Vitamin E, cancer, and heart disease. Observational studies touting the protection that vitamin E may provide against cardiovascular disease and cancer don't provide evidence as reliable as that in randomized, controlled trials, say the authors of two reports on the Women's Health Study, a double-blind, placebo-controlled trial involving nearly 40,000 healthy women and 10 years of follow-up. The women were randomized into groups of almost 20,000 apiece, receiving some combination of placebo, vitamin E, and aspirin.

Unfortunately, vitamin E afforded no protection against a first major cardiovascular event or cancer, and the authors concluded that the results don't support the use of vitamin E to help prevent cardiovascular disease or cancer.

Aspirin and cancer. The primary endpoint in the aspirin component of the Women's Health Study was the overall rate of cancer. Results were similar to those in the vitamin E arm: the use of aspirin had no effect on the overall rate of cancer and virtually none on the rates of the site-specific cancers. There was a significant reduction in the rate of deaths from lung cancer that the study authors say was "likely due to data fluctuations." Their conclusion was that "aspirin at a dose of 100 mg every other day is not effective in reducing the risk of cancer in healthy women."

But wait, there's more. The Women's Health Study lasted 10 years and involved nearly 40,000 women; it was an attempt to clarify results of smaller, observational studies. And results seem to indicate that a low dosage of aspirin isn't effective for preventing cancer. However, a new report on data from the Nurses' Health Study, a trial lasting 20 years and involving more than twice as many women, shows that aspirin use may indeed help prevent colorectal cancer-and that the benefit may not appear until after 10 years of regular use.

Throughout the 20-year study, almost 83,000 nurses reported their use of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs). In women who took two or more tablets per week, the relative risk of developing colorectal cancer was 0.77. The effect seems to have been related to dose, as well, for the relative risk dropped gradually from 0.89 in those who took half a tablet to one tablet to 0.68 in those who reported taking more than 14 per week, and those who took that many for more than 10 years had a relative risk of 0.47. Results with NSAID use were similar.

The authors write that their results aren't actually in conflict with those of the Women's Health Study because their study also found that aspirin at low dosages conferred no benefit. In addition, they note that although the study "supports a possible role for aspirin in cancer prevention . . . optimal chemoprevention may require substantially higher doses of aspirin than currently recommended for the prevention of cardiovascular disease." They add that future research will "need to thoroughly consider the risk-benefit profile for aspirin/NSAID chemoprevention."

Lee IM, et al. JAMA 2005;294(1):56-65

Cook NR, et al. JAMA 2005;294(1):47-55

Chan AT, et al. JAMA 2005;294(8):914-23.