very low in this population, there was a suggested inverse association with supplemental vitamin E, as well.

Losonczy et al. (1996) examined vitamin E and vitamin C supplement use in 11,178 subjects (aged 67 to 105 years) who participated in the Established Populations for Epidemiological Studies of the Elderly. Vitamin E supplement use reduced the risk of all-cause mortality (relative risk [RR] = 0.66; 95 percent confidence interval [CI] 0.53 to 0.83) and risk of coronary disease mortality (RR = 0.53; 95 percent CI 0.34 to 0.84).

Additional data on the correlation between vitamin E and atherosclerosis were reported in the subjects who participated in the Cholesterol Lowering Atherosclerosis Study (CLAS), which was a randomized, placebo-controlled trial in men who had undergone coronary bypass surgery (Azen et al., 1996a,b; Hodis et al., 1995). Subjects were intensively treated with colestipol-niacin and advised to follow a cholesterol-lowering diet, or were given dietary counseling alone. Vitamin E intakes, obtained by dietary questionnaires, were inversely correlated with progression of atherosclerosis in coronary and carotid arteries. All subjects combined, those with supplementary vitamin E (100 IU/day or more) demonstrated significantly less coronary artery lesion progression than did subjects with lower vitamin E intakes from supplements (Hodis et al., 1995). Within the colestipol-niacin treated group, there was less coronary artery lesion progression among those taking vitamin E supplements (100 IU/day or more), but subjects in the placebo group showed no benefit of supplementary vitamin E (Hodis et al., 1995). A similar analysis was done on the progression of carotid artery atherosclerosis using ultrasound. Here there was no effect of vitamin E supplements in the drug-treated group, but there was an effect in the placebo group (i.e., opposite findings with respect to drug treatment and vitamin E interactions in the carotid artery from those in the coronary artery; Azen et al., 1996b).

Intervention Trials. Four large-scale, double-blind, randomized intervention trials using vitamin E have been reported. The first, the Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study (ATBC Cancer Prevention Study Group, 1994), was designed to determine whether α-tocopherol (50 mg/day of all rac-α-tocopherol acetate) and β-carotene (20 mg/day), alone or in combination, would reduce the incidence of lung cancer in a high-risk group of male smokers in Finland. Although vitamin E had no effect on the primary endpoint (lung cancer), the men taking α-tocopherol had a lower incidence of prostate cancer (see later sec-



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