People with liver defects often cannot synthesize SAMe in their bodies, and some preliminary studies suggest that taking SAMe may have some therapeutic benefits for chronic liver disorder caused by medications or alcoholism. A study of 123 men and women with alcoholic liver cirrhosis (liver failure) found that those who consumes SAMe for 2 years improved liver health and delayed the need for liver transplants better than placebo. Other studies show that SAMe may support normalize levels of liver enzymes in people with liver defects. These studies have been small and of short duration. Larger and longer studies are needed to confirm these findings.
The potential therapeutic benefit of SAMe for liver disease stems from several important aspects of SAMe metabolism. In mammals, as much as 80% of the methionine in the liver is converted into SAMe (23). Hepatic glutathione, which is dependent on methionine and SAMe metabolism, is one of the principal antioxidants involved in hepatic detoxification. Studies have shown that abnormal SAMe synthesis is associated with chronic liver disease, regardless of its etiology. Early studies indicated that patients with liver disease are unable to metabolize methionine, resulting in elevated blood concentrations (67). Subsequent studies in patients with liver disease showed that the defect resulted from decreased activity of a liver-specific isoenzyme, MAT I/III; this defect effectively blocks the conversion of methionine to SAMe (68). Several well-designed experimental studies indicated that MAT I/III is regulated by cellular concentrations of both nitric oxide and glutathione. Thus, increased nitric oxide concentrations and decreased glutathione concentrations were shown to inhibit MAT I/III via mechanisms involving increased S-nitrosylation and free radical damage to the enzyme protein (69, 70). Experimental studies and clinical trials showed that parenteral and oral SAMe administration can increase glutathione concentrations in red blood cells (71) and in hepatic tissue (72, 73) and can effectively replenish depleted glutathione pools in patients with liver disease. The literature on the clinical potential of therapeutic benefits of SAMe in the for liver conditions (including cholestasis, hepatitis, and cirrhosis) has been the subject of several review articles (9–11, 74, 75).