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SAM-e supplement: what it is and what the evidence shows

By the Life in Good Form editors. Updated 2026-10-15.

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What SAM-e is

The National Center for Complementary and Integrative Health (NCCIH) explains that SAM-e was discovered in the early 1950s and is made in the body from methionine, an amino acid in foods. It helps regulate key functions in cells. In Europe it is called ademetionine.

Abnormal SAM-e levels have been reported in liver disease and depression, which led researchers to test it for those conditions. The joint pain idea came from depression studies, where some participants with osteoarthritis said their joints felt better.

What the research shows

Depression. At least 40 human studies have tested SAM-e for depression, and many showed benefits. But most lasted only a few weeks, were small and were not of the highest quality, and some used injected SAM-e rather than pills. Overall, the evidence for oral SAM-e is not conclusive.

Osteoarthritis. Studies comparing oral SAM-e with NSAIDs, the common pain relievers for arthritis, found similar pain relief and joint function, with fewer side effects on SAM-e. The smaller number of placebo-controlled studies did not consistently show a benefit.

Liver. Low SAM-e levels are linked with liver disease, and animal studies are promising, but benefit in people has not been established. Research on alcoholic cirrhosis, hepatitis C, cholestasis, fatty liver disease and liver cancer prevention is inconclusive.

Other conditions studied

SAM-e has also been tested for fibromyalgia, migraine, schizophrenia, Alzheimer's disease and ADHD, but NCCIH says there is not enough evidence to reach conclusions for any of them.

Several studies tested SAM-e for intrahepatic cholestasis of pregnancy, a condition in the third trimester where bile flow from the liver slows and causes itching. Results conflicted, and data are insufficient to show whether it helps. Because SAM-e's safety in pregnancy is not established, any use in pregnancy belongs with an obstetrician.

A trial of SAM-e as a quit-smoking aid found it did not raise quit rates or reduce withdrawal symptoms.

Safety and interactions

• Bipolar disorder. SAM-e may worsen mania. People with bipolar disorder should not take it for depression except under medical supervision. NOW Foods' label adds anxiety disorders to this warning.
• Antidepressants and serotonin. SAM-e might interact with antidepressants, L-tryptophan and St. John's wort, which also raise serotonin.
• Parkinson's disease. SAM-e may reduce the effect of levodopa.
• Weakened immunity. There is a theoretical concern for people who are immunocompromised, such as those who are HIV-positive, because SAM-e enhances growth of the Pneumocystis organism.
• Pregnancy. Safety in pregnancy has not been established.
• Side effects. Uncommon and usually minor, such as nausea or digestive upset. In one 2-year liver study, no serious side effects were reported.

Doses and forms

• Tablets. NOW Foods' SAMe 400 mg directs 1 tablet 2 to 4 times daily, preferably on an empty stomach; NOW Foods also sells 200 mg strengths.
• Coating. Enteric coated tablets and caplets are among the forms sold.
• Forms of SAM-e. NOW Foods lists SAM-e from S-adenosyl-L-methionine disulfate tosylate. Check the form and amount of actual SAM-e per tablet.
• Higher doses should be discussed with a doctor, especially for depression.

How to choose a SAM-e supplement

• Get a diagnosis first. NCCIH warns not to use SAM-e to postpone seeing a provider. Depression needs professional care.
• Check the mg per tablet and directions; doses add up quickly at 2 to 4 tablets a day.
• Check medicines for serotonin-raising drugs and levodopa.
• Store as directed. NOW Foods says to store it in a cool, dry place after opening.
• Children. Consult your child's provider before giving SAM-e to a child.

What to look for when you buy

Questions people ask

What is SAM-e supplement used for?

Mainly depression, osteoarthritis and liver health. NCCIH says evidence is promising but not conclusive for all three.

Does SAM-e help joint pain?

Studies found it worked about as well as NSAIDs with fewer side effects, but placebo-controlled studies were inconsistent.

Can I take SAM-e with antidepressants?

Only under medical supervision. SAM-e may interact with drugs that raise serotonin.

What are SAM-e side effects?

Usually minor nausea or digestive upset. It may worsen mania in bipolar disorder.

How should I take SAM-e?

Follow the label. NOW Foods directs 1 tablet 2 to 4 times daily, preferably on an empty stomach.

Sources

• S-Adenosyl-L-Methionine (SAMe): In Depth (nccih.nih.gov), National Center for Complementary and Integrative Health
• SAMe 400 mg Tablets (www.nowfoods.com/products/supplements/same-400-mg-tablets), NOW Foods

Sources checked 2026-10-15.