A large, long-term study has found there is no overall preventive effect of ascorbic acid, vitamin E, or beta-carotene on cardiovascular events in women at high risk for cardiovascular disease, whether taken alone or in combination.
For the randomized trial, known as the Women's Antioxidant and Cardiovascular Study, Nancy R. Cook, Sc.D., of the division of preventive medicine at Brigham and Women's Hospital, Boston, and her associates tested the effects of ascorbic acid, vitamin E, and beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death in 8,171 women aged 40 years or older. All had a history of CVD or three or more risk factors for CVD.
The mean age of the 8,171 women was 61 years. Of these, 5,238 had a prior cardiovascular event and 2,933 had three or more CVD risk factors. In a two-by-two-by-two factorial study design, each study participant took 500 mg per day of ascorbic acid (synthetic vitamin C), 600 IU of vitamin E every other day, and 50 mg of beta-carotene every other day. The women took the supplements for a mean of 9.4 years, starting in 1995–1996 and ending on Jan. 31, 2005 (Arch. Intern. Med. 2007;167:1610–8).
Compliance was defined as taking at least two-thirds of the study pills. The researchers relied on patient self-reports for compliance twice during the first year, then annually until the end of the trial.
During a mean 9.4 years of follow-up, 1,450 women had a total of 1,856 CVD events. These included 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 CVD-related deaths. The researchers found no overall effect of ascorbic acid, vitamin E, or beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death among the women. However, a marginally significant reduction in the primary outcome from vitamin E use was observed in a subgroup of women with a history of CVD (relative risk 0.89).
There were no overall effects of the agents on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD-related death. However, a significant reduction in stroke was seen in women taking both ascorbic acid and vitamin E.
The study was supported by a National Heart, Lung, and Blood Institute grant. Cognis supplied the vitamin E and placebo; BASF supplied all other supplements and placebos. Neither had influence on the study design or conduct.