Dietary fat and risk of chronic disease: mechanistic insights from experimental studies.

The primary nutritionally linked diseases are coronary heart disease, stroke and cancers of the stomach, colon, pancreas, prostate, breast, ovary, and endometrium. Dietary fats operate through a promoting mechanism. An S-shaped dose-response curve with a threshold has been demonstrated in models of breast and colon cancer in which the standard Western fat intake of 40% of energy yields a high level of promotion, and reduction of fat to 10% to 20% of energy (the traditional Japanese fat intake) has a low promoting action. In models of breast and colon cancer, saturated fats such as beef fat or lard, and monounsaturated oils, such as olive oil, display only a weak promoting effect, with the incidence of induced tumors being similar at intake levels of 40% and 10% of energy. On the other hand, the n-6-polyunsaturated oils display a strong promoting effect. Such findings may have a parallel in the low but definitely increasing slope of postmenopausal breast cancer incidence in the past 30 years as the American public decreased saturated fat intake to avoid heart disease and increased use of the n-6-polyunsaturated oils. Mechanisms underlying the cancer-promoting effect in the colon stem from increased hepatic production of bile acids, which are transferred to the intestinal tract via the bile. Ingestion of 40% fat calories yields higher concentrations of bile acids in the colon than lower levels of dietary fat ingestion. Cancer in the mammary gland is promoted through higher concentrations of fats and phospholipids in the gland as well as increased levels of estrogen secondary to production by the ovary and other endocrine tissues that, in turn, affect the generation of pituitary hormones such as prolactin and growth hormone. The n-3-fats, as found in fish and fish oils, have a pronounced inhibitory effect in models of colon and breast cancer, presumably through their shifting of prostaglandin metabolism to the generation of prostaglandins, which lower cell proliferation potential and, thus, decrease promotional effects. The role of dietary fat as a promoter can be modified by other nutritional components. Finally, one of the best pieces of evidence for an enhancing effect of many dietary fats in the nutritionally linked cancers is the current increase in the incidence of these diseases in Japan as the nutritional habits of people in that country become more Westernized.