Individual Differences in Hyperlipidemia and Vitamin E Status in Response to Chronic Alcohol Self-Administration in Cynomolgus Monkeys

Background: Chronic ethanol self-administration induces oxidative stress and exacerbates lipid peroxidation. α-Tocopherol is a potent lipid antioxidant and vitamin that is dependent upon lipoprotein transport for tissue delivery. Methods: To evaluate the extent to which vitamin E status is deranged by excessive alcohol consumption, monkeys voluntarily drinking ethanol (1.36 to 3.98g/kg/d for 19months, n=11) were compared with nondrinkers (n=5, control). Results: Three alcohol-drinking animals developed hyperlipidemia with plasma triglyceride levels (1.8±0.9mM) double those of normolipidemic (NL) drinkers (0.6±0.2) and controls (0.6±0.3, p<0.05); elevated plasma cholesterol (3.6±0.5mM) compared with NL drinkers (2.3±0.2, p<0.05) and controls (2.9±0.3); and lower plasma α-tocopherol per triglycerides (14±6mmol/mol) than controls (27±8) and NL drinkers (23±6, p<0.05). Hyperlipidemic monkey liver α-tocopherol (47±15nmol/g) was lower than NL drinkers (65±13) and controls (70±15, p=0.080), as was adipose α-tocopherol (84±37nmol/g) compared with controls (224±118) and NL drinkers (285±234, p<0.05). Plasma apolipoprotein (apo) CIII increased compared to baseline at both 12 and 19months in the normolipidemic (p=0.0016 and p=0.0028, respectively) and in the hyperlipidemic drinkers (p<0.05 and p<0.05, respectively). Plasma apo H concentrations at 19months were elevated hyperlipidemics (p<0.05) relative to concentrations in control animals. C-reactive protein (CRP), a marker of inflammation, was increased compared to baseline at both the 12- and 19-month time points in the normolipidemic (p=0.005 and p=0.0153, respectively) and hyperlipidemic drinkers (p=0.016 and p=0.0201, respectively). Conclusion: A subset of alcohol-drinking monkeys showed a predisposition to alcohol-induced hyperlipidemia. The defect in lipid metabolism resulted in lower plasma α-tocopherol per triglycerides and depleted adipose tissue α-tocopherol, and thus decreased vitamin E status.