Hyperhomocysteinemia in chronic alcoholism: Relations to folic acid and vitamins B-6 and B-12 status

The objective of this review is to present and discuss the current perspect ives of homocysteine and one carbon metabolism in chronic alcoholism. Chron ic alcoholics frequently suffer from specific micronutrient deficiencies, i ncluding vitamins involved in one carbon metabolism, i.e., folate, vitamin B-6 and vitamin B-12. The possible link between homocysteine and alcoholism stems from the fact that homocysteine metabolism is closely linked to the metabolism of these three vitamins. In fact, homocysteine stands at the int ersection of two pathways: methylation and transsulfuration. In methylation , homocysteine acquires a methyl group from N-5-methyltetrahydrofolate in a vitamin B-12 dependent reaction, whereas in the transsulfuration pathway, homocysteine condenses with serine to form cystathionine in an irreversible reaction catalyzed by the pyridoxal-5'-phosphate-containing enzyme, cystat hionine-beta-synthase. Due to these relationships, nutritional deficiency o f one of these vitamins, as a consequence of chronic alcohol intake, could lead to metabolic disruption and potentially to hyperhomocysteinemia. Consi stent with an interference of alcohol in these metabolic pathways, a previo us study performed in chronic alcoholics in whom hyperhomocysteinemia was o bserved along with disturbed vitamin status, DNA hypomethylation in periphe ral lymphocytes was demonstrated as well. Because all these alterations wer e observed in the absence of clinically overt disease, one might speculate whether these metabolic abnormalities could be involved in the pathogenesis of organic diseases associated to chronic alcoholism. Nutrition 2000;16:29 6-302. (C)Elsevier Science Inc. 2000.