Nutritional epidemiology issues in chronic disease at the turn of the century.

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Although coronary heart disease was an extremely rare diagnosis in the early years of the twentieth century, by midcentury it had become the major cause of death in Western countries. Not surprisingly, the focus of nutritional epidemiology in the 1960s and 1970s was almost exclusively on coronary heart disease. There were a few exceptions, for example, the work of Dr. Denis Burkitt, who developed a hypothesis relating inadequate intake of dietary fiber to colon cancer on the basis of his observations in Africa. The dietary factors of interest to nutritional epidemiologists were also quite limited, with the main attention being given to saturated fat, dietary cholesterol, polyunsaturated fats, and salt. Nutritionists generally believed that micronutrient inadequacy was almost absent from Western populations because clinical signs of deficiency were rarely seen. Beliefs about diet and disease in the midcentury derived primarily from animal experiments and metabolic studies in humans by using surrogate endpoints, most notably serum total cholesterol. Although animal studies had been invaluable in establishing the function of essential nutrients, the validity of animal models for chronic disease in humans is open to question until the role of diet in human disease is known. In addition, the dose-response relation, which is potentially problematic to extrapolate from animals to humans, is usually the central issue in diet-disease associations. For these reasons, data from animal studies are not a sufficient basis for nutritional guidelines in humans. Nutritional epidemiology in the midcentury primarily consisted of ecologic correlations among countries and migrant studies. While these methodological approaches were severely limited by uncontrollable confounding, they did provide powerful evidence that