Neither low-dose aspirin nor Vitamin E supplements prevent cancer in women, and Vitamin E also does little or nothing to prevent heart disease in them, according to results of a large and authoritative study released yesterday.
The findings from the nearly 40,000-person Women's Health Study add to the growing evidence that Vitamin E pills have no health benefit, but they run counter to the rising tide in favor of wider use of aspirin to prevent disease.
The study hinted that the two compounds may offer some protection against disease in some women -- results that in the case of Vitamin E were already being touted by "dietary supplement" advocates. It is also possible that a higher dose of aspirin has a benefit that was not detected with the low dose used in the clinical trial. That is still worth exploring, the researchers said.
For the moment, though, they advise against routine use of either substance by healthy women.
"When you look at the total package, I would not recommend that somebody take Vitamin E supplements for the purpose of reducing the risk of cardiovascular disease or cancer," said Julie E. Buring, an epidemiologist at Brigham and Women's Hospital in Boston who headed the study.
Nancy R. Cook, a collaborator who is also at Brigham and Women's, said: "The best thing for prevention is to follow a healthy lifestyle, eat a healthy diet, exercise and avoid smoking. But low-dose aspirin is not effective in reducing cancer incidence. We can lay that to rest."
The Women's Health Study began in the early 1990s with two goals that transcended questions about aspirin and Vitamin E.
It sought to test in women several disease-prevention strategies that had been tried in men, as extrapolating results from one sex to the other is often misleading. It also tried to get the most believable answers by randomly assigning women to take the drugs or supplements in question rather than simply observing the experience of women who, for one reason or another, chose to take them on their own.
The decade-long $40 million study met both goals, even though the substances under study proved largely ineffectual. The final report appears in today's Journal of the American Medical Association.
The 39,876 women in the study were all health care professionals. None had obvious signs of cancer or cardiovascular disease. Half were assigned to take 100 milligrams of aspirin every other day or a placebo. The standard aspirin pill, taken to relieve pain or reduce fever, is 325 milligrams. Aspirin's anti-inflammatory effects -- thought to be the source of possible cancer-preventing properties -- rise with the dose.
Half the study participants were also assigned to take 600 international units of Vitamin E every other day or a placebo. Neither they nor the scientists found out what they were taking -- two active substances or one or two placebos -- for the 10-year life of the study.
Originally, half the volunteers were also assigned to take beta carotene or a placebo. That part of the study ended after two years because a 12-year trial of that Vitamin A-like compound in men found no benefit, and two other studies suggested it may promote lung cancer.
There were 1,438 cases of cancer in women taking aspirin and 1,427 in those taking a placebo -- no significant difference. There was no effect on breast cancer incidence or death. There were slightly fewer deaths from lung cancer among women taking aspirin, a result that may have been the result of chance.
One footnote to the findings is that a higher dose of aspirin may have had a preventive effect. Aspirin helps prevent the recurrence of precancerous colon polyps, with some studies showing this is more marked at doses higher than the one used in the Women's Health Study.
In March, the researchers reported in another journal that aspirin did not lower the rate of heart attack or cardiovascular death in the women -- a result that "surprised" them, Cook said yesterday. (Aspirin did slightly lower the risk of stroke.) Elsewhere, though, there appears to be growing support for routine use of aspirin by healthy people. A team of epidemiologists last month proposed in the British Medical Journal that people older than 50 take aspirin, unless they are allergic to it. They said that cardiovascular benefits, as well as possible protection against cancer and Alzheimer's disease, outweighed aspirin's hazards, which are chiefly bleeding in the stomach and brain.
Among the women taking Vitamin E, there were 308 cancer deaths, and among those taking a placebo, there were 275.
Women older than 65 taking Vitamin E had slightly fewer heart attacks, strokes and cardiovascular deaths than those taking a placebo -- 130 vs. 176. Among women of all ages, there were also slightly fewer cardiovascular deaths with Vitamin E. Curiously, however, deaths from heart attack and stroke were not significantly reduced, suggesting the difference must lie in mortality from abnormal heart rhythms.
"Nobody has postulated that Vitamin E has an effect on arrhythmias," Buring said. "Whenever we see an unexpected finding for which we do not have a clear biological mechanism, we are cautious in our interpretations. . . . I think there's a greater likelihood this is a chance finding."
That is not the conclusion reached by the Council for Responsible Nutrition, the trade association of the dietary supplement industry.
"Something has to be going on there," said Andrew Shao, a biochemist there in charge of regulatory and scientific affairs. "I would hope that Americans who are using Vitamin E on a regular basis would continue to do so."
An analysis of several Vitamin E trials suggested supplements may increase the risk of death from all causes. The Women's Health Study did not find this. Over a decade, 636 women taking Vitamin E died, compared with 615 taking a placebo.