Mechanisms
Heavy alcohol drinkers with sky-high HDL show sharply reduced CETP activity and mass, mimicking genetic deficiency (Metabolism 1992)
Original title: Polydisperse low-density lipoproteins in hyperalphalipoproteinemic chronic alcohol drinkers in association with marked reduction of cholesteryl ester transfer protein activity
Eight male chronic heavy alcohol drinkers with marked hyperalphalipoproteinemia, HDL cholesterol from 2.67 to 3.58 mmol/L, were studied despite three having coronary heart disease and seven having corneal arcus. CETP activity was reduced in every subject compared with controls (7.3 plus or minus 4.2%/10 microL/18h versus 20.5 plus or minus 2.4%/10 microL/18h, P less than .001), and CETP mass was likewise markedly reduced. On gradient gel electrophoresis, four subjects with severely low CETP activity (under 25% of control) had polydisperse LDL resembling genetic CETP deficiency, while the other four with roughly half-normal CETP activity had homogeneous but smaller LDL, and HDL particle size was larger than normal in all subjects. After alcohol cessation, HDL cholesterol fell and LDL became more homogeneous and normal-sized in parallel with rising CETP activity, showing heavy drinking suppresses CETP and reproduces a lipoprotein phenotype resembling genetic CETP deficiency.
Original abstract
Long-term heavy alcohol intake is well known to increase serum high-density lipoprotein (HDL) cholesterol concentrations. Epidemiologic studies have shown that the protective effect of alcohol intake against coronary heart disease (CHD) is observed in moderate alcohol drinkers, but not in heavy ones. To clarify whether heavy alcohol intake may cause abnormalities in lipoprotein metabolism, we analyzed the plasma lipoproteins in eight male chronic heavy alcohol drinkers with marked hyperalphalipoproteinemia. Although their serum HDL cholesterol levels were remarkably high, ranging from 2.67 to 3.58 mmol/L, three patients had CHD and corneal arcus was present in seven patients. Cholesteryl ester transfer protein (CETP) activity was reduced in all subjects (7.3% +/- 4.2%/10 microL/18 h in alcohol drinkers v 20.5% +/- 2.4%/10 microL/18 h in control; mean +/- SD, P < .001). The CETP mass levels were also markedly reduced in these subjects. The analysis of low-density lipoprotein (LDL) on nondenaturing polyacrylamide gradient gel electrophoresis revealed that four subjects with severely low CETP activity (< 25% of control) had polydisperse LDLs, similar to those observed in genetic CETP deficiency. The other four subjects with approximately half the normal CETP activity had homogeneous but smaller-sized LDLs, as compared with control subjects. Particle size of HDL was larger than that of normal control HDL in all subjects. After cessation of alcohol intake, plasma HDL cholesterol levels were decreased and LDLs became more homogeneous and normal in size, in parallel with elevation of CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.