S-Adenosyl Methionine

Last Updated: September 28 2022

S-Adenosylmethionine (SAMe) is a methyl donating compound that circulates in the blood and provides methyl groups to maintain other metabolic reactions. Lowered SAMe levels are associated with depressive symptoms, and supplementation may aid a partial deficiency.

dosageDosage
examine-databaseExamine Database
research-feedResearch feed

S-Adenosyl Methionine is most often used for

Summary

S-Adenosyl Methionine (SAMe) is the amino acid methionine bound to an ATP molecule; this molecule circulates in the blood naturally and acts as a 'methyl donor'. A methyl group in chemistry is simply a carbon molecule (bound to some hydrogens), and donating a methyl group to other molecules can accelerate or preserve reactions in the body as a form of metabolic 'maintenance'. Choline is another prominent methyl donor in the body, but due to selectivity of some reactions the two are not necessarily interchangeable.

Some body states appear to be associated with lower circulating levels of SAMe, including osteoarthritis and depression where SAMe appears to hold potent therapeutic potential; after a build-up period of 1-2 months, supplemental SAMe at 800-1600mg daily appears to be as potent as some pharmaceutical options for both osteoarthritis and depression and appears to enhance some anti-depressants. Although lower circulating levels of SAMe are also seen in diabetes, the benefits of SAMe and glucose control are not as well established as depression and osteoarthritis.

SAMe appears to follow many nutrient-like motifs in the body, being regulated within a certain serum range and being associated with adverse effects when that range is perturbed. It potentially holds a lot of benefit in body states where circulating SAMe levels decline.

Although side-effects are not commonly reported with SAMe, numerous studies note a small set of participants who experience mania after supplementing SAMe. It is not common, but it does appear to be related to SAMe supplementation for unknown reasons; it has been reported in some persons without history of mania as well and does not appear to be related to any pathological condition per se.

What else is S-Adenosyl Methionine known as?
Note that S-Adenosyl Methionine is also known as:
  • SAME
  • SAMe
  • Ademethionine
  • S-adenosyl-L-methionine
  • Adomet
S-Adenosyl Methionine should not be confused with:
  • Methionine (the isolated amino acid)
Dosage information

Supplementation of S-adenosylmethionine tends to be in the 600-1,200mg range over the course of a day, divided into two or three separated doses with meals. The higher dosage (1,200mg) tends to be used more often, with the lower dosage (600mg) being used to cut costs.

For S-adenosylmethionine to benefit osteoarthritis, it appears to require a few weeks or up to a month of continual usage for benefits to show. Benefits to depressive symptoms may be much more rapid.

Join our supplement information course

Enter your email to get a FREE five-day course on supplements. 100% backed by science, we take an independent and unbiased approach to figure out what works (and what's a waste of time and money).

    The only 100% independent company. While everyone sells supplements, we only analyze research.

    Examine Database
    Evidence + Benefits at a glance

    Easily compare what works and what doesn't.

    Learn More

    Don't miss out on the latest research

    Enter your email and we'll keep you on top of the latest nutrition research, supplement myths, and more

      References
      2.^Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EHHomocysteine, folate, methylation, and monoamine metabolism in depressionJ Neurol Neurosurg Psychiatry.(2000 Aug)
      6.^Bell KM, Potkin SG, Carreon D, Plon LS-adenosylmethionine blood levels in major depression: changes with drug treatmentActa Neurol Scand Suppl.(1994)
      7.^Shippy RA, Mendez D, Jones K, Cergnul I, Karpiak SES-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDSBMC Psychiatry.(2004 Nov 11)
      9.^Bottiglieri T, Godfrey P, Flynn T, Carney MW, Toone BK, Reynolds EHCerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionineJ Neurol Neurosurg Psychiatry.(1990 Dec)
      10.^Poirier LA, Brown AT, Fink LM, Wise CK, Randolph CJ, Delongchamp RR, Fonseca VABlood S-adenosylmethionine concentrations and lymphocyte methylenetetrahydrofolate reductase activity in diabetes mellitus and diabetic nephropathyMetabolism.(2001 Sep)
      12.^Andreoli VM, Maffei F, Tonon GCS-adenosyl-L-methionine (SAMe) blood levels in schizophrenia and depressionMonogr Gesamtgeb Psychiatr Psychiatry Ser.(1978)
      13.^Strous RD, Ritsner MS, Adler S, Ratner Y, Maayan R, Kotler M, Lachman H, Weizman AImprovement of aggressive behavior and quality of life impairment following S-adenosyl-methionine (SAM-e) augmentation in schizophreniaEur Neuropsychopharmacol.(2009 Jan)
      14.^Stabler SP, Allen RH, Dolce ET, Johnson MAElevated serum S-adenosylhomocysteine in cobalamin-deficient elderly and response to treatmentAm J Clin Nutr.(2006 Dec)
      15.^Poirier LA, Wise CK, Delongchamp RR, Sinha RBlood determinations of S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine: correlations with dietCancer Epidemiol Biomarkers Prev.(2001 Jun)
      17.^Silveri MM, Parow AM, Villafuerte RA, Damico KE, Goren J, Stoll AL, Cohen BM, Renshaw PFS-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjectsBiol Psychiatry.(2003 Oct 15)
      22.^Woodard RW, Tsai MD, Floss HG, Crooks PA, Coward JKStereochemical course of the transmethylation catalyzed by catechol O-methyltransferaseJ Biol Chem.(1980 Oct 10)
      27.^Giulidori P, Cortellaro M, Moreo G, Stramentinoli GPharmacokinetics of S-adenosyl-L-methionine in healthy volunteersEur J Clin Pharmacol.(1984)
      30.^Horne DW, Holloway RS, Wagner CTransport of S-adenosylmethionine in isolated rat liver mitochondriaArch Biochem Biophys.(1997 Jul 15)
      32.^Pavia J, Martos F, Gonzalez-Correa JA, Garcia AJ, Rius F, Laukkonen S, de la Cuesta FSEffect of S-adenosyl methionine on muscarinic receptors in young ratsLife Sci.(1997)
      33.^Muccioli G, Scordamaglia A, Bertacco S, Di Carlo REffect of S-adenosyl-L-methionine on brain muscarinic receptors of aged ratsEur J Pharmacol.(1992 Nov 2)
      36.^Fava M, Borus JS, Alpert JE, Nierenberg AA, Rosenbaum JF, Bottiglieri TFolate, vitamin B12, and homocysteine in major depressive disorderAm J Psychiatry.(1997 Mar)
      37.^Alpert JE, Mischoulon D, Nierenberg AA, Fava MNutrition and depression: focus on folateNutrition.(2000 Jul-Aug)
      38.^Bottiglieri T, Chary TK, Laundy M, Carney MW, Godfrey P, Toone BK, Reynolds EHTransmethylation in depressionAla J Med Sci.(1988 Jul)
      39.^Matthysse S, Baldessarini RJS-adenosylmethionine and catechol-O-methyl-transferase in schizophreniaAm J Psychiatry.(1972 Apr)
      42.^Saletu-Zyhlarz GM, Anderer P, Linzmayer L, Semlitsch HV, Assandri A, Prause W, Hassan Abu-Bakr M, Lindeck-Pozza E, Saletu BVisualizing central effects of S-adenosyl-L-methionine (SAMe), a natural molecule with antidepressant properties, by pharmaco-EEG mappingInt J Neuropsychopharmacol.(2002 Sep)
      44.^Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GPRapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methioninePsychiatry Res.(1995 Apr 28)
      45.^Berlanga C, Ortega-Soto HA, Ontiveros M, Senties HEfficacy of S-adenosyl-L-methionine in speeding the onset of action of imipraminePsychiatry Res.(1992 Dec)
      48.^Alpert JE, Papakostas G, Mischoulon D, Worthington JJ 3rd, Petersen T, Mahal Y, Burns A,Bottiglieri T, Nierenberg AA, Fava MS-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxineJ Clin Psychopharmacol.(2004 Dec)
      50.^Strous RD, Nolan KA, Lapidus R, Diaz L, Saito T, Lachman HMAggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: a replication studyAm J Med Genet B Neuropsychiatr Genet.(2003 Jul 1)
      52.^Di Rocco A, Rogers JD, Brown R, Werner P, Bottiglieri TS-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trialMov Disord.(2000 Nov)
      55.^Spijkerman AM, Smulders YM, Kostense PJ, Henry RM, Becker A, Teerlink T, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CDS-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn StudyArterioscler Thromb Vasc Biol.(2005 Apr)
      57.^Mischoulon D, Alpert JE, Arning E, Bottiglieri T, Fava M, Papakostas GIBioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorderJ Clin Psychiatry.(2012 Jun)
      58.^Gören JL, Stoll AL, Damico KE, Sarmiento IA, Cohen BMBioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humansPharmacotherapy.(2004 Nov)
      59.^Tavoni A, Vitali C, Bombardieri S, Pasero GEvaluation of S-adenosylmethionine in primary fibromyalgia. A double-blind crossover studyAm J Med.(1987 Nov 20)
      60.^Volkmann H, Nørregaard J, Jacobsen S, Danneskiold-Samsøe B, Knoke G, Nehrdich DDouble-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgiaScand J Rheumatol.(1997)
      61.^Jacobsen S, Danneskiold-Samsøe B, Andersen RBOral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluationScand J Rheumatol.(1991)
      62.^Goldenberg DLPharmacological treatment of fibromyalgia and other chronic musculoskeletal painBest Pract Res Clin Rheumatol.(2007 Jun)
      63.^Kalhan SC, Edmison J, Marczewski S, Dasarathy S, Gruca LL, Bennett C, Duenas C, Lopez RMethionine and protein metabolism in non-alcoholic steatohepatitis: evidence for lower rate of transmethylation of methionineClin Sci (Lond).(2011 Aug)
      64.^Loguercio C, Nardi G, Argenzio F, Aurilio C, Petrone E, Grella A, Del Vecchio Blanco C, Coltorti MEffect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver diseaseAlcohol Alcohol.(1994 Sep)
      65.^Chawla RK, Lewis FW, Kutner MH, Bate DM, Roy RG, Rudman DPlasma cysteine, cystine, and glutathione in cirrhosisGastroenterology.(1984 Oct)
      66.^Yuan L, Kaplowitz NGlutathione in liver diseases and hepatotoxicityMol Aspects Med.(2009 Feb-Apr)
      67.^Mato JM, Cámara J, Fernández de Paz J, Caballería L, Coll S, Caballero A, García-Buey L, Beltrán J, Benita V, Caballería J, Solà R, Moreno-Otero R, Barrao F, Martín-Duce A, Correa JA, Parés A, Barrao E, García-Magaz I, Puerta JL, Moreno J, Boissard G, Ortiz P, Rodés JS-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trialJ Hepatol.(1999 Jun)
      68.^Santini D, Vincenzi B, Massacesi C, Picardi A, Gentilucci UV, Esposito V, Liuzzi G, La Cesa A, Rocci L, Marcucci F, Montesarchio V, Groeger AM, Bonsignori M, Tonini GS-adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injuryAnticancer Res.(2003 Nov-Dec)
      70.^Roncaglia N, Locatelli A, Arreghini A, Assi F, Cameroni I, Pezzullo JC, Ghidini AA randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasisBJOG.(2004 Jan)
      75.^Duong FH, Filipowicz M, Tripodi M, La Monica N, Heim MHHepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2AGastroenterology.(2004 Jan)
      78.^Feld JJ, Modi AA, El-Diwany R, Rotman Y, Thomas E, Ahlenstiel G, Titerence R, Koh C, Cherepanov V, Heller T, Ghany MG, Park Y, Hoofnagle JH, Liang TJS-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonrespondersGastroenterology.(2011 Mar)
      79.^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)
      82.^Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BMSafety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritisJ Fam Pract.(2002 May)
      86.^Manteuffel-Cymborowska M, Chmurzynska W, Grzelakowska-Sztabert BTissue-specific effects of testosterone on S-adenosylmethionine formation and utilization in the mouseBiochim Biophys Acta.(1992 Apr 22)
      87.^Heljasvaara R, Veress I, Halmekytö M, Alhonen L, Jänne J, Laajala P, Pajunen ATransgenic mice overexpressing ornithine and S-adenosylmethionine decarboxylases maintain a physiological polyamine homoeostasis in their tissuesBiochem J.(1997 Apr 15)
      92.^Kagan BL, Sultzer DL, Rosenlicht N, Gerner RHOral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trialAm J Psychiatry.(1990 May)