# SAM-e (S-adenosylmethionine)

Source: https://onco.cc/technologies/sam-e-supplements/  
OnCo record `sam-e-supplements` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

SAM-e is sold for mood, joints and the liver. Evidence for depression is mixed, it did not help hot flushes, and small studies of protecting the liver during chemotherapy need confirming. It can trigger mania in bipolar disorder and adds to the serotonin effects of antidepressants.

## Summary

S-adenosylmethionine is the body's main methyl donor and is involved in making serotonin and noradrenaline; it is a supplement in the United States and a prescription drug in some other countries. Memorial Sloan Kettering's About Herbs entry finds mixed data for depression, whether as an add-on or compared with escitalopram, with several double-blind studies negative; results for osteoarthritis are mixed, and an expert panel found insufficient evidence for pain. For hot flushes SAM-e was ineffective compared with historical placebo. In liver disease some trials suggest benefit, but in hepatitis C cirrhosis at high risk of liver cancer it did not improve liver function or injury markers. Preliminary data suggest it may help as palliative adjunct therapy in advanced biliary tract cancer or protect against chemotherapy liver toxicity; these need confirming. It is generally well tolerated but has caused mania in people with bipolar disorder and serotonin syndrome with clomipramine; MSK advises avoiding it with antidepressants, 5-HTP or St John's wort, notes it may reduce the effect of levodopa, and flags a theoretical concern about Pneumocystis infection in immunocompromised people.

## Fields

- Kind: Technology
- Status: phase-2
- Last checked: 2026-11-04
- Also known as: SAMe; S-adenosyl-L-methionine; Ademetionine
- Tags: complementary; supportive-care; evidence:insufficient
- Principle: Donates methyl groups for neurotransmitter, phospholipid and glutathione synthesis; poorly absorbed, so enteric-coated tablets are used.
- Strengths: Generally well tolerated; Preliminary signals in chemotherapy liver toxicity and biliary cancer palliation
- Limitations: Mixed depression evidence; ineffective for hot flushes; Mania in bipolar disorder; serotonin interactions; Theoretical infection concern when immunocompromised

## Sources

- MSK About Herbs: SAM-e (page last updated 9 November 2022): https://www.mskcc.org/cancer-care/integrative-medicine/herbs/sam-e

## Connected records

- technologies: [5-HTP (5-hydroxytryptophan)](https://onco.cc/technologies/five-htp-supplements/), [Dietary supplements during cancer treatment: interactions and harms](https://onco.cc/technologies/dietary-supplements-treatment-interactions/), [Evidence-based integrative oncology](https://onco.cc/technologies/integrative-oncology/), [N-acetylcysteine (NAC) supplements](https://onco.cc/technologies/n-acetylcysteine-supplements/), [Psycho-oncology and distress screening](https://onco.cc/technologies/psycho-oncology/)
- fronts: [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)

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