title: Folate, alcohol, and liver disease.
abstract: Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of ALD with particular focus on ethanol-induced alterations in methionine metabolism, which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of ALD based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions.
authors.affiliation: Department of Internal Medicine, University of California Davis, Davis, CA 95817, USA. valentina.medici@ucdmc.ucdavis.edu
authors.forename: Valentina
authors.initials: V
authors.lastname: Medici
authors.forename: Charles H
authors.initials: CH
authors.lastname: Halsted
mesh_terms: D000042:Absorption; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D005492:Folic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D005494:Folic Acid Deficiency / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D008715:Methionine / Q000378:metabolism; D008745:Methylation
chemical_list: D000975:Antioxidants; D000431:Ethanol; D005492:Folic Acid; D008715:Methionine