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 alcoholic liver disease 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 alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions.

Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

“…The folate cycle generates 5-MTHF from 5,10-methylenetetrahydrofolate in a reaction catalyzed by MTHF reductase. Alcohol is known to affect one-carbon metabolism by inhibiting folate-dependent homocysteine remethylation to methionine and AdoMet synthesis (43).…”

Diagnosis and treatment of nutritional deficiencies in alcoholic liver disease: Overview of available evidence and open issues

“…Folate deficiency typically characterizes ALD due to reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary excretion [23]. Herbert et al originally reported that 80% of the 70 chronic alcoholics admitted to a large US urban hospital showed low serum folate levels, with severe deficiency in 44% of them [24].…”

“…Both dietary and endogenous folate are involved in the hepatic methionine metabolism, which regulates homocysteine levels, antioxidant defences, DNA assembly, lipid export, and all epigenetic methylation reactions contributing to the gene expression regulation [23]. Dietary folates are metabolized in the liver and other tissues and the final metabolite is S-adenosylmethionine (SAM), which acts as a methyl donor for all the methylation reactions involving DNA, histones, and proteins [23].…”

“…Dietary folates are metabolized in the liver and other tissues and the final metabolite is S-adenosylmethionine (SAM), which acts as a methyl donor for all the methylation reactions involving DNA, histones, and proteins [23].…”

Principales daños sanitarios y sociales relacionados con el consumo de alcohol

“…Además, el alcohol empeora el pronóstico de las hepatopatías 83 . La aparición de fibrosis hepática podría estar mediada por cambios epigenéticos, alteraciones metabólicas (aumento de áci-dos grasos y estrés oxidativo que produce radicales libres, deficiencia de folato, etcé-tera), alteraciones de la respuesta inflamatoria (que podría ser inducida directamente por los metabolitos del etanol, principalmente acetaldehído, o por endotoxinas bacterianas del intestino) 7,[84][85][86] .…”