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S -Adenosyl- l -Methionine



Laura Shane-McWhorter

, PharmD, University of Utah College of Pharmacy

Last full review/revision Jul 2020| Content last modified Jul 2020
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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.


SAMe is said to be effective for treatment of depression (1-3) osteoarthritis (4-6), cholestasis (7), and liver disorders (8). In addition, mechanistically SAMe has been shown to be a platelet inhibitor (9).


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

No serious adverse effects have been reported with dosages between 200 and 1200 mg/day. SAMe is contraindicated in patients with bipolar disorder because SAMe can precipitate manic episodes.

Drug interactions

Some care should be taken with antidepressant drugs taken in combination with SAMe, as both will increase serotonin levels, potentially resulting in adverse effects such as rapid heart rate and anxiety.

S -Adenosyl- l -methionine references

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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