Metabolic consequences of alcohol ingestion.

Many of the pathophysiological effects of alcohol ingestion relate to the pathways of ethanol metabolism. However, some of the acute and chronic effects of ethanol use are also attributable to the direct effects of ethanol, e.g. on membrane fluidity. Oxidation of ethanol to acetaldehyde is catalysed by alcohol dehydrogenase (ADH). There are at least six classes of ADH, some of which show inter-individual variation, i.e. genetic polymorphism, that influences the rate of ethanol oxidation. A consequence of ethanol oxidation is an increase in the NADH/NAD redox potential within the cytosol and mitochondria with subsequent alteration in several tissue metabolites. The popular hypothesis that most, if not all, of the consequences of chronic alcohol ingestion can be explained by these redox changes is still unproven. This should be considered in the context that most metabolic pathways of the liver are affected by alcohol, as are several endocrine axes in the whole body. In fact most, if not all, tissues and organs are deleteriously affected by chronic ingestion. Acetaldehyde, the product of ethanol oxidation, is chemically highly reactive, toxic and immunogenic. However, the concentrations achieved in vivo usually fall short of those used to produce these toxic effects in experimental situations. Oxidation of acetaldehyde is also coupled to redox changes, although primarily affecting the intra-mitochondrial redox. In addition, further oxidative pathways of ethanol metabolism can lead to the formation of fatty acid ethyl esters, hydroxyethyl free radicals and reactive oxygen species via the ethanol-specific cytochrome P450-2E1 system. There is no conclusive evidence that nutrient supplementation has beneficial effects on overall ethanol-mediated tissue damage.