S-adenosylmethionine is made in the body from ATP and methionine and is produced, broken down, and regenerated in a series of steps known as the SAM (S-adenosylmethionine) cycle.^[1][2][3] S-adenosylmethionine circulates in the blood and cerebrospinal fluid, and its major role is as a “methyl donor”, where it provides a methyl group (CH₃; three hydrogen atoms attached to a carbon atom) for important biological reactions in the body.^[1][2][3] However, it can also donate adenosyl groups, amino groups (NH₃), and more in other enzymatic reactions.^[4]

S-adenosylmethionine regulates several important biological processes including DNA methylation, immune responses, and amino acid metabolism^[1][2][3] and is sold as a food supplement claimed to improve several conditions. In some countries, S-adenosylmethionine is also available as a prescription drug.

Low levels of S-adenosylmethionine have been found in people with liver conditions (nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cirrhosis, etc.),^[1][5][6] chronic kidney disease (CKD),^[7] coronary artery disease (CAD),^[8][9] depression,^[10][11][12] and some neurodegenerative conditions like dementia and Alzheimer’s disease.^[12][13] These observations suggest that supplementation could help treat such conditions. However, while S-adenosylmethionine has shown therapeutic effects in cell-culture experiments and animal models,^[1][5][14] its therapeutic benefit in humans is less convincing.

Current evidence shows that S-adenosylmethionine might help treat depression^{[15][16][17][18]} and might improve liver health and survival in people with liver conditions like cirrhosis.^[19][20][21] However, due to the low quality of evidence, further large, double-blind randomized controlled trials are needed to clarify the clinical efficacy of S-adenosylmethionine.

Despite the popularity of S-adenosylmethionine as a dietary supplement, the main drawback is the lack of high-quality evidence supporting its claimed clinical efficacy (as discussed above). Furthermore, some case studies of patients with underlying conditions have reported serious adverse effects, including manic episodes with suicidal thoughts.^{[22][23][24][25]} For this reason, people with bipolar disorder should consult their doctor before considering using S-adenosylmethionine.

Other studies have reported side effects including headaches, insomnia, and nausea,^[26][15][27] while further studies have highlighted safety concerns when S-adenosylmethionine is consumed in excess.^[28] However, adverse effects are rare and side effects are uncommon, so S-adenosylmethionine is generally considered safe to consume.^{[24][26][15][27]} That said, Cochrane reviews on S-adenosylmethionine note that studies in this field rarely document adverse events.^[15][27]

S-adenosylmethionine regulates biological processes by transferring methyl groups, adenosyl groups, amino groups, and more to proteins, lipids, nucleic acids (e.g., DNA), and several other metabolites in many enzymatic reactions.^[1][4][2][3]

Because several conditions — liver disease, kidney disease, heart disease, and neurodegenerative conditions, etc. — are associated with low levels of S-adenosylmethionine in blood or tissues,^{[1][5][6][7][8][9][12][13]} supplementation might help restore normal levels. However, even if this is possible, the evidence supporting the therapeutic efficacy of supplementation with S-adenosylmethionine is weak (as described above).