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. Healthy methylation is vital for cellular health, hormone and neurotransmitter production, and energy metabolism. SAMe also functions as a precursor molecule for glutathione and promotes polyamine synthesis to promote healthy cellular function. The polyamines spermidine and spermine maintain healthy cell growth and cytokine balance. Clinical trials indicate that SAMe administration enhances glutathione production in hepatic tissue and red blood cells. SAMe also supports cognitive function and mood. In a meta-analysis involving 25 controlled trials and 791 individuals, SAMe offered statistically significant support for positive mood. While the exact mechanism for this benefit has not been determined, it is believed that SAMe supports neurotransmitter monoamine synthesis and function, including dopamine and serotonin, through SAMe-dependent methylation reactions. By supporting methylation, SAMe promotesphosphatidylcholine production and cellular membrane integrity and fluidity. Multiple clinical trials indicate that SAMe supports joint comfort and flexibility. In a meta-analysis involving 11 studies, SAMe offered statistically significant support for joint function. In another 16-week, randomized, double-blind, placebo-controlled trial involving 56 subjects, SAMe offered statistically significant support for joint comfort. It is believed that SAMe enhances joint comfort and function by supporting proteoglycan synthesis, and by helping to stabilize and protect the proteoglycans.