Jury Out on Vitamin D Supplementation for Heart Health

Megan Brooks

December 19, 2011

December 19, 2011 — There is no solid evidence from clinical trials that vitamin D supplementation can prevent cardiovascular disease (CVD), conclude the coauthors of a narrative review of research published in the last 26 years.

The article, from Cora McGreevy, MB, BCh, BAO, and David Williams, MB, BAO, BCh, PhD, of the Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, was published online December 19 in the Annals of Internal Medicine.

"There is emerging evidence from observational studies that there may be biological links between vitamin D deficiency, cardiovascular disease, and endothelial dysfunction," Dr. McGreevy told Medscape Medical News.

However, few randomized, controlled trials have evaluated the effect of vitamin D replacement on cardiovascular outcomes, and the results have been "inconclusive or contradictory," Dr. McGreevy and Dr. Williams report.

"Carefully designed randomized, controlled trials are essential to evaluate the role of vitamin D supplementation in reducing cardiovascular disease," they conclude.

Thomas J. Wang, MD, from the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, who has studied vitamin D deficiency and the risk of CVD, agrees and told Medscape Medical News that "more (larger) trials are needed. Until then, the jury is still out."

Mixed Bag

Vitamin D deficiency is prevalent worldwide, particularly in northern latitudes, although there is some controversy about what level of 25-hydroxyvitamin D actually constitutes deficiency. Other populations at risk include elderly persons, women, nursing home residents, and children in susceptible geographic areas such as the Middle East and Asia.

There is experimental evidence linking vitamin D deficiency with hypertension, myocardial infarction, and stroke, as well as other cardiovascular-related diseases, including the development of atherosclerosis and endothelial dysfunction, Dr. McGreevy and Dr. Williams note in their report.

Clinical studies support a role for vitamin D in maintaining cardiovascular health through direct action of the vitamin on cardiomyocytes and indirect actions on circulating hormone and calcium levels, they say.

Associations between low vitamin D levels and increased plasma renin activity, coronary artery calcification, blood pressure, and CVD have also emerged in prior studies.

A meta-analysis published in 2010 analyzed data from 17 prospective cohort studies and randomized trials. The authors found that moderate to high doses of vitamin D supplements may reduce the risk for CVD, with benefits mainly seen in patients on dialysis. However, only 1 study involving the general population showed consistent reductions in CVD after vitamin D supplementation.

A systematic review of 13 observational studies also published in 2010 examined the association of vitamin D status with cardiometabolic outcomes (ie, type 2 diabetes, hypertension, or CVD). It concluded that the association is uncertain; the trials showed no clinically significant effect of vitamin D supplementation, although the heterogeneity of the studies hampered the results.

A meta-analysis of 51 trials published in 2011 failed to demonstrate a statistically significant reduction in mortality or cardiovascular risk in relation to vitamin D status.

"Touted" Benefits Unsupported for Now

For now, "no clear evidence indicates that vitamin D supplementation has a role to play in the prevention of cardiovascular disease, outside of clinical studies," Dr. McGreevy and Dr. Williams conclude.

Mohammad Hassan Murad, MD, MPH, from the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News that vitamin D "clearly strengthens bones and muscles; however, its touted effects on other diseases (particularly heart disease) are not supported by evidence at the present time."

"There are a lot of theories and potential mechanisms suggested to explain how vitamin D would improve cardiovascular outcomes, but none are proven in a randomized trial setting," Dr. Murad said.

Dr. McGreevy said that although there are "some schools of thought that suggest that vitamin D may merely be a surrogate marker for poor health status, further well designed large studies are needed to investigate the role of vitamin D supplementation in the prevention of cardiovascular disease."

"These trials should target the hypotheses generated by the previous observational studies and evaluate the potential role of vitamin D supplementation in cardiovascular protection," she said.

Disclosure information for Dr. McGreevy and Dr. Williams can be found on the journal's Web site. Dr. Wang and Dr. Murad have disclosed no relevant financial relationships.

Ann Intern Med. 2011;155:820-826. Abstract