S-Adenosyl-l-methionine (SAMe) is a derivative of methionine and a cofactor for multiple synthetic pathways, particularly as a methyl group donor. It is produced naturally in the body, mainly by the liver, and is manufactured synthetically in supplement form.
(See also Overview of Dietary Supplements.)
Claims
Evidence
A 2016 Cochrane review of 8 trials (934 subjects) found lack of high-quality evidence to support SAMe use in depression treatment and recommended further evaluation in high-quality randomized controlled trials (1). An 8-week randomized control trial of SAMe for depression (a pilot study of 49 patients) reported that SAMe use resulted in a reduction of depression symptoms per the Montgomery-Asberg Depression Rating Scale (MADRS) that was clinically but not statistically significant (2). Per exploratory analysis in this trial, SAMe reduced symptoms of milder depression. In a different study, when SAMe was used adjunctively with antidepressants, although depression scores decreased over time, there were no differences between SAMe treated and untreated groups (3). The clinical studies evaluating the health benefits of SAMe either are very small, lacking in proper methodology, or yield conflicting results among different trials. However, a 2002 meta-analysis of osteoarthritis patients (6) indicated that SAMe was more effective than placebo in reducing functional limitations associated with osteoarthritis. More importantly, in 2 studies evaluated in this analysis, SAMe (1200 mg/day, eg, at 600 mg orally twice a day) was as efficacious as nonsteroidal anti-inflammatory drugs (NSAIDs), but without the adverse effects common with NSAID use.
More high-quality studies are needed with standardized supplements before recommendations can be made for the supplementation of SAMe for the treatment of depression, liver disorders, and osteoarthritis.
Adverse effects
Drug interactions
S -Adenosyl- l -methionine references
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Galizia I, Oldani L, Macritchie K, et al: S-adenosyl methionine (SAMe) for depression in adults (review). Cochrane Database Syst Rev 10:CD011286, 2016. doi: 10.1002/14651858.CD011286.pub2.
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Sarris J, Murphy J, Stough C, et al: S-adenosylmethionine (SAMe) monotherapy for depression: an 8-week double-blind, randomised, controlled trial. Psychopharmacology (Berl) 237(1):209-218, 2020. doi: 10.1007/s00213-019-05358-1.
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Sarris, Byrne GJ, Bousman C, et al: Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: an 8-week double-blind, randomized, controlled trial. Eur Neuropsychopharmacol. 28(10):1126-1136, 2018. doi: 10.1016/j.euroneuro.2018.07.098.
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Rutjes AW, Nüesch E, Reichenbach S, et al: S-Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database Syst Rev (4) CD007321, 2009. doi: 10.1002/14651858.CD007321.pub2.
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De Silva V, El-Metwally A, Ernst E, et al; Arthritis Research UK Working Group on Complementary and Alternative Medicines: Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford) 50(5):911-920, 2011. doi: 10.1093/rheumatology/keq379.
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Soeken KL, Lee WL, Bausell RB, et al: Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract 51(5):425-430, 2002.
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Gurung V, Middleton P, Milan SJ, et al: Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev 6:CD000493, 2013. doi: 10.1002/14651858.CD000493.pub2.
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Rambaldi A, Gluud C: S-adenosyl-L-methionine for alcoholic liver diseases. Cochrane Database Syst Rev (2):CD002235, 2006. doi: 10.1002/14651858.CD002235.pub2.
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De la Cruz JP, Mérida M, González-Correa JA, et al: Effects of S-adenosyl-L-methionine on blood platelet activation. Gen Pharmacol 29(4):651-655, 1997.
More Information
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
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National Institutes of Health (NIH), National Center for Complementary and Integrative Health: Information on research regarding the use of SAMe for depression, osteoarthritis, and liver diseases
