Physicians’ Health Study II Finds No Clear Link between Multivitamin Use, Reduced CVD Risk, in Subjects with Less-Nutritious Diets

Apr 14, 2017

In a newly published, secondary analysis of the Physicians’ Health Study II1, researchers posited that multivitamin supplementation did not help to prevent the risk of cardiovascular disease (CVD), even in subjects who were found to have less-nutritious diets.

The Physicians’ Health Study II was a large, randomized, double-blind, placebo-controlled study started in 1997 examining whether dietary supplements, including a multivitamin, could help to prevent CVD, cancer, age-related eye disease, and cognitive decline in study subjects comprising 14,641 U.S. male physicians aged 50 years and older. In 2012, researchers published results finding that daily multivitamin supplementation “modestly but significantly” reduced the risk of cancer.

In the new, secondary analysis published in April in JAMA Cardiology, researchers determined overall, based on 11 years of follow-up, that multivitamin supplementation did not reduce subjects’ risk of CVD, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality; in addition, the researchers also did not find any clear benefit that multivitamin supplementation helped to reduce risk in subjects with poor baseline levels of nutrition.

Based on their analysis, researchers concluded, “The results suggest that baseline nutritional status does not influence the effect of randomized long-term multivitamin use on major CVD events.”

“Intuitively, many had thought that men with 'poor' nutritional status at baseline may benefit more from long-term multivitamin use on cardiovascular outcomes; however, we did not see any evidence for this in our recent analysis,” said one of the study’s authors, Howard Sesso, ScD, MPH, of the Division of Preventive Medicine and the Division of Aging at Brigham and Women’s Hospital (Boston, MA), which conducted the study. "Given the continued high prevalence of multivitamin use in the U.S., it remains critical for us to understand its role on nutritional status and other long-term health outcomes through clinical trials such as PHS II and other new research initiatives.”

The researchers did note, “Future studies are needed to investigate the role of baseline nutritional biomarkers on the effect of multivitamin use on CVD and other outcomes.”

The Physicians’ Health Study II was funded by the National Institutes of Health and other sponsors, including the Council for Responsible Nutrition (CRN; Washington, DC).

Responding to the study’s findings, CRN’s senior vice president of scientific and regulatory affairs, Duffy MacKay, ND, cautioned consumers to “manage their expectations” when it comes to multivitamins and to remember the benefits multivitamins can provide.

“Science has already demonstrated the value of the multivitamin, and so while we are disappointed to see the null results of this study, by no means are we discouraged,” MacKay said in a press release. “The multivitamin serves many roles—from filling nutrient gaps to preventing neural tube birth defects—and is trusted as a go-to nutrition insurance policy by nearly a hundred million Americans each year. Only four years ago, the Physicians’ Health Study II found the multivitamin may have potential benefit for the prevention of cancer in a well-nourished male population. The multivitamin can do a lot, but we must remember that it cannot do everything, and this well-designed study, which found no consistent impact of nutritional status on the effect of multivitamin use on cardiovascular disease risk, reinforces this fact and reminds us to manage expectations for the role of multivitamins.”

In addition, MacKay posited that the U.S. physicians included in the Physicians’ Health Study II may have already had healthier diets than the general U.S. population, “which could be why the researchers did not find any additional benefit from a nutritional intervention.” He suggested that the study could have had different results if it was conducted in subjects “that represented a wider range of America’s dietary habits.”

  1. Rautiainen S et al., “Effect of baseline nutritional status on long-term multivitamin use and cardiovascular disease risk: a secondary analysis of the Physicians' Health Study II randomized clinical trial,” JAMA Cardiology. Published online April 5, 2017.