Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease

Trial Reference

Manson JE, Cook NR, Lee IM, Christen W, VITAL Research Group. Vitamin D supplements and prevention of cancer and cardiovascular disease (VITAL). N Engl J Med. 2019 Jan 3;380(1):33-44.

Abstract | Full Text


Expert Comment

Ricardo Lopez Santi, ISCP Governor for Argentina



During the last 20 years we have obtained more doubts regarding the benefits of some supplements, which are usually available in food, in the cardiovascular prevention field. Sometimes the data was gathered from observational studies, others times from pos hoc analysis or over small populations, but the final conclusions were always weak. In this way vitamin D and Omega 3 fatty acids have stimulated some hypotheses as prevention tools of non-communicable diseases, such as cardiovascular disease and cancer.

Recently the New England Journal of Medicine published two articles from the VITAL Research group with the support of the US National Institutes of Health (NIH). Probably it is the most important interventional trial on both kinds of supplements strengthened by a large study population, a high dose of vitamin D, the profile of recruitment patients and the appropriate time of follow-up.

This study was a nationwide, randomized and placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (cholecalciferol) at a dose of 2000 IU per day, omega-3 fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the US. Eligible participants were in primary prevention condition, had no history of cancer or cardiovascular disease at trial entry, and they were required to agree to limit the use of vitamin D from all supplemental sources, including multivitamins, to 800 IU per day and to complete a 3-month placebo run-in phase.

A total of 25,871 participants, including 5,106 black participants, underwent randomization. The results shows that the supplementation with vitamin D was not associated with a lower risk of either of the primary end points. During a median follow-up of 5.3 years, cancer was diagnosed in 1617 participants (793 in the vitamin D group and 824 in the placebo group; hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47). A major cardiovascular event occurred in 805 participants (396 in the vitamin D group and 409 in the placebo group; hazard ratio, 0.97; 95% CI, 0.85 to 1.12; P=0.69).


The conclusions are clear, there is no doubt about the lack of benefits throughout more than 5 years of follow-up. The results of subgroup analyses show the reduction of cancer risk in African American participants and the possibility of differential effects on cancer incidence according to body mass index, with normal-weight participants having a lower incidence than those who received placebo. However, no benefits were recorded regarding cardiovascular disease.

Perhaps these observations carry on to new hypotheses. Some limitations of this study were that the population was chosen according to specific design for the US, that it dispensed only one dose of vitamin D and that 43% of participants were already taking a vitamin D supplement at the start of the trial. For this reason, it would be interesting to analyze what would happen in others regions with different doses and in a population that previously receives a low level of vitamin D, but probably the results would be similar.

After the results of lack of benefits, the obvious question appears: is this the end of the way? The outcomes of this study lead us to think the answer is yes. But it is only my own perspective. What do you think about this?

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