New NEJM Trial on Vitamin D
I am not sure if all of you saw the NEJM trial on the Vitamin D supplementation and the prevention of cancer and cardiovascular disease. In the VITAL study (funded by NIH in the United states) they looked at Vitamin D3 at 2000IU per day and marine Omega-3 fatty acids 1 gram per day for the prevention of cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. It randomized 25,871 patients including 5106 black.
Primary and Secondary End Points
Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes).
Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. This trial reports the results of the comparison of vitamin D with placebo for an average follow-up of 5.3 years.
No Impact on Cardiovascular Disease
Supplementation with vitamin D was not associated with a lower risk of cardiovascular disease. 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 Odds Ratio (OR) of each of the major CV events were:
- Cardiovascular events plus coronary revascularization, 0.96 (95% CI, 0.86 to 1.08)
- Myocardial infarction, 0.96 (95% CI, 0.78 to 1.19)
- Stroke, 0.95 (95% CI, 0.76 to 1.20)
- Death from cardiovascular causes, 1.11 (95% CI, 0.88 to 1.40)
No Impact on Cancer Risk
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). In their analysis of cancer risk, they report OR of:
- Death from cancer (341 deaths), 0.83 (95% CI, 0.67 to 1.02)
- Breast cancer, 1.02 (95% CI, 0.79 to 1.31)
- Prostate cancer, 0.88 (95% CI, 0.72 to 1.07)
- Colorectal cancer, 1.09 (95% CI, 0.73 to 1.62)
No Impact on Death from Any Cause
In the analysis of death from any cause (978 deaths), the hazard ratio was 0.99 (95% CI, 0.87 to 1.12)
What Does this Mean for Practice?
This was a well-researched trial that was funded by the National Institute of Health in the US. I think that we have to be careful in what we recommend supplements for, based on this and other research. The good thing from this trial is the overall risk of adverse events was found to be the same as placebo.
I think we can continue to recommend the 400-1000IU daily of Vitamin D3 as recommended by the Osteoporosis Canada 2010 guidelines, but we should be cautious of stating that there are any other additional benefits for the heart or cancer risk.
References
Manson, JoAnn E., Nancy R. Cook, I-Min Lee, William Christen, Shari S. Bassuk, Samia Mora, Heike Gibson, et al. “Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease.” New England Journal of Medicine 380, no. 1 (January 3, 2019): 33–44. https://doi.org/10.1056/NEJMoa1809944.
Papaioannou, Alexandra, Suzanne Morin, Angela M. Cheung, Stephanie Atkinson, Jacques P. Brown, Sidney Feldman, David A. Hanley, et al. “2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada: Summary.” CMAJ 182, no. 17 (November 23, 2010): 1864–73. https://doi.org/10.1503/cmaj.100771.