This proposal addresses important questions about the effects of dietary fatty acids on plasma lipids and measures of hemostasis that can be most effectively answered utilizing a multicenter study design. Experiments are proposed for a Penn State Field Center that are compatible with the Cooperative Diet Studies Project. Our guiding hypothesis is that the long- chain saturated fatty acids (SFA) are atherogenic (with the exception of stearic acid) by virtue of their effects on two major risk factors for coronary heart disease, blood lipids and thrombosis. We propose to study young men and women and middle-aged men and women and children (families) to gain a better understanding of the effects of age, gender, genetics and baseline cholesterol level on the plasma cholesterol response to dietary fatty acids and cholesterol. Utilizing a randomized, double-blinded, cross-over study design subjects will be fed carefully formulated experimental diets that provide 30% of calories from fat. Our proposed experiments will address the following key questions: 1) What are the relative hypercholesterolemic effects of the major long-chain SFA (myristic, palmitic and stearic acid)? Is the response potentiated by dietary cholesterol (69 mg/day vs.300 mg/day)? 2) What are the relative cholesterolemic effects of stearic versus linoleic acid and linoleic versus oleic acid? 3) What are the effects of trans fatty acids on plasma lipids and Lp(a) levels? and 4) How do fatty acids affect hemostasis? To answer these questions we propose to conduct four feeding studies. Whole food diets that contain special fat-modified meat products will enable us to study the interactive effects of dietary fatty acids and cholesterol. Our primary lipid endpoints are total cholesterol, triglycerides, LDL-C and HDL-C. Measures of hemostasis include fibrinogen, factor VII activity, plasminogen and PAI-1. Urinary 6-keto-PGF1 alpha and TBX2 also will be quantified to examine dietary fatty acid effects on platelet function. In addition to the major studies described, four ancillary studies are proposed to increase our understanding of the effects of dietary fatty acids on lipoprotein metabolism and immune function. Our experimental design enables us also to study dietary assessment methodologies.
