Effects of alcohol on folate metabolism: implications for carcinogenesis.
Epidemiologic observations implicate excess ethanol ingestion as well as low dietary folate intake as risk factors for several cancers. Moreover, the epidemiologic observations support the concept of a synergistic effect between these two factors. Such a relation is biologically plausible because ethanol impedes the bioavailability of dietary folate and is known to inhibit select folate-dependent biochemical reactions. For example, alcohol ingestion in animals is known to inhibit folate-mediated methionine synthesis and thereby may interrupt critical methylation processes that are mediated by the activated form of methionine that provides substrate for biologic methylation, S-adenosylmethionine. Consistent with this observed inhibition of methionine synthesis is the observation that chronic alcohol ingestion in laboratory animals is known to produce hypomethylation of DNA in the colonic mucosa, a constant feature of early colorectal neoplasia. Inhibition of methionine synthase also creates a "methylfolate trap," analogous to what occurs in vitamin B12 deficiency. In addition, some evidence indicates that alcohol may redirect the utilization of folate toward serine synthesis and thereby may interfere with a critical function of methylenetetrahydrofolate, thymidine synthesis. Although a mechanistic link between alcohol and impaired folate metabolism in the genesis of cancer is still not definitively established, such a link should be pursued in future studies because of the intimate metabolic relation between alcohol and folate metabolism.
Mason
Joel B
JB
Vitamins and Carcinogenesis Laboratory, U.S.D.A. Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. joel.mason@tufts.edu
Choi
Sang-Woon
SW
D000818:Animals; D001622:Betaine / Q000494:pharmacology; D001682:Biological Availability; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000494:pharmacology*; D002794:Choline / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced*
D002492:Central Nervous System Depressants; D000431:Ethanol; D001622:Betaine; D005492:Folic Acid; D002794:Choline