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S-Adenosylmethionine (SAMe)

Nutrient Name: S-adenosylmethionine (SAMe).
Synonyms: S-adenosyl-L-methionine, S-adenosyl methionine, ademetionine; AdoMet.

Summary Table
nutrient description

Chemistry and Forms

Sulfuradenosylmethionine, S-adenosyl-L-methionine; S-adenosylmethionine butanedisulfonate, S-adenosylmethionine tosylate.

Physiology and Function

S-Adenosylmethionine (SAMe) is a naturally occurring compound functioning in a multitude of biochemical reactions and biosynthetic processes throughout the central nervous system (CNS), liver, connective tissue, and detoxification systems and within cellular metabolic activities. Dietary methionine is primarily metabolized in the liver, where it is combined with adenosine triphosphate (ATP) to form SAMe in a reaction catalyzed by methionine adenosyltransferase I/III (MAT I/III), the product of the MAT1A gene, which is exclusively expressed in the liver. SAMe serves as a precursor molecule to three main metabolic pathways within all cells: methylation, transulfuration, and aminopropylation.

S-Adenosylmethionine is the body's main biological methyl donor. After donating a methyl group in the synthesis of nucleic acids (DNA and RNA), choline, creatine, carnitine, proteins, phospholipids, catecholamines, epinephrine, and various neurotransmitters, SAMe is converted to S-adenosylhomocysteine (SAH). Subsequent trans-sulfuration reactions enable and regulate formation of sulfur-containing amino acids such as cysteine, glutathione, and taurine. After donating sulfur in this way, SAH gives up adenosine and is rapidly metabolized to homocysteine. Through the pathway known as aminopropylation, SAMe is metabolized to decarboxylated SAMe and functions as a cofactor in the synthesis of polyamines, including spermidine, puescine, and spermine, which are essential for cellular growth and differentiation, gene expression, DNA repair, protein phosphorylation, and neuron myelination and regeneration. As a key facilitator of phosphatidylcholine synthesis, SAMe plays a role in promoting flexible and responsive cellular membranes and supports healthy bile production and flow. SAMe influences levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, and homovanillic acid, a dopamine metabolite, in the cerebrospinal fluid (CSF) and appears to cross the blood-brain barrier via carrier-mediated transport.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Human clinical trials investigating SAMe have reported positive outcomes in the treatment of a range of conditions, reflecting the broad and diverse functions of this substance in human physiology. In particular, researchers have focused on depression, osteoarthritis, and liver disorders. Although a number of studies have shown clinical benefit, most have been limited by small numbers, brief duration, and preliminary or flawed design. Further, the research findings from human trials cannot be extrapolated readily to self-prescribed use or typical clinical practice, since oral dosages in European clinical trials have usually been significantly higher than those typically used by many individuals, and many studies have used intravenous (IV) or intramuscular (IM) modes of administration.

Historical/Ethnomedicine Precedent

S-Adenosylmethionine has not been used historically as an isolated nutrient.

Possible Uses

Alzheimer's disease, attention deficit–hyperactivity disorder (ADHD), cardiovascular disease, cirrhosis, dementia, depression, fibromyalgia, Gilbert's syndrome, infertility (male), insomnia, intrahepatic cholestasis of pregnancy, migraine, osteoarthritis, rheumatoid arthritis, Sjögren's syndrome, vacuolar myelopathy.

Dietary Sources

Methionine, from which SAMe is formed, can be obtained from a variety of dietary sources, but SAMe itself is not available through foods in any significant amounts. Dietary deficiencies in methionine, folate, or vitamin B12can reduce SAMe levels.

Nutrient Preparations Available

S-Adenosylmethionine butanedisulfonate, S-adenosylmethionine tosylate.

In Europe, pharmaceutical preparations of SAMe are available mainly as IV, IM, and oral forms. In the United States, SAMe is primarily available in an over-the-counter (OTC) nutraceutical oral form as a capsule or tablet. SAMe is extremely hygroscopic and highly unstable; enteric-coated tablets packaged in foil or foil blister packs are considered the most stable form to avoid degradation.

Dosage Forms Available

Enteric-coated tablets. Parenteral preparations are available in Europe.

Source Materials for Nutrient Preparations

Biofermentation or synthesis from adenosine and methionine, generally complexed with a stabilizing salt, such as tosylate, disulfate tosylate, disulfate ditosylate, or 1,4-butanedisulfonate.

Dosage Range


Dietary: Not applicable.

  • Estimated safe and adequate daily dietary intake: Not applicable.
  • Average U.S. daily intake: Not applicable.
  • Recommended dietary allowance (RDA): None established.

Supplemental/Maintenance: Not applicable.

Pharmacological/Therapeutic: 400 mg three or four times daily, based on clinical trials.

Oral: 200 to 1600 mg daily.

Adequate dose-escalation studies using the oral formulation of SAMe have yet to be performed to demonstrate the most effective oral dose of SAMe.

The most common dosage is 400 mg daily, even though this level is significantly below the efficacy threshold indicated by research and clinical experience. Its relatively high cost has often been considered a limiting factor in the effective use of SAMe as a nutraceutical, especially when self-prescribed.

Toxic: No dietary reference intake (DRI) has been set for S-adenosylmethionine.

Pediatric (<18 Years)

No guidelines have been established for therapeutic or toxic dosage levels of SAMe for infants or children. Use within such populations is not usually recommended as appropriate.

Laboratory Values

Plasma levels of SAMe. Levels ofL-methionine S-adenosyltransferase activity in erythrocytes, SAMe concentrations in CSF, and concentrations of SAMe and S-adenosylhomocysteine (SAH) in whole blood have also been used in clinical trials.

safety profile


In clinical trials and reported clinical use, SAMe has generally been well tolerated and considered safe.

Nutrient Adverse Effects

No toxic effects have been reported in research or clinical experience involving SAMe. Dry mouth, nausea, restlessness, and skin rashes are among the several minor adverse effects occasionally associated with SAMe intake and generally reported at higher doses. One case report of “serotonin syndrome” involving concomitant use of IM SAMe (100 mg/day) and clomipramine (75 mg/day) represents the most severe adverse event known. 1-4


Mutagenicity: Research thus far indicates that SAMe is nonmutagenic in vitro and in vivo, even using high doses.

Adverse Effects Among Specific Populations

S-Adenosylmethionine use may trigger a manic episode in individuals with bipolar disorder. 5-7

Pregnancy and Nursing

The safety of SAMe use in pregnant or breast-feeding women has not been established. However, several studies investigating SAMe in the treatment of intrahepatic cholestasis of pregnancy (ICP) have reported the agent as apparently safe during pregnancy.

Infants and Children

The safety of SAMe administration in infants and children has not been established.


Bipolar disorder, migraines, Parkinson's disease; individuals with active bleeding.

Precautions and Warnings

Given that SAMe is a precursor to homocysteine and that methionine may elevate homocysteine, it would be prudent to assess homocysteine levels before treating with SAMe in individuals with a significant family history of coronary heart disease.

interactions review

Strategic Considerations

S-Adenosylmethionine's central role in several critical metabolic pathways indicates that both excessive intake and drug-induced depletion are likely to produce significant consequences. Well-designed studies will be required to clarify and articulate the particulars of these patterns in a systematic manner. Likewise, further research is needed to determine therapeutic approaches to synergistic use of SAMe as part of integrative therapeutics employing the nutraceutical in conjunction with various conventional therapies for treatment of the conditions for which SAMe shows promise.

The issue of SAMe use by individuals diagnosed with bipolar disorder continues to be controversial; well-designed research is needed to assess its efficacy as a therapeutic agent, alone or in conjunction with conventional pharmacological treatments.

The scientific understanding of the physiology and pharmacology of SAMe is generally in a preliminary state, particularly with regard to genetic variability and its pharmacogenomic implications. In particular, the critical roles of SAMe in the areas of DNA methylation, neurotransmitter self-regulatory processes, and hepatic conjugation of pharmaceutical agents all deserve continued research and will undoubtedly reveal significant implications for SAMe's therapeutic application and interactions with other medications. Recent clinical trial data suggest that SAMe appears to augment the antidepressant effect of SSRI and SSRI/SNRI agents. Large, randomized, placebo-controlled trials addressing the difficult clinical problem of antidepressant-refractory depression are warranted.

nutrient-drug interactions
Imipramine and Other Tricyclic Antidepressants
Levodopa and Related Antiparkinsonian Medications
Oral Contraceptives: Monophasic, Biphasic, and Triphasic Estrogen Preparations (Synthetic Estrogen and Progesterone Analogs)
Ursodeoxycholic Acid and Chenodeoxycholic Acid
Evidence: Ursodeoxycholic acid (UDCA, ursodiol; Actigall, Destolit, Urdox, Urso, Ursofalk, Ursogal). Extrapolated, based on similar properties: Chenodeoxycholic acid (CDCA, chenodiol; Chenix).
Beneficial or Supportive Interaction, with Professional Management

Probability: 2. Probable
Evidence Base: Emerging

Effect and Mechanism of Action

Ursodeoxycholic acid (UDCA) is used in the treatment of several hepatobiliary conditions to reduce pruritus, treat cholelithiasis, and improve biochemical parameters, particularly bile constituents. The medical use of bear gallbladder (Xiongdan)in Chinese medicine was first recorded in the Yao Xing Lun(“Treatise on the Nature of Medicinal Herbs”), a now-lost text from the Song Dynasty that originated in the early Tang Dynasty (ca. 600 CE). Currently, the material is produced synthetically or extracted from byproducts of slaughterhouses. In many respects, UDCA inhabits the intermediary zone where traditional “herbal” medicine and pharmaceuticals overlap. Within conventional practice, UDCA is considered the only therapeutic modality whose effectiveness in the treatment of ICP is supported by evidence from controlled trials. 28,31 Similarly, UDCA is used for symptomatic relief of itching in the treatment of primary sclerosing cholangitis. UDCA is also used in the treatment of primary biliary cirrhosis to improve liver biochemistry, increase survival, and delay liver transplantation. Recent research on the use of UDCA in the treatment of Huntington's disease is considered promising.

S-Adenosylmethionine exerts numerous metabolic effects within the liver that can assist detoxification functions and alter bile formation in ways that may provide an additive effect with, or alternative to, UDCA as a therapeutic agent.


In a randomized clinical trial published in 1996 involving 20 women with ICP in the last trimester of pregnancy, Floreani et al. 32 compared the effects of SAMe (1000 mg/day intramuscularly) and UDCA (450 mg/day). The treatment was continued until delivery, at least 15 days, in all women. They found that UDCA was more effective than SAMe in controlling pruritus and total bile acids. Subsequently Nicastri et al. 27 conducted a randomized placebo-controlled study involving 32 women exhibiting ICP who were divided into four groups. These researchers determined that, after treatment for 20 days, a “combination of ursodeoxycholic acid and S-adenosylmethionine is more effective than placebo and than either drug alone.” Roncaglia et al. 33 conducted a randomized controlled trial of oral UDCA (300 mg twice daily) and oral S-adenosyl- L-methionine (500 mg twice daily) in the treatment of severe gestational cholestasis. They found that women receiving UDCA demonstrated a significantly greater improvement in tests of liver function (i.e., concentration of serum bile acids, aspartate transaminase [AST], alanine transaminase [ALT], and bilirubin) compared with those receiving SAMe. Duration of therapy was significantly greater in women receiving UDCA compared with SAMe.

Nutritional Therapeutics, Clinical Concerns, and Adaptations

A relatively rare disorder, ICP appears to be related to an exaggerated genetic sensitivity to estrogens and manifests during pregnancy with pruritus and icterus as the chief complaints. Although ICP is generally considered as carrying minimal medical risk to the mother, it is regarded as presenting significant risk of perinatal mortality to the fetus, preterm delivery, fetal distress, and meconium staining. Elevated alkaline phosphatase and serum bilirubin levels are characteristic, as are other increased values of parameters indicating altered liver function and bile composition. The trend in clinical trials reveals a pattern of research focusing on the relative efficacy of UDCA and SAMe in the treatment of ICP. There is general agreement that UDCA represents a therapeutic agent supported by both clinical experience and research evidence. The available studies, although all small in size, suggest that a combination therapy provides synergistic, or at least additive, therapeutic efficacy. Given the consensus and evidence that both substances are safe during pregnancy, for both mother and fetus, such approaches deserve further research and empirical investigation. The utility of SAMe in the treatment of other conditions for which UDCA has shown efficacy has yet to be investigated in well-designed clinical trials of adequate size.

Venlafaxine and Related Selective Serotonin Reuptake Inhibitor and Serotonin-Norepinephrine Reuptake Inhibitor (SSRI and SNRI) Antidepressants
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Anticoagulant and Antiplatelet Medications
Monoamine Oxidase (MAO) Inhibitors
nutrient-nutrient interactions
5-Hydroxytryptophan (5-HTP)
Citations and Reference Literature
  • 1.Caruso I, Pietrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987;83:66-71.View Abstract
  • 2.Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 1987;83:89-94.View Abstract
  • 3.Berger R, Nowak H. A new medical approach to the treatment of osteoarthritis: report of an open phase IV study with ademetionine (Gumbaral). Am J Med 1987;83:84-88.View Abstract
  • 4.Cozens DD, Barton SJ, Clark R et al. Reproductive toxicity studies of ademetionine. Arzneimittelforschung 1988;38:1625-1629.View Abstract
  • 5.Carney MW, Chary TK, Bottiglieri T, Reynolds EH. Switch and S-adenosylmethionine. Ala J Med Sci 1988;25:316-319.View Abstract
  • 6.Carney MW, Chary TK, Bottiglieri T, Reynolds EH. The switch mechanism and the bipolar/unipolar dichotomy. Br J Psychiatry 1989;154:48-51.View Abstract
  • 7.Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147:591-595.View Abstract
  • 8.Stramentinoli G, Pezzoli C, Galli-Kienle M. Protective role of S-adenosyl-l-methionine against acetaminophen induced mortality and hepatotoxicity in mice. Biochem Pharmacol 1979;28:3567-3571.View Abstract
  • 9.Bray GP, Tredger JM, Williams R. S-Adenosylmethionine protects against acetaminophen hepatotoxicity in two mouse models. Hepatology 1992;15:297-301.View Abstract
  • 10.Corrales F, Ochoa P, Rivas C et al. Inhibition of glutathione synthesis in the liver leads to S-adenosyl-l-methionine synthetase reduction. Hepatology 1991;14:528-533.View Abstract
  • 11.Bellido I, Gomez-Luque A, Plaza A et al. S-Adenosyl-l-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat. Neurosci Lett 2002;321:110-114.View Abstract
  • 12.Pancheri P, Scapicchio P, Chiaie RD. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-l-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuropsychopharmacol 2002;5:287-294.View Abstract
  • 13.Bressa GM. S-Adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl 1994;154:7-14.View Abstract
  • 14.Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-l-methionine in speeding the onset of action of imipramine. Psychiatry Res 1992;44:257-262.View Abstract
  • 15.Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522.View Abstract
  • 16.Charlton CG, Crowell B Jr. Parkinson’s disease-like effects of S-adenosyl-l-methionine: effects of I-dopa. Pharmacol Biochem Behav 1992;43:423-431.
  • 17.Benson R, Crowell B, Hill B et al. The effects of l-dopa on the activity of methionine adenosyltransferase: relevance to I-dopa therapy and tolerance. Neurochem Res 1993;18:325-330.View Abstract
  • 18.Cheng H, Gomes-Trolin C, Aquilonius SM et al. Levels of l-methionine S-adenosyltransferase activity in erythrocytes and concentrations of S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with Parkinson’s disease. Exp Neurol 1997;145:580-585.
  • 19.Muller T, Woitalla D, Hauptmann B et al. Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson’s disease. Neurosci Lett 2001;308:54-56.
  • 20.Crowell BG Jr, Benson R, Shockley D, Charlton CG. S-Adenosyl-l-methionine decreases motor activity in the rat: similarity to Parkinson’s disease-like symptoms. Behav Neural Biol 1993;59:186-193.
  • 21.Charlton CG, Mack J. Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain: support for an excess methylation hypothesis for parkinsonism. Mol Neurobiol 1994;9:149-161.View Abstract
  • 22.Liu X, Lamango N, Charlton C. l-Dopa depletes S-adenosylmethionine and increases S-adenosyl homocysteine: relationship to the wearing-off effects. Soc Neurosci 1998;24:1469.
  • 23.Bottiglieri T. S-Adenosyl-l-methionine (SAMe): from the bench to the bedside—molecular basis of a pleiotrophic molecule. Am J Clin Nutr 2002;76:1151S-1157S.View Abstract
  • 24.Carrieri PB, Indaco A, Gentile S et al. S-Adenosylmethionine treatment of depression in patients with Parkinson’s disease: a double-blind, crossover study versus placebo. Curr Ther Res 1990;48:154-160.
  • 24a.Di Rocco A, Rogers JD, Brown R, et al. S-Adenosyl-Methionine improves depression in patients with Parkinson’s disease in an open-label clinical trial. Mov Disord 2000;15(6):1225-1229.
  • 25.Bennion LJ, Mott DM, Howard BV. Oral contraceptives raise the cholesterol saturation of bile by increasing biliary cholesterol secretion. Metabolism 1980;29:18-22.View Abstract
  • 26.Snowball S, Taylor W. Effects of short-term treatment with a combined oestrogen-progestin oral contraceptive on biliary lipids and cholesterol saturation index in young women. J Steroid Biochem 1985;22:257-261.View Abstract
  • 27.Nicastri PL, Diaferia A, Tartagni M et al. A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy. Br J Obstet Gynaecol 1998;105:1205-1207.View Abstract
  • 28.Laifer SA, Stiller RJ, Siddiqui DS et al. Ursodeoxycholic acid for the treatment of intrahepatic cholestasis of pregnancy. J Matern Fetal Med 2001;10:131-135.View Abstract
  • 29.Di Padova C, Tritapepe R, Di Padova F et al. S-Adenosyl-l-methionine antagonizes oral contraceptive-induced bile cholesterol supersaturation in healthy women: preliminary report of a controlled randomized trial. Am J Gastroenterol 1984;79:941-944.View Abstract
  • 30.Frezza M, Tritapepe R, Pozzato G, Di Padova C. Prevention of S-adenosylmethionine of estrogen-induced hepatobiliary toxicity in susceptible women. Am J Gastroenterol 1988;83:1098-1102.View Abstract
  • 31.Lengyel G, Feher R, Gardo S, Feher J. [Ursodeoxycholic acid treatment in intrahepatic cholestasis of pregnancy: a case report]. Orv Hetil 2002;143:2885-2888.View Abstract
  • 32.Floreani A, Paternoster D, Melis A, Grella PV. S-Adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial. Eur J Obstet Gynecol Reprod Biol 1996;67:109-113.View Abstract
  • 33.Roncaglia N, Locatelli A, Arreghini A et al. A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis. Bjog 2004;111:17-21.View Abstract
  • 34.Alpert JE, Papakostas G, Mischoulon D et al. S-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 venlafaxine. J Clin Psychopharmacol 2004;24:661-664.View Abstract
  • 35.De la Cruz JP, Merida M, Gonzalez-Correa JA et al. Effects of S-adenosyl-l-methionine on blood platelet activation. Gen Pharmacol 1997;29:651-655.View Abstract
  • 36.De La Cruz JP, Gonzalez-Correa JA, Martin-Aurioles E et al. Effects of S-adenosyl-l-methionine on platelet thromboxane and vascular prostacyclin. Biochem Pharmacol 1997;53:1761-1763.View Abstract
  • 37.Vidarabine (Vira-A). Med Lett Drugs Ther 1977;19:42-43.
  • 38.Cantoni GL, Aksamit RR, Kim IK. Methionine biosynthesis and vidarabine therapy. N Engl J Med 1982;307:1079.View Abstract
  • 39.Fabianowska-Majewska K, Duley JA, Simmonds HA. Effects of novel anti-viral adenosine analogues on the activity of S-adenosylhomocysteine hydrolase from human liver. Biochem Pharmacol 1994;48:897-903.View Abstract
  • .[No authors listed.] S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease: summary, evidence report/technology assessment: number 64: AHRQ publication no. 02-E033. Rockville, MD: Agency for Healthcare Research and Quality; 2002.
  • .Angelico M, Gandin C, Nistri A, et al. Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis. Scand J Clin Lab Invest 1994;54:459-464.
  • .Avila MA, Garcia-Trevijano ER, Martinez-Chantar ML, et al. S-adenosylmethionine revisited: its essential role in the regulation of liver function. Alcohol 2002;27(3):163-167. (Review)
  • .Ballerini FB, Anguera AL, Alcaraz P, et al. SAM in the management of postconcussional syndrome. Med Clin (Barc) 1983;80:161-164.
  • .Bell KM, Plon L, Bunney WE Jr, et al. S-adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry 1988;145(9):1110-1114.
  • .Bell KM, Potkin SG, Carreon D, et al. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand 1994;154(Suppl):15-18.
  • .Bellido I, Gomez-Luque A, Plaza A, et al. S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat. Neurosci Lett 2002;321(1-2):110-114.
  • .Bennion LJ, Ginsberg RL, Gernick MB, et al. Effects of oral contraceptives on the gallbladder bile of normal women. N Engl J Med 1976;294(4):189-192.
  • .Bennion LJ, Mott DM, Howard BV. Oral contraceptives raise the cholesterol saturation of bile by increasing biliary cholesterol secretion. Metabolism 1980;29(1):18-22.
  • .Berger R, Nowak H. A new medical approach to the treatment of osteoarthritis: report of an open phase IV study with ademetionine (Gumbaral). Am J Med 1987;83:84-88.
  • .Bombardieri G, Milani A, Bernardi L, et al. Effects of S-adenosyl-L-methionine (SAMe) in the treatment of Gilbert’s syndrome. Curr Ther Res 1985;37:580-585.
  • .Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside: molecular basis of a pleiotrophic molecule. Am J Clin Nutr 2002;76(5):1151S-1157S. (Review)
  • .Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-152. (Review)
  • .Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand 1994;154(Suppl):7-14.
  • .Carney MW, Edeh J, Bottiglieri T, et al. Affective illness and S-adenosyl methionine: a preliminary report. Clin Neuropharmacol 1986;9(4):379-385.
  • .Carrasco R, Perez-Mateo M, Gutierrez A, et al Effect of different doses of S-adenosyl-L-methionine on paracetamol hepatotoxicity in a mouse model. Methods Find Exp Clin Pharmacol 2000;22(10):737-740.
  • .Carretero MV, Latasa MU, Garcia-Trevijano ER, et al. Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine. Biochem Pharmacol 2001;61(9):1119-1128.
  • .Carrieri PB, Indaco A, Gentile S, et al. S-adenosylmethionine treatment of depression in patients with Parkinson’s disease: a double-blind, crossover study versus placebo. Curr Ther Res 1990;48:154-160.
  • .Caruso I, Pietrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987;83:66-71.
  • .Chiang PK. Biological effects of inhibitors of S-adenosylhomocysteine hydrolase. Pharmacol Ther 1998;77(2):115-134. (Review)
  • .Chiang PK, Gordon RK, Tal J, et al. S-Adenosylmethionine and methylation. FASEB J 1996;10:471-480. (Review)
  • .Chishty M, Reichel A, Abbott NJ, et al. S-adenosylmethionine is substrate for carrier mediated transport at the blood-brain barrier in vitro. Brain Res 2002;942(1-2):46-50.
  • .De Vanna M, Rigamonti R. Oral S-adenosyl-L-methionine in depression. Curr Ther Res 1992;52:478-485.
  • .Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr 2002;76(5):1172S-1176S.
  • .Detich N, Hamm S, Just G, et al. The methyl donor S-adenosylmethionine inhibits active demethylation of DNA: a candidate novel mechanism for the pharmacological effects of S-adenosylmethionine. J Biol Chem 2003;278(23):20812-20820.
  • .Di Rocco A, Rogers JD, Brown R, et al. S-adenosyl-methionine improves depression in patients with Parkinson’s disease in an open-label clinical trial. Mov Disord 2000;15(6):1225-1229.
  • .Domljan Z, Vrhovac B, Durrigl T, et al. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 1989;27:329-333.
  • .Evans PJ, Whiteman M, Tredger JM, et al. Antioxidant properties of S-adenosyl-L-methionine: a proposed addition to organ storage fluids. Free Radic Biol Med 1997;23(7):1002-1008.
  • .Fava M, Giannelli A, Rapisarda V, et al. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl- L-methionine. Psychiatry Res 1995;56(3):295-297.
  • .Fava M, Rosenbaum JF, MacLaughlin R, et al. Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant. J Psychiatr Res 1990;24:177-184.
  • .Fetrow CW, Avila JR. Efficacy of the dietary supplement S-adenosyl-L-methionine. Ann Pharmacother 2001;35(11):1414-1425.
  • .Fugh-Berman A, Cott JM. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med 1999;61(5):712-728. (Review)
  • .Gatto G, Caleri D, Michelacci S, et al. Analgesizing effect of a methyl donor (S-adenosylmethionine) in migraine: an open clinical trial. Int J Clin Pharmacol Res 1986;6:15-17.
  • .Glorioso S, Todesco S, Mazzi A, et al. Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 1985;5:39-49.
  • .Harmand MF, Vilamitjana J, Maloche E, et al. Effects of S-adenosylmethionine on human articular chondrocyte differentiation: an in vitro study. Am J Med 1987;83(Suppl 5A):48-54.
  • .Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia: double-blind clinical evaluation. Scand J Rheumatol 1991;20:294-302.
  • .Kagan BL, Sultzer DL, Rosenlicht N, et al. Oral S-adenosyl-methionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147:591-595.
  • .Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 1987;83:89-94.
  • .Lieber CS. Herman Award lecture, 1993: a personal perspective on alcohol, nutrition, and the liver. Am J Clin Nutr 1993;58:430-442. (Review)
  • .Lieber CS. S-adenosyl-L-methionine: its role in the treatment of liver disorders. Am J Clin Nutr 2002;76(5):1183S-1187S. (Review)
  • .Lieber CS, Packer L. S-Adenosylmethionine: molecular, biological, and clinical aspects: an introduction. Am J Clin Nutr 2002;76(5):1148S-1150S. (Review)
  • .Loehrer FM, Angst CP, Haefeli WE, et al. Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease. Arterioscler Thromb Vasc Biol 1996;16:727-733.
  • .Loenen WA. S-adenosylmethionine: jack of all trades and master of everything? Biochem Soc Trans 2006;34(Pt 2):330-333. (Review)
  • .Maccagno A. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 1987;83(Suppl 5A):72-77.
  • .Marcolongo R, Giordano N, Colombo B, et al. Double-blind multicentre study of the activity of s-adenosyl-methionine in hip and knee osteoarthritis. Curr Ther Res 1985;37:82-94.
  • .Martinez-Chantar ML, Garcia-Trevijano ER, Latasa MU, et al. Importance of a deficiency in S-adenosyl-L-methionine synthesis in the pathogenesis of liver injury. Am J Clin Nutr 2002;76(5):1177S-1182S. (Review)
  • .Mato JM, Cámara J, Fernández J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999;30:1081-1089.
  • .Miccoli L, Porro V, Bertolino A. Comparison between the antidepressant activity and of S- adenosylmethionine (SAMe) and that of some tricyclic drugs. Acta Neurol (Napoli) 1978;33 (3):243-255.
  • .Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence Am J Clin Nutr 2002;76(5):1158S-1161S. (Review)
  • .Montrone F, Fumagalli M, Sarzi Puttini P, et al. Double-blind study of S-adenosyl-methionine versus placebo in hip and knee arthrosis. Clin Rheumatol 1985;4:484-485.
  • .Muller T, Woitalla D, Hauptmann B, et al. Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson’s disease. Neurosci Lett 2001;308(1):54-56.
  • .Muscettola G, Galzenati M, Balbi A. SAMe versus placebo: a double blind comparison in major depressive disorders. Adv Biochem Psychopharmacol 1982;32:151-156.
  • .Nguyen M, Gregan A. S-adenosylmethionine and depression. Aust Fam Physician 2002;31(4):339-343. (Review)
  • .Osman E, Owen JS, Burroughs AK. S-adenosyl-L-methionine: a new therapeutic agent in liver disease? Aliment Pharmacol Ther 1993;7:21-28. (Review)
  • .Pancheri P, Scapicchio P, Chiaie RD. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuropsychopharmacol 2002;5(4):287-294.
  • .Piacentino R, Malara D, Zaccheo F, et al. Preliminary study of the use of s. adenosyl methionine in the management of male sterility. Minerva Ginecol 1991;43:191-193. [Italian]
  • .Pies R. Adverse neuropsychiatric reactions to herbal and over-the-counter "antidepressants." J Clin Psychiatry 2000;61(11):815-820. (Review)
  • .Poirier LA, Wise CK, Delongchamp RR, et al. Blood determinations of S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine: correlations with diet. Cancer Epidemiol Biomarkers Prev 2001;10(6):649-655.
  • .Richardson B. Impact of aging on DNA methylation. Ageing Res Rev 2003;2:3:245-261.
  • .Saletu B, Anderer P, Di Padova C, et al. Electrophysiological neuroimaging of the central effects of S-adenosyl-L-methionine by mapping of electroencephalograms and event-related potentials and low-resolution brain electromagnetic tomography. Am J Clin Nutr 2002;76(5):1162S-1171S.
  • .Saletu B, Anderer P, Linzmayer L, et al. Pharmacodynamic studies on the central mode of action of S-adenosyl-L-methionine (SAMe) infusions in elderly subjects, utilizing EEG mapping and psychometry. J Neural Transm 2002;109(12):1505-1526.
  • .Salmaggi P, Bressa GM, Nicchia G, et al. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom 1993;59(1):34-40.
  • .Schumacher HR. Osteoarthritis: the clinical picture, pathogenesis, and management with studies on a new therapeutic agent, S-adenosylmethionine. Am J Med 1987;83(Suppl 5A):1-4. (Review)
  • .Stramentinoli G, Di Padova C, Gualano M, et al. Ethynylestradiol-induced impairment of bile secretion in the rat: protective effects of S-adenosyl-L-methionine and its implication in estrogen metabolism. Gastroenterology 1981;80(1):154-158.
  • .Tavoni A, Jeracitano G, Cirigliano G. Evaluation of S-adenosylmethionine in secondary fibromyalgia: a double-blind study. Clin Exp Rheumatol 1998;16:106-107. (Letter)
  • .Tavoni A, Vitali C, Bombardieri S, et al. Evaluation of S-adenosylmethionine in primary fibromyalgia: a double-blind crossover study. Am J Med 1987;83(Suppl 5A):107-110.
  • .Turner MA, Yang X, Yin D, et al. Structure and function of S-adenosylhomocysteine hydrolase. Cell Biochem Biophys 2000;33(2):101-125. (Review)
  • .Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83(Suppl 5A):78-80.
  • .Volkmann H, Norregaard J, Jacobsen S, et al. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scand J Rheumatol 1997;26:206-211.