Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium

Abstract

This report is a summary of a symposium on the role of S-adenosylmethionine (SAM), betaine, and folate in the treatment of alcoholic liver disease (ALD), which was organized by the National Institute on Alcohol Abuse and Alcoholism in collaboration with the Office of Dietary Supplements and the National Center for Complementary and Alternative Medicine of the National Institutes of Health (Bethesda, MD) and held on 3 October 2005. SAM supplementation may attenuate ALD by decreasing oxidative stress through the up-regulation of glutathione synthesis, reducing inflammation via the down-regulation of tumor necrosis factor-alpha and the up-regulation of interleukin-10 synthesis, increasing the ratio of SAM to S-adenosylhomocysteine (SAH), and inhibiting the apoptosis of normal hepatocytes and stimulating the apoptosis of liver cancer cells. Folate deficiency may accelerate or promote ALD by increasing hepatic homocysteine and SAH concentrations; decreasing hepatic SAM and glutathione concentrations and the SAM-SAH ratio; increasing cytochrome P4502E1 activation and lipid peroxidation; up-regulating endoplasmic reticulum stress markers, including sterol regulatory element-binding protein-1, and proapoptotic gene caspase-12; and decreasing global DNA methylation. Betaine may attenuate ALD by increasing the synthesis of SAM and, eventually, glutathione, decreasing the hepatic concentrations of homocysteine and SAH, and increasing the SAM-SAH ratio, which can trigger a cascade of events that lead to the activation of phosphatidylethanolamine methyltransferase, increased phosphatidylcholine synthesis, and formation of VLDL for the export of triacylglycerol from the liver to the circulation. Additionally, decreased concentrations of homocysteine can down-regulate endoplasmic reticulum stress, which leads to the attenuation of apoptosis and fatty acid synthesis.

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

“…For example, Kwon et al recently showed that betaine supplementation in mice inhibited hepatic fat accumulation and prevented the decrease in antioxidant capacity against free radicals induced by a high fat diet [39]. Choline metabolism intermediates SAM and betaine have also been shown to reduce pro-inflammatory cytokines such as tumour necrosis factor-a (TNF-a) and to inhibit apoptosis of hepatocytes in animals [40,41]. One hypothesis regarding this property of betaine is that it contains an electrophilic methyl group that may prevent and/or reduce reductive and oxidative stress [40].…”

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

“…SAM effect was largely studied in liver disease, also with attention to its antioxidant properties [9,[91][92]. SAM led to inhibition of liver lipid peroxidation in a rat model of acute biliary obstruction and reduced mitochondrial oxidative stress in a rat model of liver ischemia/reperfusion [93].…”

Effect of folic acid intervention on ALT concentration in hypertensives without known hepatic disease: a randomized, double-blind, controlled trial

“…Increasing evidence suggests that altered methionine/folate metabolism may contribute to the development of hepatic injury. Folate deficiency may accelerate or promote hepatic injury by increasing hepatic homocysteine and S-adenosylhomocysteine concentrations decreasing hepatic S-adenosylmethionine and glutathione concentrations increasing lipid peroxidation and decreasing global DNA methylation (Purohit et al, 2007). Hyperhomocysteine also may promote insulin resistance (Björck et al, 2006;Li et al, 2008) and alter lipid metabolism (Liao et al, 2006).…”