Experimental and epidemiological data have suggested that vitamin E supplementation may prevent cancer and cardiovascular events, according to background information in the article. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration.
Eva Lonn, M.D., of the Population Health Research Institute and McMaster University, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada, and colleagues conducted a study to evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. The randomized, double-blind, placebo-controlled trial (Heart Outcomes Prevention Evaluation [HOPE]) was initially conducted between December 21, 1993, and April 15, 1999, and included patients at least 55 years old with vascular disease or diabetes mellitus. This trial was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) to between April 16, 1999, and May 26, 2003.
Of the initial 267 HOPE centers that had enrolled 9,541 patients, 174 centers participated in the HOPE-TOO trial. Of 7,030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1,382 refused participation, 3,994 continued to take the study intervention, and 738 agreed to follow-up. Median duration of follow-up was 7.0 years. Patients received a daily dose of natural source vitamin E (400 IU) or matching placebo.
The researchers found: "In the HOPE and HOPE-TOO trials, the daily administration of 400 IU of natural source vitamin E for a median of 7.0 years had no clear impact on fatal and nonfatal cancers, major cardiovascular events, or deaths. We observed an increase in the risk of heart failure, which is of concern. Although this adverse effect of vitamin E was unexpected and cannot be confirmed at this time by other trials, our data are internally consistent. Therefore, a meta-analysis of heart failure events including all completed large vitamin E trials is strongly recommended."
"In conjunction with its lack of efficacy, the potential for harm suggested by our findings strongly supports the view that vitamin E supplements should not be used in patients with vascular disease or diabetes mellitus," the authors write. "Our study also has wider implications. There is a tendency to accept 'natural products' (e.g., vitamins) as being safe, even if they have not been proven to be effective. However, our findings emphasize the need to thoroughly evaluate all vitamins, other natural products, and complementary medicines in appropriately designed trials before they are widely used for presumed health benefits."
(JAMA. 2005;293:1338-1347. Available post-embargo at JAMA.com)
Editor's Note: For funding/support and financial disclosure information, please see the JAMA article.
Editorial: Is There Any Hope for Vitamin E?
In an accompanying editorial, B. Greg Brown, M.D., Ph.D., of the University of Washington School of Medicine, and John Crowley, Ph.D., of the University of Washington School of Public Health and Community Medicine, Seattle, discuss the findings of the HOPE-TOO trial.
"Why is this report important? First, by extending HOPE and adding to the growing list of neutral prospective vitamin E trials, this report effectively closes the door on the prospect of a major protective effect of long-term exposure to this supplement, taken in moderately high dosage, against complications of atherosclerosis and overall cancer incidence. Second, in doing so, HOPE-TOO reemphasizes the importance of controlled clinical trials for testing important hypotheses deriving from basic biological findings or from epidemiological observations. The latter can mislead; well-designed clinical trials rarely do."
"The hopes for vitamin E alone or in combination with vitamin C and beta carotene have been diminished by a compelling body of clinical trial evidence, and by certain adverse effects with plausible biological explanation. These hopes are now confined to modest expectations for specific disorders and there are concerns about adverse effects. While there is solid evidence linking oxidative processes to human disease (as well as to normal biological function), the details of these processes and of proposed therapeutic or preventive interventions appear to need considerable rethinking," they conclude.
(JAMA. 2005;293:1387-1390. Available post-embargo at JAMA.com)