Despite a large body of work concerned with the role of diet and nutrient intake on plasma lipid concentrations, several important questions remain unaddressed. These uncertainties derive both from the lack of well-controlled, long-term diet trials carried out with adequate numbers of subjects, and from the inability of previous investigations to go beyond characterization of the major lipoprotein classes. In this proposed investigation we will combine carefully controlled, long-term diet studies in healthy subjects, with state of the art methods for isolating and characterizing lipoprotein subclasses. Methods to be used include a variety of ultracentrifugational techniques, immunoaffinity chromatography, and apolipoprotein epitope-mapping with monoclonal antibodies. In addition, we will determine the rates of production and catabolism of apolipoprotein B in very low density, intermediate density and low density lipoproteins, and of apolipoprotein AI in high density lipoproteins. We will carry out four studies whose aims are to: 1) study the effects of reduced fat diets that are enriched in either monounsaturated or polyunsaturated fats; 2) compare the effects of a diet containing 30% fat with those of a 20% fat diet; 3) compare the effects of 3 levels of dietary cholesterol (500 mg, 250 mg, and 100 mg per day); and 4) compare the effects of omega-3 and omega-6 fatty acid. These studies will be carried out with a parallel design, using both a cafeteria setting where 42 subjects can participate over a 7 month period for each study, and a General Clinical Research Center setting where 18 subjects can be studied under more rigorously controlled conditions. This parallel design approach will enable us to carry out both clinical trials and perform sophisticated laboratory measurements.
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