Health for life

Approximately one-third of Americans take a daily multivitamin, but little is known about a multivitamins long-term affect on chronic diseases. Now, new research from Brigham and Womens Hospital (BWH) finds that daily multivitamin use does not reduce the risk of cardiovascular disease in men. A similar BWH study, announced last month, found daily multivitamin use can reduce a mans risk of cancer by 8 percent. The cardiovascular disease findings will be presented Nov. 5 at the American Heart Associations Scientific Sessions 2012 and published simultaneously in the Journal of the American Medical Association.

"The findings from our large clinical trial do not support the use of a common daily multivitamin supplement for the sole purpose of preventing cardiovascular disease in men," said Howard D. Sesso, ScD, lead author and an associate epidemiologist in the Division of Preventive Medicine at BWH. "The decision to take a daily multivitamin should be made in consultation with ones doctor and consideration given to an individuals nutritional status and other potential effects of multivitamins, including the previously reported modest reduction in cancer risk."

Researchers enrolled nearly 15,000 men over the age of 50 in the study and followed them for more than 10 years. The men were randomly assigned to take either a multivitamin or a placebo every day which ensured that both treatment groups were identical with respect to risk factors for cardiovascular disease. The men self-reported episodes of heart attacks, strokes and cardiovascular disease, and a panel of physicians reviewed and confirmed their events with medical records. Researchers then compared the group that took the multivitamin with the group that took the placebo and found no significant impact on risk of heart attack, stroke, or cardiovascular mortality. Additionally, the effect of a daily multivitamin on major cardiovascular events did not differ on participants with a baseline history of cardiovascular disease and those who were initially free of cardiovascular disease.

J. Michael Gaziano, MD, chief of the Division of Aging at BWH, investigator at VA Boston and senior author of the study, said, "Since so many Americans take daily multivitamins, studies like this are key to providing us with valuable information about what specific benefits multivitamins do or do not provide in terms of their long-term impact on chronic diseases. For cardiovascular disease, we must continue to emphasize a heart-healthy diet, physical activity, smoking cessation and regular screening for cardiovascular risk factors."

In a randomized trial that included nearly 15,000 male physicians, long-term daily multivitamin use resulted in a modest but statistically significant reduction in cancer after more than a decade of treatment and follow-up, according to a study appearing in JAMA. The study is being published early online to coincide with its presentation at the Annual American Association for Cancer Research Frontiers in Cancer Prevention Research meeting.

"Multivitamins are the most common dietary supplement, regularly taken by at least one-third of U.S. adults. The traditional role of a daily multivitamin is to prevent nutritional deficiency. The combination of essential vitamins and minerals contained in multivitamins may mirror healthier dietary patterns such as fruit and vegetable intake, which have been modestly and inversely associated with cancer risk in some, but not all, epidemiologic studies. Observational studies of long-term multivitamin use and cancer end points have been inconsistent. To date, large-scale randomized trials testing single or small numbers of higher-dose individual vitamins and minerals for cancer have generally found a lack of effect," according to background information in the article. "Despite the lack of definitive trial data regarding the benefits of multivitamins in the prevention of chronic disease, including cancer, many men and women take them for precisely this reason."

J. Michael Gaziano, M.D., M.P.H., of Brigham and Womens Hospital and Harvard Medical School, Boston, (and also Contributing Editor, JAMA), and colleagues analyzed data from the Physicians Health Study (PHS) II, the only large-scale, randomized, double-blind, placebo-controlled trial testing the long-term effects of a common multivitamin in the prevention of chronic disease. The trial includes 14,641 male U.S. physicians, initially age 50 years or older, including 1,312 men with a history of cancer at randomization, who were enrolled in a multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011. Participants received a daily multivitamin or equivalent placebo. The primary measured outcome for the study was total cancer (excluding nonmelanoma skin cancer), with prostate, colorectal, and other site-specific cancers among the secondary end points.

PHS II participants were followed for an average of 11.2 years. During multivitamin treatment, there were 2,669 confirmed cases of cancer, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer, with some men experiencing multiple events. A total of 2,757 (18.8 percent) men died during follow-up, including 859 (5.9 percent) due to cancer. Analysis of the data indicated that men taking a multivitamin had a modest 8 percent reduction in total cancer incidence. Men taking a multivitamin had a similar reduction in total epithelial cell cancer. Approximately half of all incident cancers were prostate cancer, many of which were early stage. The researchers found no effect of a multivitamin on prostate cancer, whereas a multivitamin significantly reduced the risk of total cancer excluding prostate cancer. There were no statistically significant reductions in individual site-specific cancers, including colorectal, lung, and bladder cancer, or in cancer mortality.

Daily multivitamin use was also associated with was a reduction in total cancer among the 1,312 men with a baseline history of cancer, but this result did not significantly differ from that observed among 13,329 men initially without cancer.

The researchers note that total cancer rates in their trial were likely influenced by the increased surveillance for prostate-specific antigen (PSA) and subsequent diagnoses of prostate cancer during PHS II follow-up starting in the late 1990s. "Approximately half of all confirmed cancers in PHS II were prostate cancer, of which the vast majority were earlier stage, lower grade prostate cancer with high survival rates. The significant reduction in total cancer minus prostate cancer suggests that daily multivitamin use may have a greater benefit on more clinically relevant cancer diagnoses."

The authors add that although numerous individual vitamins and minerals contained in the PHS II multivitamin study have postulated chemopreventive roles, it is difficult to definitively identify any single mechanism of effect through which individual or multiple components of their tested multivitamin may have reduced cancer risk. "The reduction in total cancer risk in PHS II argues that the broader combination of low-dose vitamins and minerals contained in the PHS II multivitamin, rather than an emphasis on previously tested high-dose vitamins and mineral trials, may be paramount for cancer prevention. … The role of a food-focused cancer prevention strategy such as targeted fruit and vegetable intake remains promising but unproven given the inconsistent epidemiologic evidence and lack of definitive trial data."

"Although the main reason to take multivitamins is to prevent nutritional deficiency, these data provide support for the potential use of multivitamin supplements in the prevention of cancer in middle-aged and older men," the researchers conclude.