Hyperhomocysteinemia in chronic alcoholism: relations to folic acid and vitamins B(6) and B(12) status

Abstract

The objective of this review is to present and discuss the current perspectives of homocysteine and one carbon metabolism in chronic alcoholism. Chronic alcoholics frequently suffer from specific micronutrient deficiencies, including 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 intersection 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, cystathionine-beta-synthase. Due to these relationships, nutritional deficiency of one of these vitamins, as a consequence of chronic alcohol intake, could lead to metabolic disruption and potentially to hyperhomocysteinemia. Consistent with an interference of alcohol in these metabolic pathways, a previous study performed in chronic alcoholics in whom hyperhomocysteinemia was observed along with disturbed vitamin status, DNA hypomethylation in peripheral lymphocytes was demonstrated as well. Because all these alterations were 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.