SAMe (S-adenosylmethionine) is a metabolite present in all living cells. It functions as a donor of methyl groups in over 100 different reactions and contributes to the synthesis, activation and/or metabolism of hormones, neurotransmitters, nucleic acids, phospholipids and proteins. Methyl groups act as a signal throughout the body, regulating genetic expression and cellular function. SAMe also functions as a precursor molecule for glutathione and promotes polyamine synthesis to promote healthy cellular function. Clinical trials indicate that SAMe administration enhances glutathione production in hepatic tissue and red blood cells. SAMe also targets cognitive function and positive mood, as indicated in over 40 clinical studies. In a meta-analysis involving 25 controlled trials and 791 individuals, SAMe offered statistically significant support for positive mood believed to be due to its support for neurotransmitter monoamine synthesis and function, including dopamine and serotonin. It also promotes healthy protein turnover and maintains healthy phospholipid methylation to support phosphatidylcholine production and cellular membrane integrity and fluidity. Studies suggest it may enhance joint comfort and flexibility as well. In a meta-analysis involving 11 studies, SAMe offered statistically significant support for joint function. It is believed to enhance joint comfort and function by supporting proteoglycan synthesis, as well as helping to stabilize and protect the proteoglycans.^‡