Vitamin E supplementation shows no overall benefit for major cardiovascular events or cancer


In an article in the July 6 JAMA, I-Min Lee, M.B.B.S., Sc.D., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues analyzed data from the vitamin E component of the Women's Health Study, which tested whether vitamin E supplementation decreases the risk of cardiovascular disease and cancer among healthy women.

According to background information in the article, previous observational studies have indicated that vitamin E may be beneficial in lowering the risk for some cardiovascular diseases; and high antioxidant intake has been linked to reduced cancer rates. For small to moderate effects, however, the amount of uncontrolled and uncontrollable confounding inherent in observational studies can be as large as the postulated benefit, so randomized clinical trials represent the most reliable study design strategy. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons. By 1997, despite a lack of randomized trials, 44 percent of U.S. cardiologists reported routine use of antioxidant supplements, primarily vitamin E, compared with 42 percent who routinely used aspirin for the primary prevention of CVD.

In this component of the Women's Health Study, 39,876 apparently healthy U.S. women aged at least 45 years were randomly assigned to receive 600 IU of natural-source vitamin E on alternate days or placebo, and were followed up for an average of 10.1 years.

The researchers found with the vitamin E group, there was no significant effect on major cardiovascular events, on the incidences of heart attack or stroke, as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a 24 percent reduction. There was no significant effect on the incidences of total cancer or breast, lung, or colon cancers. Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total death.

"In conclusion, the WHS does not support recommending vitamin E supplementation for CVD or cancer prevention among healthy women. This large trial supports current guidelines stating that use of antioxidant vitamins is not justified for CVD risk reduction. The WHS findings should be viewed in the context of the available randomized evidence, as well as data that should be available over the next several years from ongoing trials, including the Physicians' Health Study, which will provide data on primary prevention in men. At present, in the primary prevention of CVD and cancer, therapeutic lifestyle changes including a healthy diet and control of major risk factors remain important clinical and public health strategies," the authors conclude.

(JAMA. 2005;294:56-65. Available pre-embargo to the media at

Editor's Note: For funding/support and financial disclosure information, please see the JAMA article.

Editorial: Vitamin E and Cardiovascular Health

In an accompanying editorial, Rita F. Redberg, M.D., M.Sc., of the University of California, San Francisco, discusses the study by Lee et al.

"Perhaps it is time to consider devoting some of the limited resources necessary to perform randomized controlled trials to other pressing, unanswered questions in the field of cardiovascular disease prevention in women. With the publication of the WHS vitamin E results, it is time to redirect attention to interventions that have been shown to or could provide significant benefit."

" vitamin E enters the category of therapies that were promising in epidemiologic and observational studies but failed to deliver in adequately powered randomized controlled trials. As in other studies, the 'healthy user' bias must be considered, i.e., the healthy lifestyle behaviors that characterize individuals who care enough about their health to take various supplements are actually responsible for the better health, but this is minimized with the rigorous trial design. It is estimated that almost 1 million preventable deaths per year are due to smoking, poor diet, and physical inactivity. Perhaps the most important outcome of the WHS reports will be greater recognition that it is time to concentrate on teaching nutrition, promoting regular physical activity, and strongly encouraging smoking cessation and particularly increasing outreach to women of racial and ethnic minorities," Dr. Redberg writes. "[These] are underused but proven prevention strategies for heart disease. Interestingly, these positive lifestyle changes are also associated with the prevention of cancer and Alzheimer disease."

(JAMA. 2005;294:107-109. Available pre-embargo to the media at

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