S-Adenosylmethionine (SAMe)

S-Adenosylmethionine (SAMe)

Supplement Forms/Alternate Names

Ademetionine, S-adenosyl methionine, SAM


S-adenosylmethionine (SAMe) is a compound made from two substances found in the body. The body uses it to make energy. SAMe has been used to ease pain in the joints and improve symptoms of depression. SAMe can be taken as a pill or powder. It can also be injected into the muscle or bloodstream by a healthcare provider.


400 milligrams 3 to 4 times daily

What Research Shows

Likely Effective

May Be Effective

Not Enough Data to Assess

Editorial process and description of evidence categories can be found at EBSCO NAT Editorial Process.

Safety Notes

It is likely safe to take S-adenosylmethionine in small doses for a short time. Not enough studies have been done to say whether it is safe to take for a long period. It is also not known whether it is safe to take by women who are pregnant or breastfeeding.


Talk to your doctor about any supplements or therapy you would like to use. Some can interfere with treatment or make conditions worse, such as:

  • People taking antidepressants should talk to their doctors before taking S-adenosylmethionine. It may interact with the medicine.


A. Cholestasis in Pregnancy

A1. Gurung V, Middleton P, et al. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2013 Jun 24;(6):CD000493.

B. Chronic Liver Disease

B1. Guo T, Chang L, et al. S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis. PLoS One. 2015 Mar 16;10(3):e0122124.

C. Depression

C1. Williams AL, Girard C, et al. S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clin Invest Med. 2005;28(3):132-139.

C2. Freeman MP, Mischoulon D, et al. Complementary and alternative medicine for major depressive disorder: a meta-analysis of patient characteristics, placebo-response rates, and treatment outcomes relative to standard antidepressants. J Clin Psychiatry. 2010 Jun;71(6):682-688.

C3. Turner P, Kantaria R, et al. A systematic review and meta-analysis of the evidence base for add-on treatment for patients with major depressive disorder who have not responded to antidepressant treatment: a European perspective. J Psychopharmacol. 2014 Feb;28(2):85-98.

C4. Galizia I, Oldani L, et al. S-adenosyl methionine (SAMe) for depression in adults. Cochrane Database Syst Rev. 2016;10:CD011286.

C5. Sarris J, Murphy J, et al. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. 2016 Jun 1;173(6):575-587.

C6. Schefft C, Kilarski LL, et al. Efficacy of adding nutritional supplements in unipolar depression: A systematic review and meta-analysis. Eur Neuropsychopharmacol. 2017 Nov;27(11):1090-1109.

D. Fibromyalgia

D1. De Silva V, El-Metwally A, et al. Evidence for the efficacy of complementary and alternative medicines in the management of fibromyalgia: a systematic review. Rheumatology (Oxford). 2010 Jun;49(6):1063-1068.

E. Mood and Anxiety Disorders

E1. Ravindran AV, da Silva TL. Complementary and alternative therapies as add-on to pharmacotherapy for mood and anxiety disorders: a systematic review. J Affect Disord. 2013 Sep 25;150(3):707-719.

F. Neuropsychiatric Disorders

F1. Sharma A, Gerbarg P, et al. S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. J Clin Psychiatry. 2017 Jun;78(6):e656-e667.

G. Osteoarthritis

G1. Soeken KL, Lee WL, et al. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract. 2002 May;51(5):425-430.

G2. Rutjes AW, Nüesch E, et al. S-Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2009;(4):CD007321.

G3. De Silva V, El-Metwally A, et al. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford). 2011 May;50(5):911-920.

H. Smoking Cessation

H1. Hughes JR, Stead LF, et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014 Jan 8;(1):CD000031.

Last reviewed July 2019 by EBSCO NAT Review Board Eric Hurwitz, DC

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