Role of S-adenosyl-l-methionine in the treatment of alcoholic liver disease:☆

Abstract 

The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on “Role of S-Adenosyl-l-Methionine (SAMe) in the Treatment of Alcoholic Liver Disease” in Bethesda, Maryland, September 2001. Alcoholic liver disease (ALD) is a major cause of illness and death in the United States. Oxidant stress plays a key role in pathogenesis of liver disease. S-Adenosyl-l-methionine, a dietary supplement, is the methyl donor for biochemical methylation reactions and a precursor of glutathione, the main hepatocellular antioxidant. S-Adenosyl-l-methionine has been shown to attenuate liver injury caused by alcohol and other hepatotoxins in some animal models. Understanding the mechanisms by which SAMe attenuates liver injury caused by alcohol may provide useful information for full-scale human clinical trials. For this symposium, seven speakers were invited to address the following issues: (1) impaired methionine metabolism in alcoholic liver injury; (2) regulation of liver function by SAMe; (3) folate deficiency, methionine metabolism, and alcoholic liver injury; (4) attenuating effect of SAMe on ALD in experimental animals; (5) SAMe and mitochondrial glutathione depletion in ALD; (6) SAMe and cytokine production in liver injury; and (7) role of SAMe in the prevention of hepatocarcinogenesis. The presentations of this symposium support the suggestion that SAMe may have potential to treat ALD by (1) acting as a precursor of antioxidant glutathione, (2) repairing mitochondrial glutathione transport system, (3) attenuating toxic effects of proinflammatory cytokines, and (4) increasing DNA methylation. Further studies are required to evaluate the safety and effectiveness of SAMe treatment.

Keywords:  S-adenosyl-l-methionine (SAMe), Alcoholic liver disease (ALD), Oxidant stress, Methylation, Glutathione