Vitamin E and heart disease: a case study.

The role of nutritional epidemiology studies in the development of nutritional recommendations has been controversial, in part because individual studies supporting either side of a given issue can often be identified. Several sets of criteria for inference of a causal relation between a dietary factor and a disease from epidemiologic studies have been suggested. One such set is that of Sir Austin Bradford Hill, which includes criteria such as strength of association, dose-response relation, consistency of association, temporally correct association, specificity of association, and biological plausibility. Another set of criteria, used by the US Preventive Services Task Force, ranks evidence according to study design, designating evidence from randomized controlled trials as superior to evidence from cohort or case-control studies, which are in turn superior to evidence from ecologic studies or opinions of respected authorities. The application of these criteria to the question of whether vitamin E intake is associated with coronary heart disease is examined here. It is suggested that the epidemiologic evidence from prospective cohort studies generally supports an inverse association of vitamin E intake and risk of coronary heart disease. The information available from randomized trials is limited but suggestive of an inverse association with nonfatal, but not with fatal, coronary events. It is suggested that the application of criteria for causal inference to specific questions in nutritional epidemiology may provide clarity to seemingly contradictory information.