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.