Alcohol's influence on plasma lipoproteins: a nonhuman primate model

Ethanol (EtOH) is a common component of the American diet which can contribute 5-18% of the total calories consumed by nonalcoholics and 35-50% of the total energy intake of alcoholics. Moderate alcohol consumption may protect against coronary heart disease (CED) while excessive drinking has adverse cardiovascular effects. The underlying basis of the alcohol-heart disease relationship may involve the ability of this drug to modify the level of circulating lipoproteins, particularly atherogenic low density lipoproteins (LDL) and antiatherogenic high density lipoproteins (HDL). In an effort to overcome a number of dietary-lifestyle variables and intake reporting errors associated with human studies, an animal model (atherosclerosis-susceptible male squirrel monkeys) was developed which enabled investigators to deliver quantitative doses of EtOH (vodka) (substituted isocalorically for carbohydrate) to monkeys as part of a chemically defined liquid diet. The first part of this review describes experiments which evaluate the effect of alcohol dose (low, moderate, high), drinking period (acute vs. chronic), and drinking pattern (regular vs. binge) on lipoprotein composition, while the second part discusses the enzymatic/metabolic basis for the observed lipoprotein alterations. The concluding section proposes that high dose (24% calories) alcohol may induce alterations in liver membrane and/or lipoprotein receptors/binding sites which may slow the clearance of lipoproteins from the circulation and thus initiate a sequence of metabolic changes leading to elevations in LDL and HDL lipid and protein components. Enhanced de novo synthesis in response to high EtOH intake may further increase the plasma HDL concentration. An extended residence time in circulation of HDL particles may be beneficial in sequestering peripheral cholesterol for eventual excretion via the reverse cholesterol transport pathway given that HDL hepatic lipid degradation and sterol/bile acid excretion remain active in animals fed the high alcohol regimen. On the other hand, a sustained elevation in plasma LDL would promote the progression of atherosclerosis. The close similarity between humans and squirrels monkeys in their lipoprotein response to alcohol emphasizes the pathophysiological relevance of this animal model, and the valuable role they may play in providing a greater understanding of the relationship between ethanol, lipoproteins, and CHD.