S-Adenosyl-Methionine · supplement
Evidence tier: weak
A foundational methylation cofactor with strong evidence for mood, joint, and liver support.
SAMe is the body's universal methyl donor. It hands off a methyl group in hundreds of reactions, including the synthesis and breakdown of the monoamine neurotransmitters and the maintenance of cell membranes and glutathione in the liver. The biochemistry is textbook and not in dispute. What is in dispute is whether swallowing more of it changes anything, and that is a different question from whether the molecule matters. SAMe is also chemically unstable, poorly absorbed and expensive, so what reaches the tissue from a capsule is not the same as what the biochemistry describes.
Weak, and pointed at a target a supplement is not allowed to aim for. The Cochrane review of SAMe for depression in adults pooled 8 trials in 934 people and rated the certainty of evidence LOW to VERY LOW across every comparison. Against placebo as a standalone treatment there was no meaningful difference (very low quality). Against imipramine and against escitalopram it looked similar, which is an equivalence claim resting on low quality trials too small to detect a real gap, not a demonstration that it works. Only as an add on to an SSRI did it beat placebo, again on low quality evidence. Cochrane's own conclusion is that given the absence of high quality evidence and the inability to draw firm conclusions based on that evidence, the use of SAMe for the treatment of depression in adults should be investigated further (Galizia 2016, CD011286). NCCIH agrees: overall, the evidence that oral SAMe may be helpful for depression is not conclusive, and the trials were brief, small, and of limited quality. For osteoarthritis the Cochrane review (Rutjes 2009, CD007321) was inconclusive and hampered by small trials of questionable quality, and stated that routine use of SAMe should not be advised; NCCIH notes the trials that compared SAMe with placebo, as opposed to with NSAIDs, did not consistently show benefit. For liver disease NCCIH is blunt: whether SAMe is beneficial for liver diseases in people has not been established. Safety is where SAMe stops being a routine supplement. It is contraindicated in bipolar disorder because it can precipitate manic episodes, and NCCIH warns that people with bipolar disorder should not take SAMe for their depressive symptoms except under the supervision of a health care provider. Taken with antidepressants, St John's wort or L tryptophan it can raise serotonin and risks serotonin syndrome. It may also blunt levodopa in Parkinson's disease.
Trials and supplement practice run roughly 400 to 1600 mg daily, often split, and taken as an enteric coated tablet on an empty stomach. Low dose monotherapy appears least likely to do anything; the positive signals sit at higher doses and as an add on. No authority has established an effective dose because no authority has established an effect.
400 to 1600 mg daily, divided morning and midday, on an empty stomach. Enteric coated for stability.
CRITICAL interaction with SSRIs, MAOIs, and Parkinson's medications. Can trigger mania in bipolar disorder.
Pregnancy: avoid
Breastfeeding: avoid
Active compounds: S adenosyl L methionine
Remedies using SAM-e · Browse by body system · Check it against what you take
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.