S-adenosyl-L-methionine (SAM, or SAMe)

  • SAMe is an active compound made from methionine and adenosine triphosphate (ATP). It acts as a methyl donor in a variety of biochemical pathways. Methylation reactions are essential for the detoxification of harmful products of metabolism, and the synthesis of numerous physiological agents including neurotransmitters, cartilage, and glutathione.

  • The role of SAMe for depression, osteoarthritis, cholestasis of pregnancy and intrahepatic cholestasis associated with liver disease is well documented.

SAMe in liver protection :-

  • SAMe improves and normalizes liver function. In Europe, SAMe is used in the treatment of cirrhosis and liver damage caused by alcohol.

  • Through methylation, SAMe increases membrane fluidity, restoring several factors that promote bile flow.

  • Treatment with SAMe helps decrease serum bilirubin (pigment in the blood that can cause jaundice) in patients with elevated serum bilirubin level.

SAMe In Cholestasis :-

  • Another basic cellular activity of SAMe is its role as a methyl donor and enzyme activator in the transmethylation and transsulfuration reactions important for membrane structure and function. One of the important consequences of the failure of these functions is insufficiency of bile formation, a key aspect of many diseases of the liver, resulting in a pathologic state called cholestasis. SAMe opposes successfully many of the cholestatic states. SAMe improves both the pruritus and the biochemical indexes of cholestasis, such as serum bilirubin, alkaline phosphatase and – glutamyltransferase. It is noteworthy that in a prospective, multicenter, double-blind, placebo-controlled trial performed in 220 inpatients with chronic liver disease (chronic active hepatitis and cirrhosis, including primary biliary cirrhosis), serum markers of cholestasis and subjective symptoms (eg, pruritus and fatigue) significantly improved after SAMe treatment.8

SAMe in opposing fibrosis :-

  • The leading cause of morbidity and mortality in all major liver diseases is an inappropriately excessive healing process with uncontrolled scarring or fibrosis culminating in cirrhosis. SAMe was shown to be therapeutically useful in alleviating this process experimentally and for improving the outcome clinically.8

SAMe in alcoholic liver disorders :-

  • The most common liver disease for which SAMe has been shown to be useful therapeutically is alcoholic liver injury including cholestasis, and in the devastating consequences of excessive liver fibrosis (leading to cirrhosis).

  • S-Adenosyl-L-methionine (SAMe) exerts many key functions in the liver, including serving as a precursor for cysteine and glutathione the major physiologic defense mechanism against oxidative stress. SAMe is particularly important in opposing the toxicity of free oxygen radicals generated by various pathogens, including alcohol, which cause oxidative stress largely by the induction of cytochrome P4502E1 (CYP2E1) and by its metabolite acetaldehyde. SAMe also acts as the main methylating agent in the liver.8

  • SAMe in vivo is associated with beneficial effects on liver function and structure and resulted in a corresponding attenuation of ethanol-induced liver injury as shown by a less-striking glutathione depletion and lesser increases in plasma aspartate transaminase. SAME also shows hepatocyte mitochondrial protection. In rats, SAMe also decreased ethanol-induced fat accumulation. Thus, SAMe was shown to be useful for opposing the oxidative stress and the alcohol- induced liver injury.

  • Membrane alterations are common in alcoholic liver injury and are also associated with a decrease in phosphatidylcholine, the backbone of the membranes. SAMe increases phosphatidylcholine concentrations in the liver membranes by methylation reactions and thus protects hepatocytes from damages.

Racemethionine in Glutathione synthesis :-

  • Racemethionine is an essential amino acid in the synthesis and metabolism of other important substances like cysteine, s-adenosylmethionine (SAM or SAMe) and glutathione.

  • Abbreviations: THF: tetrahydrofolate; MS: methionine synthase; BHMT: betaine-homocysteine methyltransferase; MAT: methionine adenosyltransferase; SAM: S-adenosylmethionine; SAH S-adenosylhomocysteine; SAHH: SAH hydrolase; ADA: adenosine deaminase; AK: adenosine kinase; CBS: cystathionine beta synthase.