VITAL trial on vitamin D

VITAL trial on vitamin D

Role of vitamin D in cardiovascular disease has been suggested by observational studies. Low blood levels of vitamin D was found to be associated with higher risks of heart disease, stroke, hypertension and diabetes mellitus [1]. But the 2011 Institute of Medicine (United States) guidance concluded that the evidence is inconsistent and inconclusive, not meeting the criteria for a cause effect relationship [2].

VITAL study was a randomized placebo controlled trial of vitamin D3 (cholecalciferol) at a dose of 2000 IU per day and omega-3 fatty acids at a dose of 1 g per day for prevention of cancer and cardiovascular disease [3]. 25,871 participants were men aged 50 years or more and women aged 55 years or more in the United States. Primary end points of the study were invasive cancer of any type and major cardiovascular events which was a composite of myocardial infarction, stroke or death from cardiovascular causes. Secondary endpoints were site specific cancer, death from cancer and additional cardiovascular events. Median follow up period of the VITAL study was 5.3 years.

396 major cardiovascular events occurred in the vitamin D group and 409 in the placebo group. The difference was not statistically significant. Vitamin D supplementation did not result in lower incidence of invasive cancer. There was no excess risks of hypercalcemia or other adverse events due to vitamin D supplementation in the study [3]. No significant differences in the secondary cardiovascular end points or all cause mortality was documented.

The Vitamin D Assessment Study (ViDA) from New Zealand reported on 5108 participants given an oral vitamin D3 dose of 200,000 IU followed by monthly doses of 100,000 IU or placebo [4]. The median follow up period was 3.3 years. ViDA study concluded that monthly high dose vitamin D supplementation did not prevent cardiovascular disease.

Two year post intervention follow up of VITAL study is looking for latency effects and possible increase in statistical power to assess end points. It was thought that detection of a decrease in death rate from any cause may need a longer follow up. The study was funded by the National Institutes of Health of the United States.

References

1. Danik JS, Manson JE. Vitamin d and cardiovascular disease. Curr Treat Options Cardiovasc Med. 2012 Aug;14(4):414-24.
2. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan;96(1):53-8.
3. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D’Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019 Jan 3;380(1):33-44.
4. Scragg R, Stewart AW, Waayer D, Lawes CMM, Toop L, Sluyter J, Murphy J, Khaw KT, Camargo CA Jr. Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial. JAMA Cardiol. 2017 Jun 1;2(6):608-616.