Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Vitamins E and C and β-carotene may not reduce cardiovascular mortality

ACP J Club. 1996 Mar-April;124:44. doi:10.7326/ACPJC-1996-124-2-044

Source Citation

Jha P, Flather M, Lonn E, Farkouh M, Yusuf S. The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med. 1995 Dec 1;123:860-72. [PubMed ID: 7486470]



To determine whether antioxidant vitamins (vitamins E and C and β-carotene) reduce cardiovascular disease and overall mortality.

Data Sources

Studies were identified through MEDLINE (1965 to 1994); Science Citation Index; bibliographies of review articles, included studies, and textbooks; and contact with experts. MEDLINE search terms were vitamin E, vitamin C, β-carotene, vitamins, antioxidants, coronary heart disease, cerebrovascular disease, peripheral vascular disease, atherosclerosis, and mortality.

Study Selection

Randomized controlled trials or cohort studies were selected if they provided data on the specific type and intake of antioxidants and on outcomes and if > 100 participants were included.

Data Extraction

Data were extracted on study type, age of participants, length of follow-up, type and dose of antioxidant, and outcomes.

Main Results

The findings differed for cohort studies and randomized controlled trials. Vitamin E was studied in 4 cohorts in 3 studies; 3 cohorts showed a reduction in cardiovascular mortality. 1 randomized controlled trial studied vitamin E, and 1 studied vitamin E plus β-carotene and selenium; neither showed a difference in mortality. β-carotene was studied in 6 cohorts in 5 studies; 4 cohorts showed a reduction in cardiovascular mortality. 3 randomized controlled trials studied β-carotene; 2 did not show a reduction in cardiovascular mortality. Vitamin C was studied in 8 cohorts in 6 studies; 1 cohort showed a reduction in cardiovascular mortality, and 1 cohort showed a reduction in mortality from stroke. Neither of the 2 randomized controlled trials of vitamin C showed a reduction in total or cardiovascular mortality. 8 trials of antioxidant vitamins that include more than 126 000 patients are currently being done.


Completed randomized controlled trials do not show that antioxidants (vitamins E and C and β-carotene) reduce mortality from cardiovascular disease.

Sources of funding: Medical Research Council of Canada and Heart and Stroke Foundation, Canada.

For article reprint: Dr. P. Jha, Human Development Department, The World Bank, 1818 H Street North West, Washington, DC 20433, USA. FAX 202-614-0068.

Updated Commentary

Since the publication of the original commentary on vitamin E and the risk for cardiovascular disease, there have been a number of publications that confirm the cautions that I have raised. Current data indicate that vitamin E supplementation does not render additional cardiovascular benefit.

Results from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Prevenzione trial (1) show that dietary supplementation with n-3 polyunsaturated fatty acids have a significant benefit in terms of reduction of major cardiac events, death, myocardial infarction, and stroke. Patients taking vitamin E in a dose of 300 IU had no benefit. Similarly, the results from the Heart Outcomes Prevention Evaluation trial (2) showed no benefit to the vitamin E arm of the trial.

2 other recent trials further increase the body of evidence suggesting the vitamin E has no benefit. Meager and colleagues (3) examined a number of indicators of oxidative stress in healthy persons treated with vitamin E and showed no reduction in those measures in the vitamin E-treated group. The Collaborative Group of the Primary Prevention Project (4) also showed no benefit to vitamin E in a higher-risk group.

Taken together, these data provide adequate evidence that routine supplementation with vitamin E does not render additional cardiovascular protection. Current data in our present population would indicate that a balanced diet provides adequate amounts of vitamin E for healthy persons and patients with cardiovascular disease.

Dennis L. DeSilvey, MD
University of VirginiaCharlottesville, Virginia, USA


1. GISSI Prevenzione Investigators. GISSI-Prevenzione Trial. Lancet. 1999;354:447-55.

2. Yusuf S, Sleigth P, Pogue J, et al., for the Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular event in high-risk patients. N Engl J Med. 2000;342:145-53.

3. Meagher EA, Barry OP, Lawson JA, Rokach J, FitzGerald GA. Effects of vitamin E of lipid peroxidation in healthy persons. JAMA. 2001;285:1178-82.

4. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet. 2001;357:89-95.

Editor's Note

Readers may also be interested in a previous ACP Journal Club report on the ATBC study (6) that showed an increase in lung cancer and total mortality among men who smoked while taking β-carotene.

1. Vitamin E and β-carotene did not reduce lung cancer in men who smoked. ACP J Club. 1994 Nov-Dec;121:74. Abstract of: The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994;330:1029-35.