SAMe
S-adenosylmethionine
Supplements. Modern nutrition.
Also called Ademetionine, S-adenosyl-L-methionine
Pinyin: xiàn gān dàn ān suān
Spanish: S-adenosilmetionina
Avoid with bipolar disorderA compound your cells make from methionine, an amino acid, and sold as a supplement mostly for mood and joint pain.
Did you know? Every cell makes SAMe, which acts as the main 'methyl donor' for many reactions, including the ones that help switch genes on and off.
What it may help, and how strong the proof is
- Low mood. Some trials report a small mood lift over placebo. A 2016 Cochrane review of 8 trials (about 930 adults) found no significant benefit over placebo in its placebo comparison, could not draw firm conclusions because the trials were low in quality, and called for larger, better trials.See the research: 6,522 studies in peoplePromising proof
- Joint pain & arthritis. Trials in knee or hip osteoarthritis give mixed results. A Cochrane review found only a small pain benefit over placebo, with no clear effect on function, and it advised against routine use.See the research: 1,896 studies in peoplePromising proof
- Liver. Used in Europe for liver problems. In a 2-year trial of 123 people with alcohol-related cirrhosis, SAMe did not show a clear survival benefit on its main measure. A subgroup analysis that left out the sickest patients looked better.See the research: 3,059 studies in peopleUnproven
Parts of the body
Traditional use
SAMe is not part of old herbal healing. It was first found in the 1950s. Some European countries later sold it as a prescription medicine, and in the US it is a dietary supplement.
How it is classified
How people take it
Depression and arthritis trials mostly used 400 to 1,600 mg a day, often split into doses, for weeks. SAMe breaks down easily with heat, moisture and air, so store it cool and dry. Talk with a doctor first, especially if you take antidepressants or have bipolar disorder.
Capsule and tablet.
Where to get it
Your body makes SAMe from methionine, which is found in eggs, fish, meat, sesame seeds and Brazil nuts. Supplements are made in labs and sold as enteric-coated tablets, which are coated to survive stomach acid. Quality varies between brands.
Be careful
Common side effects are upset stomach, diarrhea, dry mouth, sweating, headache and trouble sleeping. It can trigger mania in people with bipolar disorder, so it is generally avoided there. Combining it with antidepressants may raise the risk of serotonin syndrome, a rare but serious reaction. Safety in pregnancy and breastfeeding is not well studied.
Avoid if: pregnancy; breastfeeding; bipolar disorder.
Mixing with other things
- Works well together
Folate and vitamin B12 help the body recycle methionine, the building block of SAMe.
- Works well together
B12 works alongside folate in the same recycling step, so the two are often sold together.
- Don't mixAntidepressants (Zoloft, Prozac, Lexapro and others)
Do not mix with SSRI, SNRI or MAOI antidepressants unless a doctor oversees it. The combination may cause serotonin syndrome.
The honest take
SAMe is a real body chemical, and some trials suggest mood and joint benefits. The proof is still small and mixed, and the best reviews call for stronger trials. Liver claims are not yet backed by a clear survival benefit in trials. It can trigger mania and interacts with antidepressants, so use it only with medical advice.
Sources
Each “See the research” link opens PubMed, the U.S. National Library of Medicine's index of medical studies, showing only trials and reviews done in people. The number tells you how much a use has been tested, not whether it worked. The proof rating tells you that.
Study counts checked October 2026.