Vitamin E and C show no cardiovascular benefit; vitamin E associated with increased hemorrhagic stroke

Neither vitamin C nor vitamin E is effective for primary prevention of cardiovascular events in men, according to results of the Physician’s Health Study II, which evaluated the risk and benefits of both vitamins as well as a multivitamin in preventing cardiovascular disease and cancer. Results relating to cancer prevention will be presented November 17 at the Frontiers in Cancer Prevention Research conference.

In terms of cardiovascular events, “There were no trends that reached significance, except for an increase in hemorrhagic stroke among vitamin E users that was only marginally significant at p=.02,” reports J. Michael Gaziano, MD (pictured), Chief, Division of Aging, Brigham and Women’s Hospital, and associate professor of medicine at Harvard Medical School, Boston.

More than half of Americans consume vitamin supplements, and vitamins E and C are the most commonly used; previous observational studies in various patient populations have indicated that vitamin E may prevent cardiovascular disease and that vitamin C may reduce coronary heart disease risk.

The Physician’s Health Study II was a double-blind, placebo-controlled, factorial design trial including 14,641 physicians, mean age 64. “This was a very healthy population,” Dr. Gaziano notes. Mean body mass index was 26 kg/m2, less than 4% were smokers, 61% exercised more than once weekly, 77.4% used daily low-dose aspirin therapy, 42% had a history of hypertension, 37% had a history of high cholesterol, and only 6% had a history of diabetes.

Study participants were first randomized to receive 400 IU vitamin E every other day or placebo, and both active treatment and placebo groups were additionally randomized to receive 500 mg vitamin C daily or placebo. The primary endpoint was a composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. There were 1,245 confirmed major cardiovascular events during the mean follow-up of 8 years with no difference between placebo groups and those taking vitamin E or C. There was no effect of vitamin use on overall mortality, although vitamin E was associated with an increased risk of the secondary endpoint of hemorrhagic stroke (HR 1.74).

The multivitamin arms of the Physician’s Health Study II will continue for an additional 3 years, Dr. Gaziano reports.

“This was a high-quality, long-term nutritional trial, and we don’t have many of these; they are essential to help us understand what to tell people to do and not to do,” says Barbara V. Howard, PhD, Medstar Research Institute, Hyattsville, Md. While the Physician’s Health Study II included only Caucasian men, smaller trials with vitamin E have not shown a gender difference.

“We do need data in other racial groups, but it is very unlikely there will be differences. The other issue that will be raised is the type of formulation,” Dr. Howard says. “I think most nutritionists would feel that it is highly unlikely that you could suddenly find a specific vitamin formulation that would be beneficial.”