Mechanisms of Ethanol-Drug-Nutrition Interactions

Abstract

Mechanisms of the toxicologic manifestations of ethanol abuse are reviewed. Hepatotoxicity of ethanol results from alcohol dehydrogenase-mediated excessive hepatic generation of nicotinamide adenine dinucleotide and acetaldehyde. It is now recognized that acetaldehyde is also produced by an accessory (but inducible) pathway, the microsomal ethanol-oxidizing system, which involves a specific cytochrome P450. It generates oxygen radicals and activates many xenobiotics to toxic metabolites, thereby explaining the increased vulnerability of heavy drinkers to industrial solvents, anesthetics, commonly used drugs, over-the-counter medications and carcinogens. The contribution of gastric alcohol dehydrogenase to the first pass metabolism of ethanol and alcohol-drug interactions is now recognized. Alcohol also alters the degradation of key nutrients, thereby promoting deficiencies as well as toxic interactions with vitamin A and β-carotene. Conversely, nutritional deficits may affect the toxicity of ethanol and acetaldehyde, as illustrated by the depletion in glutathione, ameliorated by S-adenosyl-L-methionine. Other supernutrients include polyenylphosphatidylcholine, shown to correct the alcohol-induced hepatic phosphatidylcholine depletion and to prevent alcoholic cirrhosis in non-human primates. Thus, a better understanding of the pathology induced by ethanol has now generated improved prospects for therapy.

KEY WORDS:

• ethanol
• alcohol dehydrogenase
• acetaldehyde
• cytochrome P450
• gastric
• alcohol-drug
• Vitamin A