The National Cholesterol Education Program (NCEP) has recommended a diet (Step II) restricted in cholesterol (<200mg/day) and saturated fat (<7% of calories) for subjects with elevated plasma low density lipoprotein (LDL) cholesterol levels. Polyunsaturated fat intake is not to exceed 10% of calories, but the precise ratio of w6:w3 fatty acids has not been specified. In the previous grant cycle we have developed novel methodology to study apolipoprotein kinetics in the fed state using deuterated leucine, and have examined the long term effects (24 weeks) of a diet restricted i saturated fat (5% of calories) and cholesterol (60 mg/1000 calories), with 7% w6 fatty acids and 3% w3 fatty acids (mainly 20:5w3 and 22""""""""6w3) in 10 normal subjects on lipoproteins, blood pressure, and immune function. as compared to an average U.S. diet, the restricted diet decreased all lipoprotein fractions, decreased LDL cholesterol by 14% with enhanced LDL apoB-100 catabolism, decreased VLDL apoB-100 synthesis, increased LDL apoB- 100 catabolism, decreased VLDL apoB-100 synthesis, increased LDL apoB-100 synthesis, enhanced HDL apoA-I catabolism, and significantly decreased immune function (delayed hypersensitivity, lymphocyte proliferation, interleukin 1 production) as well as lowered blood pressure. We are now studying four normal subjects on a similar restricted diet except that 2% of calories are from w3 fatty acids, mainly 18:3w3. We now propose to study an additional 8 normal subjects, and if no adverse effects on immune function are noted, to study 12 subject with LDL cholesterol > 160 mg/dl and normal fasting triglyceride levels, and 12 subjects with LDL cholesterol values > 160 mg/dl, and triglycerides levels above the 90th percentile on a baseline diet for 6 weeks and a modified diet for 8 weeks. The proposed studies will: 1) allow us to develop an effective cholesterol lowering diet meeting NCEP Step II criteria that does not have adverse effects on immune response. 2) test the efficacy of this diet on lipid lowering in normal subject (n- 12) and in subjects with elevated LDL cholesterol levels (n=24); 3) assess apolipoprotein kinetics in the fed state in these subjects on a baseline diet and a diet restricted in cholesterol and saturated fat, in order to determine why LDL is elevated in some subjects and to examine the etiology of heterogeneity in response to diet in LDL lowering. 4) assess the effect of this diet on blood pressure.
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