What is S-adenosylmethionine?
S-adenosylmethionine is made in the body from ATP and methionine and is produced, broken down, and regenerated in a series of steps known as the SAM (S-adenosylmethionine) cycle.[1][2][3] S-adenosylmethionine circulates in the blood and cerebrospinal fluid, and its major role is as a “methyl donor”, where it provides a methyl group (CH3; three hydrogen atoms attached to a carbon atom) for important biological reactions in the body.[1][2][3] However, it can also donate adenosyl groups, amino groups (NH3), and more in other enzymatic reactions.[4]
S-adenosylmethionine regulates several important biological processes including DNA methylation, immune responses, and amino acid metabolism[1][2][3] and is sold as a food supplement claimed to improve several conditions. In some countries, S-adenosylmethionine is also available as a prescription drug.
What are S-adenosylmethionine’s main benefits?
Low levels of S-adenosylmethionine have been found in people with liver conditions (nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cirrhosis, etc.),[1][5][6] chronic kidney disease (CKD),[7] coronary artery disease (CAD),[8][9] depression,[10][11][12] and some neurodegenerative conditions like dementia and Alzheimer’s disease.[12][13] These observations suggest that supplementation could help treat such conditions. However, while S-adenosylmethionine has shown therapeutic effects in cell-culture experiments and animal models,[1][5][14] its therapeutic benefit in humans is less convincing.
Current evidence shows that S-adenosylmethionine might help treat depression[15][16][17][18] and might improve liver health and survival in people with liver conditions like cirrhosis.[19][20][21] However, due to the low quality of evidence, further large, double-blind randomized controlled trials are needed to clarify the clinical efficacy of S-adenosylmethionine.
What are S-adenosylmethionine’s main drawbacks?
Despite the popularity of S-adenosylmethionine as a dietary supplement, the main drawback is the lack of high-quality evidence supporting its claimed clinical efficacy (as discussed above). Furthermore, some case studies of patients with underlying conditions have reported serious adverse effects, including manic episodes with suicidal thoughts.[22][23][24][25] For this reason, people with bipolar disorder should consult their doctor before considering using S-adenosylmethionine.
Other studies have reported side effects including headaches, insomnia, and nausea,[26][15][27] while further studies have highlighted safety concerns when S-adenosylmethionine is consumed in excess.[28] However, adverse effects are rare and side effects are uncommon, so S-adenosylmethionine is generally considered safe to consume.[24][26][15][27] That said, Cochrane reviews on S-adenosylmethionine note that studies in this field rarely document adverse events.[15][27]
How does S-adenosylmethionine work?
S-adenosylmethionine regulates biological processes by transferring methyl groups, adenosyl groups, amino groups, and more to proteins, lipids, nucleic acids (e.g., DNA), and several other metabolites in many enzymatic reactions.[1][4][2][3]
Because several conditions — liver disease, kidney disease, heart disease, and neurodegenerative conditions, etc. — are associated with low levels of S-adenosylmethionine in blood or tissues,[1][5][6][7][8][9][12][13] supplementation might help restore normal levels. However, even if this is possible, the evidence supporting the therapeutic efficacy of supplementation with S-adenosylmethionine is weak (as described above).
What are other names for S-adenosylmethionine
- SAM
- SAMe
- SAM-e
- Adomet
- Ademetionine
- S-adenosyl-L-methionine
- Methionine
Dosage information
Formulations: Tablets taken orally, or liquid injected intravenously or intramuscularly.
Range of dosages studied: 45 to 3200 milligrams per day (mg/day).
Dosage recommendation: In some studies, the dosage range that has been found to improve depression is approximately 200 to 1,600 mg/day. In some studies, the dosage range that has been found to improve liver health in people with chronic liver conditions is approximately 800 to 1,200 mg/day
Take with food: S-adenosylmethionine can be taken with or without food.
Safety information:
S-adenosylmethionine can interact with several drugs including drugs that affect serotonin, including Selective Serotonin Reuptake Inhibitors and Monoamine Oxidase Inhibitors. Due to the increased risk of mania, S-adenosylmethionine is not recommended for people with bipolar disorder.
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Frequently asked questions
S-adenosylmethionine is made in the body from ATP and methionine and is produced, broken down, and regenerated in a series of steps known as the SAM (S-adenosylmethionine) cycle.[1][2][3] S-adenosylmethionine circulates in the blood and cerebrospinal fluid, and its major role is as a “methyl donor”, where it provides a methyl group (CH3; three hydrogen atoms attached to a carbon atom) for important biological reactions in the body.[1][2][3] However, it can also donate adenosyl groups, amino groups (NH3), and more in other enzymatic reactions.[4]
S-adenosylmethionine regulates several important biological processes including DNA methylation, immune responses, and amino acid metabolism[1][2][3] and is sold as a food supplement claimed to improve several conditions. In some countries, S-adenosylmethionine is also available as a prescription drug.
The S-adenosylmethionine (SAM) cycle is a series of metabolic steps that produce, break down, and regenerate S-adenosylmethionine.[1][2][3] The SAM cycle converts S-adenosylmethionine to S-adenosylhomocysteine to homocysteine to methionine and back to S-adenosylmethionine using various enzymes.[1][2][3] The enzymatic conversion of homocysteine to methionine in the SAM cycle uses vitamin B12 as a cofactor and links the SAM cycle to the folate cycle to make up a complex series of metabolic pathways known as one-carbon metabolism.[29] It is called one-carbon metabolism because these processes produce and provide one-carbon methyl groups (CH3) for several important biological processes (DNA synthesis, DNA methylation, immune function, amino acid metabolism, etc.).[1][2][3][29]
Low levels of S-adenosylmethionine have been found in people with liver conditions (nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cirrhosis, etc.),[1][5][6] chronic kidney disease (CKD),[7] coronary artery disease (CAD),[8][9] depression,[10][11][12] and some neurodegenerative conditions like dementia and Alzheimer’s disease.[12][13] These observations suggest that supplementation could help treat such conditions. However, while S-adenosylmethionine has shown therapeutic effects in cell-culture experiments and animal models,[1][5][14] its therapeutic benefit in humans is less convincing.
Current evidence shows that S-adenosylmethionine might help treat depression[15][16][17][18] and might improve liver health and survival in people with liver conditions like cirrhosis.[19][20][21] However, due to the low quality of evidence, further large, double-blind randomized controlled trials are needed to clarify the clinical efficacy of S-adenosylmethionine.
S-adenosylmethionine is claimed to improve joint pain and function in people with knee or hip osteoarthritis. However, studies in this field are small, and their methodological quality is generally low. Consequently, higher-quality evidence is needed to make clear conclusions.[26][27]
Despite the popularity of S-adenosylmethionine as a dietary supplement, the main drawback is the lack of high-quality evidence supporting its claimed clinical efficacy (as discussed above). Furthermore, some case studies of patients with underlying conditions have reported serious adverse effects, including manic episodes with suicidal thoughts.[22][23][24][25] For this reason, people with bipolar disorder should consult their doctor before considering using S-adenosylmethionine.
Other studies have reported side effects including headaches, insomnia, and nausea,[26][15][27] while further studies have highlighted safety concerns when S-adenosylmethionine is consumed in excess.[28] However, adverse effects are rare and side effects are uncommon, so S-adenosylmethionine is generally considered safe to consume.[24][26][15][27] That said, Cochrane reviews on S-adenosylmethionine note that studies in this field rarely document adverse events.[15][27]
S-adenosylmethionine regulates biological processes by transferring methyl groups, adenosyl groups, amino groups, and more to proteins, lipids, nucleic acids (e.g., DNA), and several other metabolites in many enzymatic reactions.[1][4][2][3]
Because several conditions — liver disease, kidney disease, heart disease, and neurodegenerative conditions, etc. — are associated with low levels of S-adenosylmethionine in blood or tissues,[1][5][6][7][8][9][12][13] supplementation might help restore normal levels. However, even if this is possible, the evidence supporting the therapeutic efficacy of supplementation with S-adenosylmethionine is weak (as described above).
In humans, intravenous administration of S-adenosylmethionine (100 mg, 500 mg, and 0.5 mg/kg of body weight) directly into the bloodstream has a half-life of approximately 80 to 100 minutes.[30][31] Furthermore, there are detectable increases in S-adenosylmethionine concentrations in the blood and the cerebrospinal fluid after oral, intravenous, and intramuscular administration, suggesting that S-adenosylmethionine crosses the blood-brain barrier.[32]
In humans, intramuscular administration of S-adenosylmethionine (0.5 mg/kg of body weight) shows approximately 80–90% bioavailability — i.e., 80–90% of S-adenosylmethionine injected into a muscle appears in the blood.[30] However, when orally administered in humans, the bioavailability of S-adenosylmethionine is poorer,[32][24] as low as 2–3% in some studies.[33] However, some studies show that enteric-coated capsules of S-adenosylmethionine, which are protected from degradation by stomach acid, have improved bioavailability in humans when compared to uncoated S-adenosylmethionine.[34][35] Novel formulations such as phytate salts[36] and solid lipid nanoparticles[37] have further improved oral bioavailability in rodents, but these formulations remain to be tested in humans.
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References
Examine Database References
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- Homocysteine - Thompson MA, Bauer BA, Loehrer LL, Cha SS, Mandrekar JN, Sood A, Wahner-Roedler DLDietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trialJ Altern Complement Med.(2009 May)
- Homocysteine - Gören JL, Stoll AL, Damico KE, Sarmiento IA, Cohen BMBioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humansPharmacotherapy.(2004 Nov)
- Depression Symptoms - A Di Rocco, J D Rogers, R Brown, P Werner, T BottiglieriS-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trialMov Disord.(2000 Nov)
- Osteoarthritis Symptoms - Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BMSafety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritisJ Fam Pract.(2002 May)
- Osteoarthritis Symptoms - Kim J, Lee EY, Koh EM, Cha HS, Yoo B, Lee CK, Lee YJ, Ryu H, Lee KH, Song YWComparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patientsClin Ther.(2009 Dec)
- Osteoarthritis Symptoms - Caruso I, Pietrogrande VItalian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint diseaseAm J Med.(1987 Nov 20)
- Osteoarthritis Symptoms - Wadie I Najm, Sibylle Reinsch, Fred Hoehler, Jerome S Tobis, Phillip W HarveyS-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]BMC Musculoskelet Disord.(2004 Feb 26)
- Osteoarthritis Symptoms - Hardy ML, Coulter I, Morton SC, Favreau J, Venuturupalli S, Chiappelli F, Rossi F, Orshansky G, Jungvig LK, Roth EA, Suttorp MJ, Shekelle PS-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease.Evid Rep Technol Assess (Summ).(2003 Aug)
- Osteoarthritis Symptoms - Rutjes AW, Nüesch E, Reichenbach S, Jüni PS-Adenosylmethionine for osteoarthritis of the knee or hip.Cochrane Database Syst Rev.(2009 Oct 7)
- Fibromyalgia Symptoms - Jacobsen S, Danneskiold-Samsøe B, Andersen RBOral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluationScand J Rheumatol.(1991)
- Liver Fibrosis - Medici V, Virata MC, Peerson JM, Stabler SP, French SW, Gregory JF 3rd, Albanese A, Bowlus CL, Devaraj S, Panacek EA, Richards JR, Halsted CHS-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trialAlcohol Clin Exp Res.(2011 Nov)
- Cholestasis - Binder T, Salaj P, Zima T, Vítek LRandomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis of pregnancyJ Perinat Med.(2006)
- Cholestasis - Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JGPharmacological interventions for treating intrahepatic cholestasis of pregnancy.Cochrane Database Syst Rev.(2020 Jul 27)
- Depression Symptoms - Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava MS-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trialAm J Psychiatry.(2010 Aug)
- Depression Symptoms - Sarris J, Papakostas GI, Vitolo O, Fava M, Mischoulon DS-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of responseJ Affect Disord.(2014 Aug)
- Depression Symptoms - Ilaria Galizia, Lucio Oldani, Karine Macritchie, Erica Amari, Dominic Dougall, Tessa N Jones, Raymond W Lam, Guido Jacopo Massei, Lakshmi N Yatham, Allan H YoungS-adenosyl methionine (SAMe) for depression in adultsCochrane Database Syst Rev.(2016 Oct 10)
- Depression Symptoms - Peng TR, Cheng HY, Wu TWS-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis.Gen Hosp Psychiatry.(2024 Jan-Feb)
- Depression Symptoms - Limveeraprajak N, Nakhawatchana S, Visukamol A, Siripakkaphant C, Suttajit S, Srisurapanont MEfficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis.Prog Neuropsychopharmacol Biol Psychiatry.(2024 Jun 8)
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- Early Virologic Response - Jordan J Feld, Apurva A Modi, Ramy El-Diwany, Yaron Rotman, Emmanuel Thomas, Golo Ahlenstiel, Rachel Titerence, Christopher Koh, Vera Cherepanov, Theo Heller, Marc G Ghany, Yoon Park, Jay H Hoofnagle, T Jake LiangS-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonrespondersGastroenterology.(2011 Mar)
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- Bilirubin - Tao Guo, Lei Chang, Yusha Xiao, Quanyan LiuS-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysisPLoS One.(2015 Mar 16)