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


Vitamin E and β-carotene did not reduce lung cancer in men who smoked

ACP J Club. 1994 Nov-Dec;121:74. doi:10.7326/ACPJC-1994-121-3-074

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Source Citation

The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994 Apr 14;330:1029-35.



To determine whether daily supplementation with vitamin E (α-tocopherol) or β-carotene, or both, reduces the incidence of lung and other cancers in men who smoke.


Randomized, double-blind, placebo-controlled trial with a median follow-up of 6.1 years.


Community-based study in southwestern Finland.


29 133 men who were 50 to 69 years of age (mean age 57 y) and smoked a mean number of 20 cigarettes/d for a mean of 36 years. Exclusion criteria were history of cancer or serious disease limiting the ability to participate; taking supplements of vitamin E, vitamin A, or β-carotene in excess of predefined doses; or taking anticoagulants.


Participants were allocated to 1 of 4 supplementation regimens: vitamin E alone, 50 mg/d (n = 7286); vitamin E, 50 mg/d and β-carotene, 20 mg/d (n = 7278); β-carotene alone, 20 mg/d (n = 7282); or placebo (n = 7287).

Main outcome measures

Lung cancer, other cancers, and mortality.

Main results

876 newly diagnosed patients with lung cancer and 564 deaths caused by lung cancer were identified. No reduction in the incidence of lung cancer was observed among those who received vitamin E compared with those who did not (relative risk reduction 2%, 95% CI -14% to 12%). An excess cumulative incidence of lung cancer was observed among those who received β-carotene when compared with those who did not (relative risk increase 18%, CI 3% to 36%). No interactive effect of vitamin E and β-carotene was found. 1415 first cancers other than lung cancer were identified in 1331 patients. Fewer cancers of the prostate were diagnosed among those who received vitamin E than among those who did not. β-carotene had little or no effect on the incidence of other cancers. 3570 deaths occurred. Overall mortality was 8% higher (CI 1% to 16%) among patients who received β-carotene than among those who did not.


The incidence of lung cancer was not reduced among men who smoked after a median of 6.1 years of dietary supplementation with vitamin E or β-carotene. The incidence of lung cancer was higher among men who smoked receiving β-carotene than among those not receiving β-carotene.

Source of funding: National Cancer Institute.

For article reprint: Dr. Heinonen, Department of Public Health, University of Helsinki, P.O. Box 41, Finland or Dr. Albanes, Cancer Prevention Studies Branch, Division of Cancer Prevention and Control, National Cancer Institute, Executive Plaza North, Room 211, 900 Rockville Pike, Bethesda, MD 20892, USA. FAX 301-402-0553.


Antioxidant vitamins are increasingly promoted to patients as a method of disease prevention. With the continuing lack of success in the treatment of cancers, such as lung cancer, prevention certainly is important. Retinoids have been shown to be powerful promoters of differentiation, to reverse premalignant lesions, such as leukoplakia, and (in animal studies) to inhibit carcinogenesis at many epithelial sites (1). Appropriate agents given for sufficiently long periods of time, balancing toxicity and effect, must be chosen for prevention studies. Although retinoids have been shown to be active in preventing cancer in model systems, they are associated with important toxicity. The natural agent, β-carotene, has no acute toxic effects but also does not have established preventive activity. Thus, the lack of effect of β-carotene in preventing lung cancer in persons who smoke in the study by The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group merely confirms previously published results that this agent is ineffective in this setting. Several national trials using potentially more effective agents will be better able to answer questions about the use of antioxidants in this setting and in other cancer prevention strategies.

John R. Ellerton, MD
University of Nevada School of MedicineLas Vegas, Nevada, USA


1. Lippman SM, Benner SE, Hong WK. Cancer chemoprevention. J Clin Oncol. 1994;12:851-73.