SAMe (S-adenosyl-L-methionine): what the research says

S-adenosyl-L-methionine, abbreviated SAMe, SAM-e or SAM, is produced in the body from methionine, an amino acid found in food. It takes part in many chemical reactions in cells. The NCCIH notes it is sold in the United States as a dietary supplement and that it is known in Europe as ademetionine. It was discovered in the early 1950s.

Interest in SAMe grew because abnormal levels have been reported in depression and in liver disease. The idea of using it for osteoarthritis came from depression trials in which some participants who also had osteoarthritis said their joint symptoms improved.

The NCCIH reports that at least forty studies in people have evaluated SAMe for depression and many showed signs of benefit. It also stresses that most of these trials lasted only a few weeks, included few participants and were not of the highest scientific standard, and that some used injected SAMe rather than tablets. Overall it concludes the evidence for oral SAMe is not conclusive.

Depression is a medical condition with well-established treatments. NHS care includes talking therapies, antidepressant medicines and self-help, assessed and reviewed by a GP or mental health team. NCCIH advice is not to use SAMe to postpone seeing a health care provider about a medical problem.

For osteoarthritis of the knee or hip, studies comparing oral SAMe with non-steroidal anti-inflammatory drugs generally found similar pain relief and joint function, with fewer side effects in people taking SAMe. The smaller number of studies against placebo did not consistently show a benefit, so results are mixed.

SAMe has also been examined in liver diseases, including alcohol-related cirrhosis, hepatitis C, non-alcoholic steatohepatitis and various forms of cholestasis. In intrahepatic cholestasis of pregnancy, which typically presents in the third trimester with itching, studies gave conflicting results and the NCCIH says current data cannot show whether it helps. Itching in pregnancy should be raised with a midwife promptly, because it needs medical assessment.

Long-term safety information is limited because most participants took SAMe only briefly, although one study in alcohol-related liver disease ran for two years with no serious side effects reported. Side effects are described as uncommon and usually minor, such as nausea or digestive upset.

The NCCIH lists specific cautions. SAMe may worsen manic symptoms in bipolar disorder. It may decrease the effects of levodopa used in Parkinson's disease. It might interact with antidepressants, L-tryptophan and St John's wort that increase serotonin. There is a theoretical concern for immunocompromised people, including those who are HIV-positive, because SAMe enhances growth of the organism that causes Pneumocystis infection. Safety in pregnancy has not been established.

• Bipolar disorder: avoid unless supervised by a clinician.

• Parkinson's disease: discuss levodopa effects first.

• Antidepressants and other serotonin-raising products: ask a pharmacist.

• HIV or other immune suppression: take advice first.

• Pregnancy and breastfeeding: not established as safe; check first.

The NCCIH page is from the United States, where SAMe is a supplement. The FSA guidance for the UK says food supplements should not be sold with claims to prevent, treat or cure a medical condition, that anyone with a medical condition or taking prescribed medicines should check with a GP first, and that high-dose supplements should not be taken unless advised by a GP or healthcare specialist. I did not find a UK regulator page stating the classification of each SAMe product on sale, so labels and a pharmacist are the practical check.