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 [Chol] increases LDL [low-density lipoprotein] production and decreases LDL receptor-related LDL clearance, resulting in elevations in LDL Chol levels of .apprx. 30 mg/dl. To assess the effects of high fat and high Chol diets on the lipoproteins of individuals with diminished LDL receptors, 3 kinds of diets, including those high in Chol, were fed to 4 patients with familial hypercholesterolemia, in the expectation that diet effects on [apoprotein] apoB- or apoE-containing lipoproteins would be exaggerated. The basal diet consisted of 15% protein, 30% fat, 55% carbohydrate, 300 mg/d Chol, P/S ratio [polyunsaturated to saturated fatty acids ratio] 0.4; the high fat diet was identical except that fat calories were 55% and carbohydrate 30%; the high fat-high Chol diet was identical with the high fat diet except .apprx. 750 or .apprx. 1,500 mg/d of Chol were added. Each diet was eaten for 5 wk at home and for the 6th wk at the general Clinical Research Center [USA]. Fasting (12-14 h) plasmas were collected every 2 wk for lipoprotein-lipid and apoprotein quantitation. At the end of each period, fasting and 4-h postprandial samples were analyzed also by zonal ultracentrifugation and gel permeation chromatography. On analysis of fasting samples on the fat + Chol diet, measures of the levels of VLDL [very-low-density lipoprotein] (i.e., 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 [high-density lipoprotein] HDL2 and HDLc rose. Compositions of VLDL were altered, i.e., mass percentage of triglycerides fell and Chol rose. Zonal effluent profiles of VLDL, LDL, HDL2 and HDL3 were not altered, nor were gel chromatographic elution patterns of Chol, triglycerides, apoB, apoA-I, and apoE, suggesting that the sizes and/or densities of lipoproteins were not altered. 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. Having diminished numbers of LDL receptors did not affect the ability 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.