Besides questioning whether vitamins help, "we have to worry about potential harm," said Barbara Howard, a nutrition scientist at MedStar Research Institute of Hyattsville, Md.
She has no role in the research but reviewed and discussed it Sunday at an American Heart Association conference. Results also were published online by the Journal of the American Medical Association.
About 12 percent of Americans take supplements of C and E despite growing evidence that these antioxidants do not prevent heart disease and may even be harmful.
Male smokers taking vitamin E had a higher rate of bleeding strokes in a previous study, and several others found no benefit for heart health.
As for vitamin C, some research suggests it may aid cancer, not fight it. A previous study in women at high risk of heart problems found it did not prevent heart attacks.
Few long-term studies have been done. The new one is the Physicians Health Study, led by Drs. Howard Sesso and J. Michael Gaziano of Harvard-affiliated Brigham and Women's Hospital in Boston.
It involved 14,641 male doctors, 50 or older, including 5 percent who had heart disease at the time the study started in 1997. They were put into four groups and given either vitamin E, vitamin C, both, or dummy pills. The dose of E was 400 international units every other day; C was 500 milligrams daily.
After an average of eight years, no difference was seen in the rates of heart attack, stroke or heart-related deaths among the groups.
However, 39 men taking E suffered bleeding strokes versus only 23 of the others, which works out to a 74 percent greater risk for vitamin-takers.
The study was funded by the National Institutes of Health and several vitamin makers. Results were so clear that they would be unlikely to change if the study were done in women, minorities, or with different formulations of the vitamins, Howard said.
"In these hard economic times, maybe we can save some money by not buying these supplements," she said.
A second study found that vitamins B-12 and B-9 (folic acid) did not prevent heart disease either, supporting the results of previous trials. That study involved more than 12,000 heart attack survivors and was led by Dr. Jane Armitage of the University of Oxford in England.