[Dietary treatment of hyperlipoproteinemia. Reduction of atherogenic lipid fractions in normal subjects].
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Biomedical subjects
Publications and source records attributed to P Weisweiler.
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This study was designed to determine the effects of polyunsaturated fats and of reducing intake of total fat on serum lipids, lipoproteins, and apolipoproteins. Twenty-two normolipidemic women living in a nunnery were given a reference diet (fat/carbohydrate 42/46% of energy, P/S ratio 0.16), a polyunsaturated diet (42/46%, P/S 1,0), and a low-fat, polyunsaturated diet (32/56%, P/S 1.0) for 6 weeks each. Serum and lipoprotein lipids were determined by standard procedures, apolipoproteins either by laser immunonephelometry or by rocket immunoelectrophoresis. Consumption of the polyunsaturated diet decreased cholesterol and apolipoprotein B levels in VLDL (-33.1% and -23.8%) and in LDL (-13.5% and -8.8%) without affecting HDL. Consumption of the low-fat, polyunsaturated diet resulted in a reincrease of VLDL triglycerides, but not of VLDL cholesterol. Concentration of VLDL apolipoprotein B further fell (-41.6%) and that of apolipoprotein E decreased (-25.9%), resulting in an increased VLDL lipid/apolipoprotein mass ratio. This study indicates that responses to therapeutic polyunsaturated diet are lowered levels of VLDL and LDL, but unchanged levels of HDL. Additional restriction of dietary fat intake alters the VLDL composition with a decrement in apolipoprotein E enriched VLDL particles.
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The effects on serum lipoproteins were studied in 8 patients with familial heterozygous hypercholesterolemia and 9 patients with familial combined hyperlipidemia during an 8-week treatment with fenofibrate. VLDL, IDL, LDL and HDL were isolated by ultracentrifugation and precipitation. Lipids and apolipoproteins A-I and B were determined by enzymatic and immunonephelometric techniques, respectively. In hypercholesterolemia, administration of fenofibrate resulted in decreases of VLDL, IDL, and LDL (cholesterol -58.3%, -28.6%, and -24.4%), while, in combined hyperlipidemia, treatment with the drug lowered VLDL and IDL (-33.3% and -42.9%). HDL cholesterol and apolipoprotein A-I increased only in hypercholesterolemia (+22.9% and +6.9%).
A laser immunonephelometric procedure for the determination of human apolipoproteins A-I, B, and E in serum and lipoproteins was developed. Coefficients of variation were 2.3%-3.4% within-run, 4.7%-4.9% between-run. Serum apolipoprotein A-I values were similar in normal and hyperlipoproteinaemic subjects with a correlation coefficient of r = 0.585 to HDL-cholesterol levels. LDL-apolipoprotein B values were highly (r = 0.935), VLDL-apolipoprotein B values less strongly (r = 0.472) correlated to the corresponding cholesterol levels. Serum apolipoprotein E concentrations were distinctly elevated in Type III and not correlated to cholesterol values.
We studied the effect on the serum LCAT activity and apolipoproteins in ten subjects with primary hypercholesterolemia after treatment with beta-sitosterol. The 2-month administration of beta-sitosterol resulted in an increase of the fractional as well as of the molar esterification rate of the LCAT. These alterations were associated with a decrease of the levels of total, esterified, and unesterified cholesterol, whereas the levels of HDL-cholesterol and the apolipoproteins A-I and B were not affected. We conclude that beta-sitosterol primarily lowers cholesterol-rich lipoproteins with a lower density range than LDL via an accelerated esterification rate of the LCAT enzyme.
Since VLDL and LDL are involved in atherogenesis, their response to dietary modification was studied in 15 normal male prisoners. A 3-month reference diet (P/S ratio 0.3, daily cholesterol intake 370 mg) was compared with a modified fat diet (P/S 1.0, 250 mg) given for further 3 months. The decrement in serum cholesterol by 32 mg/dl reflected a decrease in VLDL and LDL. It was associated with a decrease in serum apolipoprotein B by 16 mg/dl and in serum apolipoprotein E by 1.2 mg/dl. The decrement in VLDL cholesterol was paralleled by a lowered VLDL apolipoprotein E content. Serum and VLDL triglycerides, HDL cholesterol and the serum apolipoproteins A-I and A-II did not change significantly. One beneficial result of a conventional dietary regimen is lowered LDL with unaffected HDL. Another effect is the apparent modification of VLDL with a decrement of cholesterol and apolipoprotein E-enriched particles.
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A laser immunonephelometric procedure for the determination of apolipoprotein E in human serum and lipoprotein fractions was developed. Coefficients of variation were 2.3% within-run, 4.7% between-run. The distribution of apolipoprotein E in various lipoprotein fractions revealed a higher proportion of apolipoprotein E in VLDL in hypertriglyceridaemic subjects (especially marked in Type III patients) than in normal subjects. Laser immunonephelometry appears suitable for the routine measurement of apolipoprotein E.
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Human prolipoprotein E is implicated in the transport of serum cholesterol and the binding of lipoproteins to cell receptors. Further investigations on this apolipoprotein would be facilitated by improved purification methods. We prepared human apo E by the combination of high performance gel filtration and chromatofocusing from serum very low density lipoproteins. Chromatofocusing was performed with a pH gradient from 7 to 4. Apo E contained all isoforms, but was homogeneous in SDS-polyacrylamide gel electrophoresis and in double immunodiffusion against a monospecific antiserum. The reported purification method allows a rapid and simple preparation of large amounts of apo E.
To evaluate possible influences of dietary intervention on the composition of very low-density lipoproteins (VLDL), ten subjects with Type 2 (non-insulin dependent) diabetes mellitus received a hypocaloric regimen. Fifteen healthy subjects served as controls. Ultracentrifuged VLDL were analysed as cholesterol, triglycerides, apolipoprotein B (apo B), and the soluble apolipoproteins C and E (polyacrylamide gel electrophoresis in urea and densitometry) before the study, after 2 weeks and then after 3 months. Compared with the control subjects, the content of cholesterol and apo E in the VLDL was elevated in the diabetic subjects, while the area ratio of apo C-II to apo C-III1 was lowered. After diet the reduction in VLDL was accompanied by compositional changes: a decrease of the cholesterol/triglyceride ratio and of the apo E/apo C area ratio. The apo C-II/apo C-III1 area ratio remained unaffected. We conclude that one beneficial effect of therapeutic intervention in diabetes may lie in lowering the level of possibly atherogenic VLDL-components.
The effects of a combined therapy, composed of a cholesterol-lowering diet, cholestyramine (16 g/day) and apple pectin (12 g/day), were studied on serum lipoproteins in 6 men with familial hypercholesterolemia. All subjects were treated with diet alone, diet plus cholestyramine and diet plus cholestyramine and pectin for at least 8 weeks on each regimen. In these severely hypercholesterolemic subjects the combined treatment with diet plus cholestyramine and pectin lowered serum cholesterol by 31% and LDL-cholesterol by 35% corresponding to a 19% and 22% further decrease respectively relative to diet plus cholestyramine. We conclude that the addition of the well-tolerated natural cholesterol-lowering product is valuable in the treatment of familial hypercholesterolemia.
Since diets containing a high P/S ratio have been reported to have detrimental effects on HDL, the effect of a moderately modified fat diet (P/S ratio 1.0, cholesterol content 250 mg/day) was investigated in 30 healthy male volunteers, divided into 2 groups. They were either given a modified fat diet or an isocaloric control diet (P/S ratio 0.3, cholesterol content 370 mg/day) for 3 months each in a cross-over design. After 3 months of the polyunsaturated fat diet LDL cholesterol was significantly lowered by 19 and 13%, respectively, in both groups. This effect was already apparent after 4 weeks. Apo A-I and cholesterol in serum and the subfractions HDL2 and HDL3 remained unchanged. Consequently, the ratio LDL/HDL cholesterol was decreased by this diet. Dietary adherence was good according to the typical changes of the linoleic acid content in serum cholesteryl esters, to the dietary recalls and to the constant body weight. We conclude that a moderately modified fat diet supplied from mixed general food is acceptable for longer periods, effectively lowers LDL cholesterol, even in normolipoproteinemic subjects, and has no detrimental effects on HDL.
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