Evaluation of Human Intervention Studies
Thus, for vitamin E in Western populations, the only available trial data in primary prevention are from the ATBC trial which shows a negative effect. In secondary prevention the accumulating trial data for vitamin E are more encouraging, particularly in terms of nonfatal endpoints, but far from conclusive in demonstrating net benefits. Each of these studie5 is open to specific criticism-the CHAOS study was too small to measure mortality hemodynamic data were limited to only 706 of the 2002 patients, the amount of vitamin E was changed during the trial, and the patients were only followed up for 17 mo on average Subjects in the ATBC study received a relatively low dose (50 mg) of vitamin E; there arE doubts about the length of treatment; and it is uncertain whether the potential vitamiL E-mediated protective effect could have any impact in such high-risk subjects (middle-age' heavy smokers).
This last uncertainty also applies to the CARET study where those treated were alread. at elevated risk for lung cancer due to exposure to asbestos or cigarette smoking; therefore preclinical cancerous change may already have been present. How should we interpret the discordance between data from cohort studies and the results so far available from clinical trials? In general, it may be that the duration of clinical trials is too short to show a benefi and that antioxidant intake over many years is required to prevent atherosclerosis. Though needs to be given to trial design; with dose, duration of treatment and follow-up period, initial antioxidant levels and dietary intake, and extent and distribution of existing atherosclerosis being taken into consideration.
Animal models have nearly always tested the effects of antioxidants on the earl. atherosclerotic lesions. Whether or not antioxidants have inhibitory effects on the later stage remains to be seen. In addition, the complex mixture of antioxidant micronutrients found in a diet high in fruit and vegetables may be more effective than large doses of one or a small number of antioxidant vitamins. It could be that several of these compounds work together but have no effect individually, or that other dietary components (e.g., trace elements) ma. be effectors of carotenoid action. The significant results linking antioxidant intake with CHI:: risk observed in cohort studies may be due to confounding by other lifestyle behaviours.
Slattery and associates examined dietary antioxidants and plasma lipids in the Coronar; Artery Risk Development in Young Adults (CARDIA) study and found that a higher intake of antioxidants was associated with other lifestyle factors such as physical activity and no: smoking. Plasma concentrations of antioxidants are linked with social class, being higher in more affluent groups. Although these variables can be individually controlled for in analyses, - may be that a complex lifelong behaviour pattern needs to be studied before conclusions regarding antioxi-dants and CHD can be made. For example, passive smoking has recently -een shown to have an atherogenic effect on LDL, yet exposure to smoke is a difficult lifestyle ariable to control for in cohort analyses and is rarely measured.
