Women at high risk for cardiovascular disease who take ascorbic acid, vitamin E, and beta-carotene in hopes of preventing cardiovascular events may want to rethink that strategy.
A large, long-term study found that there is no overall preventive effect of ascorbic acid, vitamin E, or beta-carotene on cardiovascular events among women at high risk for cardiovascular disease, whether taken alone or in combination.
“While additional research into combinations of agents, particularly for stroke, may be of interest, widespread use of these individual agents for cardiovascular protection does not appear to be warranted,” wrote the researchers, who were led by Nancy R. Cook, Sc.D., of the division of preventive medicine at Brigham and Women's Hospital, Boston.
For the randomized trial, known as the Women's Antioxidant and Cardiovascular Study, Dr. Cook 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 cardiovascular disease or three or more risk factors for CVD.
The mean age of the 8,171 women was 61 years. Of these, 5,238 (64%) had a prior cardiovascular event and 2,933 (36%) 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.
Dr. Cook and her associates reported that during a mean 9.4 years of follow-up, 1,450 women had a total of 1,856 cardiovascular disease events. These included 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 cardiovascular disease-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 women in the study. 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 among women taking both ascorbic acid and vitamin E, compared with those in the placebo group for both agents (RR 0.69), suggesting a two-way interaction.
On average, the reported compliance for each antioxidant was 76% at 4 years and 68% at 8 years of follow-up, which is one limitation of the study. In addition, the researchers wrote that “mortality information follow-up was virtually complete through 2003 and then 93% complete for the remaining two years.”
The study was supported by a grant from the National Heart, Lung, and Blood Institute.
Cognis supplied the vitamin E and its placebo, while BASF supplied all other supplements and their placebos. Neither company had influence on the design or conduct of the study.