S-Adenosyl Methionine
S-adenosyl-L-methionine, usually shortened to SAMe, is a compound the body makes from the amino acid methionine. It is also manufactured as a supplement.
Also listed as SAME, SAMe, Ademethionine, S-adenosyl-L-methionine
A meaningful signal in depression research
A 2024 meta-analysis included 23 randomized trials with 2,183 participants. When used on its own, SAMe reduced depressive symptoms more than placebo; the authors judged this evidence moderately certain. However, adding SAMe to antidepressants did not produce a statistically clear benefit over adding placebo. The difference matters: evidence for one treatment approach does not establish the other. 1
How does it compare with antidepressants?
The same review found no statistically significant difference between SAMe and antidepressants, but uncertainty about their comparative efficacy remained. That result does not establish that the treatments are interchangeable. NCCIH notes that many studies have been small or short, and some tested injected rather than oral SAMe. 1 2
What about osteoarthritis?
Studies have explored whether SAMe helps joint pain and function. Comparisons with anti-inflammatory medicines have sometimes looked favorable, but placebo-controlled findings are less consistent. The German-language MSD Manual highlights older findings for function rather than pain, a useful reminder that these outcomes are not identical. 2 3
Liver blood tests are only part of the story
A 2024 systematic review collected studies across different liver conditions, routes of administration and combination treatments. Some reported improved blood tests or symptoms. Yet a placebo-controlled trial in alcohol-related liver disease, using 1,200 mg daily for 24 weeks, found no between-group differences in the reported liver blood tests. These mixed results do not establish that SAMe prevents liver failure or improves survival. 4
Does this translate into everyday mental energy?
The depression trials examined depressive symptoms, not a general promise of sharper focus or more mental energy in healthy people. NCCIH also describes the evidence for conditions such as ADHD, Alzheimer’s disease and fibromyalgia as too limited for conclusions. These remain research questions rather than established reasons for routine supplementation. 1 2
Effects by health goal
Open an effect to see the studies behind its rating. Bars show the size of the effect; the letter grades the evidence.
Stress & Mood2 effects
No study is linked to this rating.
Essential Health1 effect
Longevity1 effect
No study is linked to this rating.
Organ Function2 effects
Bone & Joint1 effect
Cognition4 effects
No study is linked to this rating.
No study is linked to this rating.
Other effects1 effect
No study is linked to this rating.
All studies
10 publications are linked to S-Adenosyl Methionine, newest first.
Sources
- Efficacy and acceptability of S-adenosyl-L-methionine for depressed patients: A systematic review and meta-analysis Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2024 · Study record
- S-Adenosyl-L-Methionin (SAM) MSD Manual, 2026