What is it?
SAMe is a chemical that is found naturally in the body. It can also be made in the laboratory.
SAMe has been available as a dietary supplement in the US since 1999, but it has been used as a prescription drug in Italy since 1979, in Spain since 1985, and in Germany since 1989. Researchers discovered the potential usefulness of SAMe for treating osteoarthritis by accident. They were studying SAMe’s effect on depression when the patients they were following reported an unexpected improvement in their osteoarthritis symptoms.
SAMe is used for depression, anxiety, heart disease, fibromyalgia, osteoarthritis, bursitis, tendonitis, chronic lower back pain, dementia, Alzheimer's disease, slowing the aging process, chronic fatigue syndrome (CFS), improving intellectual performance, liver disease, and Parkinson's disease. It is also used for attention deficit-hyperactivity disorder (ADHD), multiple sclerosis, spinal cord injury, seizures, migraine headache, and lead poisoning.
Some women use SAMe for premenstrual syndrome (PMS) and a more severe form of PMS called premenstrual dysphoric disorder (PMDD).
How effective is it?
Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.
The effectiveness ratings for SAMe are as follows:
Likely effective for...
- Osteoarthritis. Taking SAMe by mouth seems to work about as well as aspirin and similar drugs, but it can take twice as long to start working. Most people with arthritis need to take SAMe for about a month before they feel better.
- Depression. Taking SAMe by mouth or by injection seems to reduce symptoms of depression. Several studies have shown that SAMe can be beneficial and might be as effective as some prescription medications used for depression (tricyclic antidepressants). Some research also shows that taking SAMe might be helpful for people who don’t have a good response to a prescription antidepressant. But keep in mind, SAMe should not be taken in combination with a prescription antidepressant without the monitoring of a health professional.
Possibly effective for...
- Some symptoms of AIDS-related nerve problems.
- Decreased bile flow from the liver to the gallbladder.
Insufficient evidence to rate effectiveness for...
- Attention deficit-hyperactivity disorder (ADHD). Limited research suggests SAMe might lessen ADHD symptoms in adults.
- Alcohol-related liver disease. Research studies to date do not agree on the effectiveness of SAMe for liver disease.
- Heart disease.
- Chronic low back pain.
- Improving intelligence.
- Premenstrual syndrome (PMS).
- Premenstrual dysphoric disorder (PMDD).
- Chronic fatigue syndrome (CFS).
- Multiple sclerosis.
- Spinal cord injury.
- Migraine headache.
- Other conditions.
More evidence is needed to rate SAMe for these uses.
The body uses SAMe to make certain chemicals in the body that play a role in pain, depression, liver disease, and other conditions. People who don’t make enough SAMe naturally may be helped by taking SAMe as a supplement.
SAMe is LIKELY SAFE for most people. It can sometimes cause gas, vomiting, diarrhea, constipation, dry mouth, headache, mild insomnia, anorexia, sweating, dizziness, and nervousness, especially at higher doses. It can make some people with depression feel anxious.
Special precautions & warnings:
Pregnancy and breast-feeding: Not enough is known about the safety of using SAMe during pregnancy and breast-feeding. Stay on the safe side and avoid use.
Bipolar disorder: Use of SAMe can cause people with bipolar disorder to convert from depression to mania.
Parkinson’s disease: SAMe might make Parkinson’s symptoms worse.
Surgery: SAMe might affect the central nervous system. This could interfere with surgery. Stop taking SAMe at least 2 weeks before a scheduled surgery.
Do not take this combination.
Dextromethorphan (Robitussin DM, and others)
SAMe can affect a brain chemical called serotonin. Dextromethorphan (Robitussin DM, others) can also affect serotonin. Taking SAMe along with dextromethorphan (Robitussin DM, others) might cause too much serotonin in the brain and serious side effects including heart problems, shivering, and anxiety. Do not take SAMe if you are taking dextromethorphan (Robitussin DM, and others).
Medications for depression (Antidepressant drugs)
SAMe increases a brain chemical called serotonin. Some medications for depression also increase the brain chemical serotonin. Taking SAMe along with these medications for depression might increase serotonin too much and cause serious side effects including heart problems, shivering, and anxiety. Do not take SAMe if you are taking medications for depression.
Some of these medications for depression include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Tofranil), and others.
Medications for depression (MAOIs)
SAMe increases a chemical in the brain. This chemical is called serotonin. Some medications used for depression also increase serotonin. Taking SAMe along with these medications used for depression might cause too much serotonin in the body, and serious side effects including heart problems, shivering, and anxiety.
Some of these medications used for depression include phenelzine (Nardil), tranylcypromine (Parnate), and others.
Be cautious with this combination.
Levodopa is used for Parkinson's disease. SAMe can chemically change levodopa in the body and decrease the effectiveness of levodopa. Taking SAMe along with levodopa might make Parkinson's disease symptoms worse. Do not take SAMe if you are taking levodopa.
SAMe increases a chemical in the brain called serotonin. Meperidine (Demerol) can also increase serotonin in the brain. Taking SAMe along with meperidine (Demerol) might cause too much serotonin in the brain and serious side effects including heart problems, shivering, and anxiety.
SAMe increases a brain chemical called serotonin. Pentazocine (Talwin) also increases serotonin. Taking SAMe along with pentazocine (Talwin) might cause serious side effects including heart problems, shivering, and anxiety. Do not take SAMe if you are taking pentazocine (Talwin).
Tramadol (Ultram) can affect a chemical in the brain called serotonin. SAMe can also affect serotonin. Taking SAMe along with tramadol (Ultram) might cause too much serotonin in the brain and side effects including confusion, shivering, stiff muscles, and other side effects.
Herbs and supplements with serotonergic properties
SAMe increases a chemical in the brain called serotonin. Taking SAMe along with other herbs and supplements that increase serotonin might lead to too much serotonin and cause serious side effects including heart problems, shivering and anxiety, Herbs and supplements that increase serotonin levels include 5-HTP, Hawaiian baby woodrose, L-tryptophan, and St. John's wort.
There are no known interactions with foods.
The following doses have been studied in scientific research:
- For depression: 400-1600 mg per day.
- For osteoarthritis: 200 mg three times daily.
- For fibromyalgia: 800 mg per day.
Ademetionine, Adenosylmethionine, Adénosylméthionine, S-Adenosyl Methionine, S-Adénosyl Méthionine, S-Adenosyl-L-Methionine, S-Adénosyl-L-Méthionine, S-Adenosylmethionine, S-Adénosylméthionine, S-Adenosylmethionine Butanedisulfonate, S-Adenosylmethionine Tosylate, S-Adenosylmethionine Tosylate Disulfate, SAM, SAM-e, Sammy.
To learn more about how this article was written, please see the Natural Medicines Comprehensive Database methodology.methodology (http://www.nlm.nih.gov/medlineplus/druginfo/natural/methodology.html).
To see all references for the SAMe page, please go to http://www.nlm.nih.gov/medlineplus/druginfo/natural/786.html.
- Work Group for Major Depressive Disorder. Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition. American Psychiatric Association, May 2010 (Published October 2010). Available at: http://www.psych.org/guidelines/mdd2010.
- Papakostas GI, Mischoulon D, Shyu I, et al. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry 2010;167:942-8.
- Ravindran AV, Lam RW, Filteau MJ, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. V. Complementary and alternative medicine treatments. J Affect Disord 2009;117 Suppl 1:S54-64.
- Nelson JC. S-adenosyl methionine (SAMe) augmentation in major depressive disorder. (Editorial). Am J Psychiatry 2010;167:889-91.
- Arnold O, Saletu B, Anderer P, et al. Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry. Eur Neuropsychopharmacol 2005;15:533-43.
- Rambaldi A, Gluud C. S-adenosyl-L-methionine for alcoholic liver diseases. Cochrane Database Syst Rev 2006;:CD002235.
- Aggarwal R, Sentz J, Miller MA. Role of zinc administration in prevention of childhood diarrhea and respiratory illnesses: a meta-analysis. Pediatrics 2007;119:1120-30.
- Goren JL, Stoll AL, Damico KE, et al. Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans. Pharmacotherapy 2004;24:1501-7.
- Najm WI, Reinsch S, Hoehler F, et al. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind crossover trial. BMC Musculoskelet Disord 2004;5:6.
- Charlton CG, Crowell B Jr. Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav 1992;43:423-31.
Purohit V, Russo D. Role of S-adenosyl-L-methionine in the treatment of alcoholic liver disease: introduction and summary of the symposium. Alcohol 2002;27:151-4.
- Shekim WO, Antun F, Hanna GL, et al. S-adenosyl-L-methionine (SAM) in adults with ADHD, RS: preliminary results from an open trial. Psychopharmacol Bull 1990;26:249-53.
- Lieber CS. S-Adenosyl-L-methionine: its role in the treatment of liver disorders. Am J Clin Nutr 2002;76:1183S-17S.
- 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;76:1177S-82S.
- Saletu B, Anderer P, Di Padova C. 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;76:1162S-71S.
- 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;76:1158S-61S.
- Lieber CS, Packer L. S-Adenosylmethionine: molecular, biological, and clinical aspects—an introduction. Am J Clin Nutr 2002;76:1148S-50S.
- Soeken KL, Lee WL, Bausell RB, et al. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract 2002;51:425-30.
- 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-7S.
- Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-Lmethionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in multicenter studies. Am J Clin Nutr 2002;76:1172S-6S.
- Hardy M, Coulter I, Morton SC, et al. S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease. Evidence Report/Technology Assessment Number 64. Agency for Healthcare Research and Quality, US Dept of Health and Human Services; 2002. AHRQ publication 02-E033. Rockville, Md. Available at: http://www.ahrq.gov/clinic/tp/sametp.htm.
- Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3.
- Czap A. Beware the son of SAMe. Altern Med Rev 1999;4:73.
- Cowley G, Underwood A. Newsweek. July 5, 1999; pp. 46-50.
- Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol 1991;20:294-302.
- Frezza M, Centini G, Cammareri G, et al. S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepatogastroenterology 1990;37:122-5.
- Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology 1990;99:211-5.
- Podymova SD, Nadinskaia M. [Clinical trial of heptral in patients with chronic diffuse liver disease with intrahepatic cholestasis syndrome]. Klin Med (Mosk) 1998;76:45-8.
- Loguercio C, Nardi G, Argenzio F, et al. Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease. Alcohol 1994;29:597-604.
- Diaz BA, Dominguez HR, Uribe AF. Parenteral S-adenosylmethionine compared to placebos in the treatment of alcoholic liver diseases. An Med Interna 1996;13:9-15.
- Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52.
- Friedel HA, Goa KL, Benfield P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 1989;38:389-416.
- 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;26:206-11.
- Almasio P, Bortolini M, Pagliaro L, Coltorti M. Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis. Drugs 1990;40:111-23.
- Tan SV, Guiloff RJ. Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS. J Neurol Neurosurg Psychiatry 1998;65:23-8.
- Castagna A, Le Grazie C, Accordini A, et al. Cerebrospinal fluid S-adenosylmethionine (SAMe) and glutathione concentrations in HIV infection: effect of parenteral treatment with SAMe. Neurol 1995;45:1678-83.
- Lipinski JF, Cohen BM, Frankenburg F, et al. Open trial of S-adenosylmethionine for treatment of depression. Am J Psychiatry 1984;141:448-50.
- 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.
- Laudanno OM. Cytoprotective effect of S-adenosylmethionine compared with that of misoprostol against ethanol-, aspirin-, and stress-induced gastric damage. Am J Med 1987;83(5A):43-7.
- Tavoni A, Vitali C, Bombardieri S, Pasero G. Evaluation of S-adenosylmethionine in primary fibromyalgia. A double-blind crossover study. Am J Med 1987;83:107-10.
- di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med 1987;83:60-5.
- 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.
- Maccagno A, Di Giorgio EE, Caston OL, Sagasta CL. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 1987;83:72-7.
- Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83:78-80.
- Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987;83:81-3.
- 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;83:84-8.
- Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 1987;83:89-94.
- Baldessarini RJ. Neuropharmacology of S-adenosyl-L-methionine. Am J Med 1987;83:95-103.
- Vahora SA, Malek-Ahmasi P. S-adenosylmethionine in the treatment of depression. Neurosci Biobehav Rev 1988;12:139-41.
- Bell KM, Plon L, Bunney WE Jr, Potkin SG. S-adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry 1988;145:1110-4.
- Domljan Z, Vrhovac B, Durrigl T, Pucar I. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 1989;27:329-33.
- Chawla RK, Bonkovsky HL, Galambos JT. Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. Drugs 1990;40:98-110.
- Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432-6.
- Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147:591-5.
- 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;44:257-62.
- 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;59:34-40.
- Bell KM, Potkin SG, Carreon D, Plon L. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl 1994;154:15-8.
- Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl 1994;154:7-14.
- Bradley JD, Flusser D, Katz BP, et al. A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis. J Rheumatol 1994;21:905-11.
- Fava M, Giannelli A, Rapisarda V, et al. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. Psychiatry Res 1995;56:295-7.
- Gaster B. S-adenosylmethionine (SAMe) for treatment of depression. Alternative Medicine Alert, 1999;12:133-5.
- Carney MW, Chary TK, Bottiglieri T, Reynolds EH. The switch mechanism and the bipolar/unipolar dichotomy. Br J Psychiatry 1989;154:48-51.
- Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522.
- De Vanna M, Rigamonti R. Oral S-adenosyl-L-methionine in depression. Curr Ther Res 1992;52:478-85.
- Janicak PG, Lipinski J, Davis JM, et al. S-adenosylmethionine in depression. A literature review and preliminary report. Ala J Med Sci 1988;25:306-13.
- Stramentinoli G, Gualano M, Galli-Kienle M. Intestinal absorption of S-adenosyl-L-methionine. J Pharmacol Exp Ther 1979;209:323-6.
- Investigator's Brochure: Ademetionine 1,4-butanedisulfonate. Knoll Pharmaceuticals.
- 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;16:727-33.
- Loehrer FM, Schwab R, Angst CP, et al. Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans. J Pharmacol Exp Ther 1997;22:845-50.
- Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999;30:1081-9.
- Perna AF, Castaldo P, Ingrosso D, et al. Homocysteine, a new cardiovascular risk factor, is also a powerful uremic toxin. J Nephrol 1999;12:230-40.
- FDA. List of orphan designations and approvals. Office of Orphan Products Development. Available at: www.fda.gov/orphan/designat/list.htm.
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