Herman Award Lecture, 1993: a personal perspective on alcohol, nutrition, and the liver.
Alcohol causes primary malnutrition by displacing nutrients in the diet and secondary malnutrition via malabsorption and cellular injury through direct cytotoxicity. Hepatotoxicity results from metabolic disturbances associated with the oxidation of ethanol via liver alcohol dehydrogenase (ADH) and the redox changes produced by the generated NADH (the reduced form of nicotinamide adenine dinucleotide), which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Ethanol is also oxidized in liver microsomes by an ethanol-inducible cytochrome P450, which contributes to the alcoholic's tolerance and his increased vulnerability to the toxicity of industrial solvents, anesthetics, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and retinoids. Increased acetaldehyde generation, with formation of protein adducts, results in antibody production, enzyme inactivation, decreased DNA repair, impaired utilization of oxygen, glutathione depletion, free radical-mediated toxicity, lipid peroxidation, and increased collagen synthesis. Therapy may eventually improve with the use of supernutrients such as S-adenosyl-L-methionine, which replenishes glutathione, restores methylation, and attenuates liver injury, as well as dilinoleoylphosphatidylcholine, which prevents cirrhosis.
Lieber
C S
CS
Section of Liver Disease and Nutrition, Bronx Veterans' Affairs Medical Center, New York 10468.
D000435:Alcoholic Intoxication / Q000150:complications; D001363:Awards and Prizes; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008108:Liver Diseases, Alcoholic / Q000209:etiology; D009748:Nutrition Disorders / Q000139:chemically induced / Q000188:drug therapy; D009747:Nutritional Physiological Phenomena; D010713:Phosphatidylcholines / Q000627:therapeutic use; D012436:S-Adenosylmethionine / Q000627:therapeutic use; D012955:Societies, Medical
D010713:Phosphatidylcholines; C029449:polyene phosphatidylcholine; D000431:Ethanol; D012436:S-Adenosylmethionine