SAMe

S-Adenosylmethionine · S-Adenosyl-L-Methionine · Ademetionine

Snapshot

Indications	Contraindications
Depressive symptoms¹ Mild-to-moderate depression² Primary biliary cholangitis³ Neuropsychiatric comorbidity⁴	Bipolar disorder⁵ Methionine cycle defects⁶

S-adenosylmethionine (SAMe), also called ademetionine, is the body's principal methyl donor, supporting methylation reactions in brain and liver. Supplementation is used for depressive symptoms, where a meta-analysis found monotherapy superior to placebo¹, and for primary biliary cholangitis alongside ursodeoxycholic acid³. Typical users are adults with mild-to-moderate depressive symptoms.

Added to antidepressants, SAMe did not differ from placebo, and against antidepressants alone it showed no significant difference¹. In a 2022 laboratory study of biological rhythms, excess SAMe was catabolized to adenine and methylthioadenosine, which inhibit methylation; no human trial has tested this. Products listing SAMe are mostly tablets or capsules; see Form comparison.

Antidepressant cautions are about coordination: per product labels, SAMe is not to be combined with antidepressants unless under close supervision of a health care professional⁵. The Italian label reports serotonin syndrome with clomipramine and advises caution with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants⁶.

Last updated October 15, 2026. Read how we make monographs.

In the full monograph

30 sources, 22 studies

When to useThe situations practitioners use it for, each with the reason and the study behind it.
SafetyWho should avoid it, who needs extra care, and the side effects reported in studies.
InteractionsThe medicines and supplements it interacts with, the effect of each, and what labeling says to watch.
Protocol notesThe doses used in studies, how and when they were taken, and how the forms on the market compare.
How it worksWhat it is and how it works in the body, in plain terms.
Published studiesThe studies behind each use, popular claims checked against them, and trials still under way.
Word of mouthWhat patients and practitioners report online, kept separate from the clinical evidence.
Clinical perspectiveA closing read of where the evidence is solid, where it is thin, and what has not been studied.

Snapshot

In the full monograph

Sources