Abstract-Alcohol fed to rabbits in a liquid formula at 30% of calories increased plasma cholesterol by 36% in the absence of dietary cholesterol and by 40% in the presence of a 0.5% cholesterol diet. The increase was caused almost entirely by VLDL, IDL, and LDL. Cholesterol feeding decreased the fractional catabolic rate for VLDL and LDL apoprotein by 80% and 57%, respectively, and increased the production rate of VLDL and LDL apoprotein by 75% and 15%, respectively. Alcohol feeding had no effect on VLDL apoprotein production but increased LDL production rate by 55%. he effects of alcohol on cholesterol and lipoprotein metabolism have substantial public health implications. It is generally believed that moderate alcohol consumption reduces coronary heart disease risk because observational studies show that it is associated with elevated HDL cholesterol levels and decreased cardiovascular events. 1-3 However, alcohol has many biological actions, and adverse effects on lipid metabolism and cardiovascular disease risk are also well-known, especially in individuals with familial predisposition to hyperlipidemia. 4,5 Thus, the results of alcohol consumption are likely to reflect a balance that might be positive or negative in a given individual. Clearly, a more complete understanding of the interaction between alcohol and lipid metabolism is needed.To investigate the effects of alcohol under controlled dietary conditions, we previously reported the application of cholesterol-and alcohol-containing liquid formula diets that are palatable and allow good weight gain and gastrointestinal function in rabbits. 6,7 This work showed that instead of protecting against atherosclerosis, ethanol feeding at 20% to 30% of calories in the presence of dietary cholesterol (0.5% by weight) increased both plasma lipoproteins and aortic atherosclerotic lesions. In the presence of dietary cholesterol, plasma VLDL and LDL doubled when alcohol was substituted for carbohydrates at 30% of calories, and aortic arch cholesterol content increased fourfold. The current work was performed to investigate potential mechanism(s) responsible for these adverse alcohol-induced changes. The kinetics of VLDL and LDL were determined by tracer methods after varying periods of dietary treatment, and cholesterol absorption was measured at the end of the experiment. The results suggest that alcohol induced increased cholesterol absorption. As a result fractional catabolic rates for VLDL and LDL decreased and production of LDL increased. These changes probably account for the adverse effects of alcohol on lipoprotein metabolism and atherosclerosis in the cholesterol-fed rabbit. Methods Animals and DietForty female New Zealand White rabbits were housed individually during a 6-week study. The animals were divided into 4 groups at the beginning of the trial and fed liquid diets as previously described in detail. 7 All diets were isonitrogenous and isocaloric with alcohol replacing carbohydrate. The control diet (L) contained 18% fat and 56% carbohydrate and was f...