Lipid and hemostatic profiles have etiologic importance in atherogenesis and are influenced by diet. The proposed study addresses key unresolved issues in the effects of fat and other diet constituents on blood lipid (total cholesterol, LDL-C, HDL-C, triglycerides) and hemostatic responses (fibrinogen, factor VII, plasminogen activator inhibitor, Beta-thromboglobulin and platelet factor 4). The proposed research includes a series of tightly controlled human nutrition feeding studies conducted within a multicenter feeding trial mechanism with a common protocol. The focus of this project is to determine the optimal composition for a lipid lowering diet. An integrated series of five 6-month Latin square design feeding studies will be conducted. The diets to be tested in 4 experiments with 5-week feeding periods evaluate modifications to the American Heart Association Step 1 diet (30% of Kcal from fat) and the typical American diet (37% Kcal from fat). Contrasts of most interest are 1) high monounsaturated fatty acids (MUFA) versus high polyunsaturated fatty acids (PUFA) at 30% and 37% Kcal total fat, 2) increased soluble fiber (concentrated Beta-glucan) at two dosage levels and different levels of total fat, 3) increased n -3 PUFA at 2 dosages and at different levels of total fat, 4) increased trans fatty acids at 2 levels and at different levels of total fat. The fifth experiment with an 11-week diet period evaluates a combination of components to yield optimal lipid response based on results of the first 4 experiments. Proposed ancillary outcomes include: LDL susceptibility to oxidation, antioxidant status, mononuclear cell cholesterol and postprandial lipids and insulin. The investigative group has expertise in the areas of nutrition, feeding studies, lipid biochemistry, dietetics, hemostasis, biostatistics, epidemiology and metabolism. Diets will be fed by the University of Minnesota general Clinical Research Center (CRC), which has long experience with production and feeding of well-controlled research diets. Each experiment will be conducted with 20 women, ages 30-64, recruited using well-established advertising and referral procedures. The interdisciplinary components of the study will be coordinated by a local Executive Committee which meets regularly and interfaces with the national Steering Committee, Day-to-day operations will be handled by functional managers who report directly to the principal investigator and the project coordinator. These studies are consistent with the long terms research program of the investigators to elucidate relationships between diet and disease.
