Vitamin E Supplementation And Cardiovascular Events

Nutrition Research Newsletter, March, 2000

As the development of atherosclerosis is more fully understood, it looks like oxidative modification of low-density lipoproteins is an important step in the development and progression of this disease. Observational studies have shown that one antioxidant, vitamin E, lowers the rate of coronary events and the progression of coronary artery lesions. However, these observational studies cannot determine whether these proposed benefits of vitamin E are due to the vitamin or to other lifestyle and dietary factors.

The Heart Outcomes Prevention Evaluation Study was designed to evaluate the effects of a high dose of vitamin E from natural sources and ramipril, an angiotensin converting enzyme (ACE) inhibitor, over a five-year period, on cardiovascular events. The findings from the vitamin E section of the study were recently discussed in the New England Medical Journal.

A total of 2545 women and 6996 men greater than 55 years of age and at high risk for CVD participated in the study. Due to the two-by-two factorial design, patients received 400 IU of vitamin E daily from natural sources or a placebo and either ramipril or a placebo for a mean of four and a half years. The primary outcome was either a myocardial infarction (MI), a stroke, or death from cardiovascular causes. Secondary outcomes included death from any cause, hospitalization for unstable angina or congestive heart failure (CHF), revascularization or limb amputation, complications of diabetes, and cancer.

Data showed that compliance with treatment was high. There was no significant difference between the vitamin E and placebo group in numbers of deaths from cardiovascular causes, 16.2% vs. 15.5%, respectively, or in number of MIs, deaths from CHD, or strokes. Vitamin E also had no effect on the primary outcome of either those who were or were not receiving ramipril. There were also no significant differences among groups in the incidence of secondary outcomes. Vitamin E had no adverse side effects on the subjects, including no increase in hemorrhagic stroke.

During the study's follow-up period of four to six years, vitamin E did not decrease the incidence of cardiovascular events among patients with a high risk for cardiovascular disease. The study had many strengths, including high rates of compliance, a high statistical power due to the large number of primary outcomes, and a large number of secondary outcomes. One hypothesis for the lack of beneficial findings is that antioxidants may have to be used for more than five years to see benefits, since the primary mechanism of antioxidants is in the prevention of new lesions. Therefore, this study population may not have seen results because they were not researched for a long enough period of time. Another possible explanation for the lack of benefit of vitamin E is that it was used alone and not in combination with other antioxidants. Vitamin E may need other cofactors to provide beneficial results with cardiovascular events.

The Heart Outcomes Prevention Evaluation Study Investigators, Vitamin E Supplementation and Cardiovascular Events in High-Risk Patients, N Eng J Med 342 (3): 154-160 (January 20, 2000) [Correspondence: Dr. Salim Yusuf, Canadian Cardiovascular Collaboration Project Office, Hamilton General Hospital, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada. E-mail: yusufs@fhs.mcmaster.ca.]