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A comprehensive assessment of lipoprotein compositional/metabolic response to incremental caloric ethanol (EtOH) doses ranging from low to moderate to high was undertaken using male squirrel monkeys. Control monkeys were maintained on a chemically defined, isocaloric liquid diet, while experimental primates wee fed increasing doses of alcohol (6, 12, 18, 24, 30, and 36% of energy) substituted isocalorically for carbohydrate at 3-month intervals. Liver function tests and plasma triglyceride were normal for all animals. Plasma cholesterol showed a transient increase at the 12% caloric dose that was attributed solely to an increase in high density lipoprotein (HDL). A more pronounced increase in plasma sterol, beginning at 24% and continuing to 36% EtOH, was the result of increments in both HDL and low density lipoprotein (LDL) cholesterol, although the contribution by the latter was substantial primarily at the 36% dose. Plasma apolipoprotein elevations (HDL apolipoprotein A-I, LDL apolipoprotein B) generally accompanied the lipoprotein lipid increases, although the first atherogenic response for LDL became manifest as a significant increase in apolipoprotein B at 18% EtOH calories. Postheparin plasma lipoprotein lipase was not affected by dietary alcohol, whereas hepatic triglyceride lipase activity showed significant increases at higher (24 and 36%) EtOH doses. Plasma lecithin-cholesterol acyltransferase activity was normal at the 6 and 12% EtOH doses, but exhibited a significant reduction beginning at 18% and continuing to 36% EtOH. Alterations in these key lipoprotein regulatory enzymes may represent the underlying metabolic basis for the observed changes in lipoprotein levels and our earlier findings of HDL2/HDL3 subfraction modifications. Results from our study indicate that in squirrel monkeys, moderate (12%) EtOH caloric intake favors an antiatherogenic lipoprotein profile (increases HDL, normal LDL levels, and lecithin-cholesterol acyltransferase activity), whereas higher doses (24-36%) produce both coronary-protective (increases HDL) and atherogenic (increases LDL) responses. Moreover, the 18% EtOH level represents an important transition dose which signals early adverse alterations in lipoprotein composition (increases apolipoprotein B) and metabolism (decreases lecithin-cholesterol acyltransferase).

The time course of lipoprotein changes during ethanol (EtOH) consumption followed by abstinence was examined in 3 groups of male squirrel monkeys: 1) controls fed isocaloric liquid diet; 2) low EtOH monkeys given liquid diet with vodka substituted isocalorically for carbohydrate at 12% of calories; and 3) high EtOH animals fed diet plus vodka at 24% of calories. After 2 weeks, high EtOH monkeys showed significant elevations in total plasma cholesterol which continued to increase at 4 weeks and then declined at 8 weeks. These elevations were the result of increases in both low density (LDL)- and high density lipoprotein (HDL)-cholesterol. Low EtOH monkeys had a modest increase in total cholesterol throughout 8 weeks which was attributed to increments in HDL-cholesterol alone. During abstinence, total, HDL- and LDL-cholesterol concentrations decreased rapidly in the high EtOH group and were similar to control values after 4 days. HDL-cholesterol showed a more gradual decline in animals fed 12% EtOH while LDL-cholesterol remained low and not significantly different from controls. Liver function tests were normal for all animals. Our results indicate that low-dose EtOH favors a coronary protective lipoprotein profile (increases HDL, decreases LDL) in squirrel monkeys while the higher alcohol regimen causes both favorable and unfavorable alterations in plasma lipids which quickly revert to control levels during abstinence.

Male squirrel monkeys were fed increasing caloric percentages (0, 12, 24, and 36%) of ethanol (ETOH) substituted isocalorically for carbohydrate as part of a chemically defined liquid diet to assess how alcohol dose modifies plasma lipoproteins and liver function. A separate group of primates was used to define the dose at which elevations in plasma apolipoprotein B first occurred and to measure plasma alcohol levels. ETOH caused a dose-related, linear increase in high density lipoprotein (HDL) cholesterol which was primarily the result of increments in coronary protective HDL2 cholesterol. HDL2 total mass (lipid + protein) followed the pattern of HDL2 cholesterol. Animals fed the 12% regimen had plasma ETOH levels of approximately 49 mg/dl, the lowest low density lipoprotein (LDL) cholesterol, and the highest HDL2/HDL3 cholesterol ratio. Significant elevations in apolipoprotein B first appeared at 18% ETOH while higher doses (24 and 36%) caused increases in LDL cholesterol and HDL3, reduced HDL2/HDL3 ratios, and plasma alcohol levels of 142 and 202 mg/dl, respectively. Liver function tests were normal for all animals. Our results indicate that while a moderate ETOH caloric intake (12%) produces an antiatherogenic lipoprotein profile (decreases LDL/HDL, increases HDL2/HDL3), any coronary protection afforded by continued increases in HDL2 at higher doses may be attenuated by concurrent atherogenic alterations (increases LDL cholesterol, increases apolipoprotein B).