with many bad things including cancer, vascular disease, and dementia. This study is the first adequately powered US trial of vitamin D supplementation for primary prevention. It was designed as a factorial trial, with patients randomized to receive vitamin D 2000 IU or placebo, and to receive marine n-3 fatty acids (also known as omega-3 fatty acids) or placebo. The 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. Participants began with a 3-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/mL (50 nmol/L) and 45% had a level less than 30 ng/mL (75 nmol/L). At the end of the median follow-up of 5.3 years, there was no difference in any the trial endpoints (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 - 0.96), but that was only seen in the post hoc analysis that excluded events in the first 2 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 easily have occurred by chance. Results were similar for the subgroup of patients with lower vitamin D levels at baseline.