Effects of high cholesterol high fat diet on plasma lipoproteins in familial hypercholesterolemia

Heterozygous individuals with familial hypercholesterolemia possess about half of the normal numbers of functioning receptors on their cells. This is thought to be responsible for their hypercholesterolemia. In normals, dietary cholesterol increases LDL production and decreases LDL receptor-related LDL clearance, resulting in elevations in LDL cholesterol levels of ∼30 mg/dL. To assess the effects of high fat and high cholesterol diets on the lipoproteins of individuals with diminished LDL receptors, three kinds of diets, including ones high in cholesterol, were fed to four patients with familial hypercholesterolemia, in the expectation that diet effects on apoB- or apoE-containing lipoproteins would be exaggerated. The basal diet consisted of 15% protein, 30% fat, 55% carbohydrate, 300 mg/d cholesterol, PS ratio 0.4; the high fat diet was identical except that fat calories were 55% and carbohydrate 30%; the high fat-high cholesterol diet was identical with the high fat diet except ∼750 or ∼1,500 mg/d of cholesterol were added. Each diet was eaten for five weeks at home and for the sixth week at the general Clinical Research Center. Fasting (12–14 hours) plasmas were collected every two weeks for lipoprotein-lipid and apoprotein quantitation. At the end of each period, fasting and 4-hour postprandial samples were analyzed also by zonal ultracentrifugation and gel permeation chromatography. The significant results were as follows: (1) on analysis of fasting samples on the fat + Chol diet, measures of the levels of VLDL (ie, VLDL lipids, VLDL protein on zonal ultracentrifugation, VLDL-associated lipids, and apoE on chromatography) fell; measures of LDL were not consistently changed; and measures of HDL2 and HDLc rose. Compositions of VLDL were altered, ie, mass % of triglycerides fell and cholesterol rose. Zonal effluent profiles of VLDL, LDL, HDL2, and HDL3 were not altered, nor were gel chromatographic elution patterns of cholesterol, triglycerides, apoB, apoA-I, and apoE, suggesting that the sizes and/or densities of lipoproteins were not altered. Therefore, the numbers of VLDL particles must have fallen and the numbers of HDL2 and HDLc must have risen. The nature and magnitude of the changes fell within the range of changes previously observed in normolipidemic subjects. The data indicate that having diminished numbers of LDL receptors did not affect the abilities of these patients to resist diet-induced qualitative or quantitative alterations of their plasma lipoproteins. Clearly other adaptive mechanisms can compensate for the diminished numbers of LDL receptors.