S-Adenosyl-L-Methionine

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

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 References 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... read more ). 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 References 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... read more ). 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 References 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... read more ). In a small study, SAMe appeared to improve symptoms of depression that did not abate with treatment using a selective serotonin reuptake inhibitor (SSRI, 10 References 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... read more ). However, another study of SAMe plus an antidepressant compared to placebo plus an antidepressant showed an improvement in response and remission rates that was not statistically significant (3 References 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... read more ).

The clinical studies evaluating the health benefits of SAMe either are very small, lacking in proper methodology, or yield conflicting results among different trials.

A 2002 meta-analysis of osteoarthritis patients (6 References 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... read more ) 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, or osteoarthritis.

No serious adverse effects have been reported with dosages between 200 and 1200 mg a day.

Adverse effects of SAMe are uncommon, and when they do occur, they are usually minor problems such as nausea, gas, diarrhea, constipation, dry mouth, or headache.

SAMe is contraindicated in patients with bipolar disorder because SAMe can precipitate manic episodes.

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 serotonin syndrome Serotonin Syndrome Serotonin syndrome is a potentially life-threatening condition resulting from increased central nervous system serotonergic activity that is usually drug related. Symptoms may include mental... read more .

SAMe may also methylate levodopa, thus decreasing levodopa levels and diminishing the effectiveness of drugs that aim to treat Parkinson disease by increasing levodopa levels.

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