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S -Adenosyl- l -Methionine


By Melissa G. Marko, PhD, Senior Clinical Scientist, Nestle Nutrition
Ara DerMarderosian, PhD, Professor Emeritus of Biology and Pharmacognosy, University of the Sciences

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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, 2), osteoarthritis (3-5), cholestasis (6), and liver disorders (7). In addition, mechanistically SAMe has been shown to be a platelet inhibitor (8).


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 (5) 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 po bid) 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