Vitamin E, Beta Carotene and Lung Cancer

Background

Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta carotene, are associated with a reduced risk of lung cancer.

Methods

We performed a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers 50 to 69 years of age from southwestern Finland were randomly assigned to one of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Follow-up continued for five to eight years.

Results

Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent).

We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha-tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not, primarily because there were more deaths from lung cancer and ischemic heart disease.

Conclusions

We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene. In fact, this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.

Previous studies have suggested that higher intakes of vitamin E (alpha-tocopherol) and beta carotene may be associated with a reduced risk of lung cancer. In particular, epidemiologic studies have linked the intake of vegetables rich in beta carotene with a lower risk of cancer (especially lung cancer) and have suggested that certain micronutrients are inhibitors of cancer1,2. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study was a randomized, double-blind, placebo-controlled primary-prevention trial undertaken to determine whether supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer in male smokers. A secondary outcome of interest was the incidence of other cancers. Lung cancer was deemed a particularly appropriate target for this trial because of its high incidence, its generally poor prognosis, and the existence of a well-defined high-risk population (i.e., smokers)3. In this report we describe the initial overall results of the study, which was conducted in Finland as a joint project of the National Public Health Institute of Finland and the U.S. National Cancer Institute.