- What other names is SAMe known by?
- What is SAMe?
- Is SAMe effective?
- How does SAMe work?
- Are there safety concerns?
- Are there any interactions with medications?
- Dosing considerations for SAMe.
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.
SAMe is a molecule that is formed naturally in the body. It can also be made in the laboratory. SAMe is involved in the formation, activation, or breakdown of other chemicals in the body, including hormones, proteins, phospholipids, and certain drugs.
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.
SAMe is used by mouth for depression, anxiety, heart disease, fibromyalgia, abdominal pain, osteoarthritis, bursitis, tendonitis, chronic lower back pain, dementia, Alzheimer's disease, slowing the aging process, chronic fatigue syndrome (CFS), improving mental 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, lead poisoning, to break down a chemical in the body called bilirubin, or to help with disorders related to the buildup of a chemical called porphyrin or its precursors.
SAMe is used intravenously (by IV) for depression, osteoarthritis, AIDS-related nervous system disorders, fibromyalgia, liver disease, cirrhosis, and for a liver disorder that occurs in pregnant women called intrahepatic cholestasis.
SAMe can relieve pain and some of the other symptoms of osteoarthritis about as well as aspirin and similar drugs, but it may take twice as long to work. Most people with arthritis need to take SAMe for about a month before they feel better.
SAMe also seems to help protect the liver. People with liver disease in the early stages sometimes do better when they take SAMe and might even be able to delay the need for a liver transplant. But people with advanced liver disease are not as likely to be helped by taking SAMe.
There isn't enough information to know if SAMe is effective for the other conditions that people use it for, including: heart disease, bursitis, tendonitis, chronic low back pain, improving intelligence, staying young, multiple sclerosis, spinal cord injury, seizures, migraine headache, and others.
Likely Effective for...
- Depression. Taking SAMe by mouth, as an injection, or as a shot seems to reduce symptoms of major depression. Several studies have shown that taking SAMe by mouth can be beneficial and might be as effective as some prescription medications used for depression (tricyclic antidepressants). Some research also shows that taking SAMe by mouth might be helpful for people who do not have a good response to a prescription antidepressant. Giving SAMe as an injection or as a shot also seems to improve depression as effectively as some prescription medications used for depression. But lower doses of SAMe (100-200 mg) might not improve depression scores in people with mild to moderate depression when given as an injection or a shot. SAMe should not be taken in combination with a prescription antidepressant without the monitoring of a health professional.
- Osteoarthritis. Taking SAMe by mouth seems to work about as well as aspirin and similar medications for reducing symptoms of osteoarthritis. 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.
Possibly Effective for...
- Symptoms of AIDS-related nerve problems. Taking SAMe intravenously (by IV) seems to improve some symptoms caused by AIDS related to nerve problems.
- Cirrhosis. Most early research suggests that taking SAMe by mouth or intravenously (by IV) improves liver function in people with chronic liver disease or cirrhosis. But some research suggests that giving SAMe by IV after surgery does not reduce the risk of mild liver dysfunction in patients with cirrhosis who undergo liver resection.
- Fibromyalgia. Some research suggests that taking SAMe by mouth improves symptoms of fibromyalgia. However, evidence on the use of SAMe intravenously for fibromyalgia is inconsistent. Some research suggests it may reduce symptoms such as pain and number of tender points, while other research shows that it does not.
- Condition in which the flow of bile from the liver is slow or blocked (Intrahepatic cholestasis). Taking SAMe by mouth or intravenously (by IV) short-term seems to help reduce symptoms of intrahepatic cholestasis. This condition can be caused by acute or chronic liver diseases, as well as pregnancy. SAMe seems to reduce symptoms such as itching, tiredness, and markers of liver damage. In women with intrahepatic cholestasis of pregnancy, SAMe also seems to reduce preterm births better than prescription medications called beta-mimetics, which are given to suppress preterm labor. But SAMe does not seem reduce symptoms of intrahepatic cholestasis better than a prescription medication called ursodeoxycholic acid.
- Sexual dysfunction. Research suggests that taking SAMe by mouth in addition to antidepressants improves sexual dysfunction in men with depression.
Insufficient Evidence to Rate Effectiveness for...
- Alcohol-related liver disease. Evidence on the effect of SAMe in alcohol-related liver disease is inconsistent. Some early research shows that taking SAMe by mouth or intravenously (by IV) reduces some symptoms associated with liver disease, such as jaundice and ankle swelling. However, it does not affect some liver function tests or reduce death or complications in people with alcohol-related liver disease.
- Attention deficit-hyperactivity disorder (ADHD). Research on the effects of SAMe in people with ADHD is not clear. Early research suggests that SAMe might reduce ADHD symptoms in adults. However, other research suggests it does not improve symptoms.
- Abdominal pain for which there is no obvious cause (Functional abdominal pain). Early research suggests that taking a daily multivitamin and SAMe by mouth might reduce stomach pain in children with functional abdominal pain. But it does not appear to completely eliminate pain.
- Gilbert syndrome. People with Gilbert syndrome have a lower amount of the protein that normally helps break down a chemical called bilirubin. As a result, too much bilirubin to build up in the body. This can lead to jaundice or other symptoms. Early research suggests that taking SAMe by mouth or intravenously (by IV) might help break down bilirubin in people with Gilbert syndrome.
- Hepatitis. Early research suggests that taking SAMe by mouth or intravenously improves liver function in people with hepatitis. But most of these studies were small and of low quality.
- Schizophrenia. Early research suggests that SAMe might reduce aggressive behavior in people with schizophrenia.
- Blood infection (Sepsis). Early research shows that taking SAMe along with the drug sulodexide reduces the amount of time needed to recover from a septic infection.
- Quitting smoking. Early research suggests that taking SAMe (Nature Made, Pharmavite LLC, Gnosis, Italy) by mouth does not help people quit smoking.
- 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.
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 when taken by mouth, given intravenously (by IV), or when injected as a shot, appropriately. It can sometimes cause gas, vomiting, diarrhea, constipation, dry mouth, headache, mild insomnia, anorexia, sweating, dizziness, and nervousness, especially at higher doses. It can also make some people with depression feel anxious.
Special Precautions & Warnings:Pregnancy: SAMe is POSSIBLY SAFE when given intravenously (by IV) in the short-term during the third trimester of pregnancy. An 800 mg dose of SAMe has been used intravenously for 14-20 days without any adverse effects. There is not enough reliable information about the safety of taking higher doses of SAMe for longer periods of time or during the earlier trimesters of pregnancy. Stay on the safe side and avoid use.
Breast-feeding: There is not enough reliable information about the safety of taking SAMe if you are pregnant or breast feeding. Stay on the safe side and avoid use.
Children: SAMe is POSSIBLY SAFE when taken by mouth or used intravenously (by IV) in children in the short-term.
Inherited disorder called Lesch-Nyhan syndrome: SAMe might make symptoms of Lesch-Nyhan syndrome worse.
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.
Dextromethorphan (Robitussin DM, and others)Interaction Rating: Major Do not take this combination.
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)Interaction Rating: Major Do not take this combination.
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.
Medications for depression (MAOIs)Interaction Rating: Major Do not take this combination.
SAMe increases a chemical in the brain 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.
LevodopaInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.
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.
Meperidine (Demerol)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
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.
Pentazocine (Talwin)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
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)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
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.
The following doses have been studied in scientific research:
- For depression: Up to 1600 mg of SAMe daily in two divided doses for up to 8 weeks has been used alone or together with antidepressant medications. A combination product (DDM Metile, Omeopiacenza, Piacenza, Italy) containing 250 mg of SAMe taken twice daily for 12 months has been used.
- For osteoarthritis: 600-1200 mg of SAMe daily in up to three divided doses for up to 84 days has been used.
- For cirrhosis: 600 mg of SAMe daily for one month has been used. A combination 30 mg of SAMe plus 100 mcg of vitamin B12 six times daily for 30 days has been used.
- For fibromyalgia: 800 mg per of SAMe daily in two divided doses for 6 weeks has been used.
- For conditions in which bile flow from the liver is slow or blocked (Intrahepatic cholestasis): 500 mg of SAMe taken twice daily until delivery or 1600 mg taken daily in two divided doses for 2 weeks has been used.
- For sexual dysfunction: 400 mg of SAMe taken twice daily for 2 weeks, then increased to 800 mg twice daily for another 6 weeks, has been used.
- For depression: 400-800 mg of SAMe has been used intravenously (by IV) for 2-4 weeks. 45-400 mg of SAMe has been injected as a shot daily for 1-4 weeks, with or without antidepressant drugs. 200 mg of SAMe has been injected as a shot daily along with 400 mg taken by mouth in two divided doses for 6 weeks.
- For osteoarthritis: 400 mg of SAMe has been given by IV daily for 5 days, followed by 600 mg of SAMe taken by mouth in three divided doses for 23 days. 60 mg of SAMe injected as a shot for 7 days has also been used.
- For cirrhosis: 800 mg of SAMe has been used by IV once daily for 2 weeks, or 250 mg twice daily for 30 days. 1000 mg of a specific product (Transmetil, Abbott SPA) given by IV has been used daily for 7 days. 100 mg of SAMe given as a shot once daily for 30 days has also been used.
- For fibromyalgia: 400 mg of SAMe given by IV daily for 15 days has been used. 200 mg of SAMe given as a shot daily for 21 days has also been used.
Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, and Insufficient Evidence to Rate (detailed description of each of the ratings).
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Health Solutions From Our Sponsors
Adachi Y, Nanno T, Kanbe A, and et al. The effects of S-adenosylmethionine on intrahepatic cholestasis. Jpn Arch Intern Med 1986;33(6):185-192.
Agency for Healthcare Research and Quality. S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease. Evidence Report/Technology Assessment: Number 64 2002;
Agnoli, A., Andreoli, V., Casacchia, M., and Cerbo, R. Effect of s-adenosyl-l-methionine (SAMe) upon depressive symptoms. J Psychiatr.Res 1976;13(1):43-54. View abstract.
Agricola R, Dalla Verde G, Urani R, and et al. S-adenosyl-L-methionine in the treatment of major depression complicating chronic alcoholism. Curr Ther Res 1994;55(1):83-92.
Altomare E, Vendemiale G Marchesini G Le Grazie C Di Padova C. Increased bioavailability of sulfurated compounds after s-adeno- sylmethionine (SAMe) administration to alcoholics. Biomedical and social aspects of alcohol and alcoholism. 1988;353-356.
Andreoli V, Campedelli A, and Maffei F. La S-adenosil-L-metionina (SAMe) in geropsichiatria: uno studio clinico controllato "in aperto" nelle sindromi depressive dell'eta senile. Giornale di Gerontologia 1977;25:172-180.
Anstee, Q. M. and Day, C. P. S-adenosylmethionine (SAMe) therapy in liver disease: a review of current evidence and clinical utility. J.Hepatol. 2012;57(5):1097-1109. View abstract.
Barberi A and Pusateri C. Sugli effetti clinici della S-adenosil-L-metionina (SAMe) nelle sindromi depressive. Minerva Psichiatrica 1978;19:235-243.
Bell KM, Potkin SG, Carreon L, and et al. Oral S-adenosylmethionine in the treatment of depression: a double blind, randomized comparison with desipramine. Study Report BioResearch File 1990;
Belmont AD, Henkel RD, and Ancira FU. [Parenteral SAMe as compared to a placebo in the treatment of alcoholic liver disease]. An Med Interna 1996;13(1):9-15.
Bombardieri G, Milani A, Bernardi L, and et al. Effects of S-adenosyl-L-methionine (SAMe) in the treatment of Gilbert's syndrome. Curr Ther Res 1985;37(3):580-585.
Bonfirraro G, Chieffi O, Quinti R, and et al. S-adenosyl-L-methionine (SAMe)-induced amelioration of intrahepatic cholestasis of pregnancy. Results of an open study. Drug Invest 1990;2(2):125-128.
Bortolini M, Catalino F, Scarponi S, and et al. Efficacy and safety of intravenous (IV) S-adenosylmethionine (SAMe) in the management of intrahepatic cholestatis of pregnancy (ICP) [abstract]. Hepatology 1991;14:250A.
Bottiglieri, T. and Hyland, K. S-adenosylmethionine levels in psychiatric and neurological disorders: a review. Acta Neurol Scand Suppl 1994;154:19-26. View abstract.
Bottiglieri, T., Godfrey, P., Flynn, T., Carney, M. W., Toone, B. K., and Reynolds, E. H. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 1990;53(12):1096-1098. View abstract.
Bradley, J., Flusser, D., Brandt, K., and et al. S-adenosyl methionine (SAMe) in the treatment of osteoarthritis (OA) of the knee. Arthritis Rheum 1991;34(suppl 9):S86.
Bresci, G. and Marchioro, M. Effetti della SAMe sugli indici di funzionalità epatica in corso di epatopatia cronica. Confronto con placebo [Effects of SAMe on liver function tests in patients with chronic liver disease. A comparison with placebo]. Gazz Med Ital 1982;141(10):557-562.
Burrows, R. F., Clavisi, O., and Burrows, E. Interventions for treating cholestasis in pregnancy (Cochrane Review). Cochrane Database.Syst Rev 2001;4:CD000493. View abstract.
Cacciatore L, Varriale A, Cozzolino G, and et al. S-adenosylmethionine (SAMe) in the treatment of pruritus in chronic liver disease. Acta Therapeutica 1989;15:363-371.
Calandra, C., Roxas, M., and Rapisarda, V. [Antidepressant action of SAM in comparison to chlorimipramine. Hypotheses to interpret the mechanism of action]. Minerva Psichiatr. 1979;20(2):147-152. View abstract.
Cantoni, C. J. The Nature of the Active Methyl Donor Formed Enzymatically from L-Methionine and Adenosinetriphosphate. J Am Chem Soc 1952;74(11):2942-3.
Capretto C, Cremona C, and Canaparo L. A double-blind controlled study of S-adenosylmethionine (SAMe) v. ibuprofen in gonarthrosis, coxarthrosis and spondylarthrosis. Clin Trials J 1985;22(1):15-24.
Carney, M. W., Edeh, J., Bottiglieri, T., Reynolds, E. M., and Toone, B. K. Affective illness and S-adenosyl methionine: a preliminary report. Clin Neuropharmacol. 1986;9(4):379-385. View abstract.
Carney, M. W., Martin, R., Bottiglieri, T., Reynolds, E. H., Nissenbaum, H., Toone, B. K., and Sheffield, B. N. Switch mechanism in affective illness and S-adenosylmethionine. Lancet 4-9-1983;1(8328):820-821. View abstract.
Caroli A. Studio in doppio cieco SAMe (capsule) - Aspirina nell'osteoartrosi. G Clin Med 1980;61(11):844-857.
Carpenter, D. J. St. John's wort and S-adenosyl methionine as "natural" alternatives to conventional antidepressants in the era of the suicidality boxed warning: what is the evidence for clinically relevant benefit? Altern.Med.Rev. 2011;16(1):17-39. View abstract.
Carrieri PB, Indaco A, Gentile S, and et al. S-adenosylmethionine treatment of depressioin in patients with Parkinson's disease: a double-blind, crossover study versus placebo. Curr Ther Res 1990;48(1):154-160.
Caruso I, Fumagalli M, Boccassini L, and et al. Treatment of depression in rheumatoid arthritic patients. A comparison of S-adenosylmethionine (Samyr*) and placebo in a double-blind study. Clin Trials J 1987;24(4):305-310.
Caruso, I., Fumagalli, M., Boccassini, L., Puttini, P. S., Ciniselli, G., and Cavallari, G. Antidepressant activity of S-adenosylmethionine. Lancet 4-21-1984;1(8382):904. View abstract.
Catalino F, Scarponi S, Cesa F, and et al. Efficacy and safety of intravenous S-adenosyl-L-methionine therapy in the management of intrahepatic cholestasis of pregnancy. Drug Invest 1992;4(Suppl 4):78-82.
Cergnul I, Jones K, Ernst D, and et al. S-adenosylmethionine (SAM-e) in the treatment of depressive disorders in HIV-positive individuals: interim results [poster]. Poster presentation at the13th National HIV/AIDS update conference 2001;
Cerutti PG, Savoini G, D'avola G, and et al. Evaluation of the efficacy of s-adenosylmethionine in the treatment of depressive disorders: a controlled clinical trial against minaprine. Basi Razionali della Terapia 1989;19(10):591-595.
Cerutti R, Sichel MP, Perin M, and et al. Psychological distress during puerperium: a novel therapeutic approach using S-adenosylmethionine. Curr Ther Res 1993;53(6):707-716.
Chinchilla, M. A., Vega Pinero, M., Cebollada Gracia, A., and et al. Latencia antidepresiva y S-Adenosil-Metionina [Antidepressive latency and S-adenosylmethionine]. Anales de Psiquiatria 1996;12(2):67-71.
Chitiva, H., Audivert, F., and Alvarez, C. Suicide attempt by self-burning associated with ingestion of S-adenosylmethionine: a review of the literature and case report. J.Nerv.Ment.Dis. 2012;200(1):99-101. View abstract.
Cibin M, Gentile N, Ferri M, and et al. S-adenosylmethionine (SAMe) is effective in reducing ethanol abuse in an outpatient program for alcoholics. In: Kuriyama K, Takada A, and Ishii H. Biomedical and social aspects of alcohol and alcoholism. Kyoto, Japan: Elsevier Science Publishers BV (Biomedical Division);1988.
Coltorti, M., Bortolini, M., and Di Padova, C. A review of the studies on the clinical use of S-adenosylmethionine (SAMe) for the symptomatic treatment of intrahepatic cholestasis. Methods Find.Exp Clin Pharmacol 1990;12(1):69-78. View abstract.
Corrales F, Pajares M, Pliego M, and et al. Effect of S-adenosylmethionine treatment on methionine intolerance in alcoholic cirrhosis [abstract]. J Hepatol 1991;13(Suppl 2):S111.
Criconia AM, Araquistain JM, Daffina N, and et al. Results of treatment with S-adenosyl-L-methionine in patients with major depression and internal illnesses. Curr Ther Res 1994;55(6):666-674.
Cucinotta, D., Mancini, M., Ceccato, S., and Castino, E. [Controlled clinical study of SAMe (S-adenosylmethionine) administered orally in degenerative osteoarticular pathology]. G.Clin Med 1980;61(7):553-566. View abstract.
De Leo D. S-adenosyl-L-methionine (SAMe) in clinical practice: preliminary report on 75 minor depressives. Curr Ther Res 1985;37(4):658-661.
De Leo D. S-adenosylmethionine as an antidepressant: a double-blind trial versus placebo. Curr Ther Res 1987;41(6):865-870.
De Vanna M and Rigamonti R. Oral S-adenosyl-L-methionine in depression. Curr Ther Res 1992;52(3):478-485.
De, Silva, V, El-Metwally, A., Ernst, E., Lewith, G., and Macfarlane, G. J. Evidence for the efficacy of complementary and alternative medicines in the management of fibromyalgia: a systematic review. Rheumatology.(Oxford) 2010;49(6):1063-1068. View abstract.
Del Vecchio M, Iorio G, Cocorullo M, and et al. Has SAMe (Ado-Met) an antidepressant effect? A preliminary trial versus chlorimipramine. Rivista Sperimentale Freniatria 1978;102:344-358.
Delle Chiaie R and Boissard G. Meta-analysis of 2 European multicenter controlled trials with ademetionine (SAMe) in major depression [abstract]. Biol Psychiatry 1997;42:245S.
Delle Chiaie R and Pancheri P. [Combined analysis of two controlled multicentric, double blind studies to assess efficacy and safety of Sulfo-Adenosyl-Methionine (SAMe) vs. placebo (MC1) and SAMe vs. clomipramine (MC2) in the treatment of major depression]. J Ital Psicopatol 1999;5(1):1-16.
Delle Chiaie R, Panceri P, and Scapicchio P. MC3: multicentre, controlled efficacy and safety trial of oral S-adenosyl-methionine (SAMe) vs. oral imipramine in the treatment of depression. Int J Neuropsychopharmacol 2000;3(Suppl 1):S230.
Di Benedetto P, Iona LG, and Zidarich V. Clinical evaluation of S-adenosyl-L-methionine versus transcutaneous electrical nerve stimulation in primary fibromyalgia. Curr Ther Res 1993;53(2):222-229.
Di Palma, D., Fiore, M., Majoli, M., and et al. Prime acquisizioni sul trattamento delle epatiti acute con SAMe [First acquirements on the treatment of the acute hepatitis with SAMe]. G Mal Infett Parassit 1978;30(8):651-662.
Di Rocco, A., Rogers, J. D., Brown, R., Werner, P., and Bottiglieri, T. S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial. Mov Disord 2000;15(6):1225-1229. View abstract.
Echols, J. C., Naidoo, U., and Salzman, C. SAMe (S-adenosylmethionine). Harv.Rev.Psychiatry 2000;8(2):84-90. View abstract.
Everson, G. T., Ahnen, D., Harper, P. C., and Krawitt, E. L. Benign recurrent intrahepatic cholestasis: treatment with S- adenosylmethionine. Gastroenterology 1989;96(5 Pt 1):1354-1357. View abstract.
Fava, M., Rosenbaum, J. F., Birnbaum, R., Kelly, K., Otto, M. W., and MacLaughlin, R. The thyrotropin response to thyrotropin-releasing hormone as a predictor of response to treatment in depressed outpatients. Acta Psychiatr.Scand 1992;86(1):42-45. View abstract.
Fava, M., Rosenbaum, J. F., MacLaughlin, R., Falk, W. E., Pollack, M. H., Cohen, L. S., Jones, L., and Pill, L. Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant. J Psychiatr.Res 1990;24(2):177-184. View abstract.
Fazio, C., Andreoli, V., Agnoli, A., Casacchia, M., and Cerbo, R. [Therapeutic effects and mechanism of action of S-adenosyl-L-methionine (SAM) in depressive syndromes]. Minerva Med 4-30-1973;64(29):1515-1529. View abstract.
Fetrow, C. W. and Avila, J. R. Efficacy of the dietary supplement S-adenosyl-L-methionine. Ann Pharmacother. 2001;35(11):1414-1425. View abstract.
Freeman, M. P., Mischoulon, D., Tedeschini, E., Goodness, T., Cohen, L. S., Fava, M., and Papakostas, G. I. 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;71(6):682-688. View abstract.
Frezza M and Terpin M. The use of S-adenosyl-L-methionine in the treatment of cholestatic disorders: a meta-analysis of clinical trials. Drug Invest 1992;4(Suppl. 4):101-108.
Frezza M, Cammareri G, Di Padova C, and et al. Beneficial effects of S-adenosylmethionine in pregnant women with cholestasis: results of a multicenter controlled clinical trial [abstract]. J Hepatol 1987;5 suppl 1:S27.
Frezza M, Di Padova C, and Italian Study Group for SAMe. Multicenter placebo controlled clinical trial of intravenous and oral S-adenosyl-L-methionine (SAMe) in cholestatic patients with liver disease [abstract]. Hepatology 1987;7(5):1105.
Frezza, M., Pozzato, G., Chiesa, L., Stramentinoli, G., and Di Padova, C. Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration. Hepatology 1984;4(2):274-278. View abstract.
Frezza, M., Tritapepe, R., Pozzato, G., and Di Padova, C. Prevention of S-adenosylmethionine of estrogen-induced hepatobiliary toxicity in susceptible women. Am J Gastroenterol 1988;83(10):1098-1102. View abstract.
Furujo, M., Kinoshita, M., Nagao, M., and Kubo, T. S-adenosylmethionine treatment in methionine adenosyltransferase deficiency, a case report. Mol.Genet.Metab 2012;105(3):516-518. View abstract.
Gaster B. S-adenosylmethionine (SAMe) for treatment of depression. Alternative Medicine Alert 1999;12:133-135.
Gerards, M., Sluiter, W., van den Bosch, B. J., de Wit, L. E., Calis, C. M., Frentzen, M., Akbari, H., Schoonderwoerd, K., Scholte, H. R., Jongbloed, R. J., Hendrickx, A. T., de Coo, I. F., and Smeets, H. J. Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome. J.Med.Genet. 2010;47(8):507-512. View abstract.
Giulidori, P., Cortellaro, M., Moreo, G., and Stramentinoli, G. Pharmacokinetics of S-adenosyl-L-methionine in healthy volunteers. Eur J Clin Pharmacol 1984;27(1):119-121. View abstract.
Glick, N. Dramatic reduction in self-injury in Lesch-Nyhan disease following S-adenosylmethionine administration. J.Inherit.Metab Dis. 2006;29(5):687. View abstract.
Hanje, A. J., Fortune, B., Song, M., Hill, D., and McClain, C. The use of selected nutrition supplements and complementary and alternative medicine in liver disease. Nutr.Clin.Pract. 2006;21(3):255-272. View abstract.
Hardy, M. L., Coulter, I., Morton, S. C., Favreau, J., Venuturupalli, S., Chiappelli, F., Rossi, F., Orshansky, G., Jungvig, L. K., Roth, E. A., Suttorp, M. J., and Shekelle, P. S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease. Evid.Rep.Technol.Assess.(Summ.) 2003;(64):1-3. View abstract.
Ianniello A, Ostuni PA, Sfriso P, and et al. S-adenosyl-L-methionine in Sjögren's syndrome and fibromyalgia. Curr Ther Res 1994;55(6):699-706.
Jorge, A. D. Accion terapeutica de la SAMe en hepatitis aguda [Therapeutic action of the S-adenosyl-L-methionine in acute hepatitis]. Prensa Med Argent 1985;72(11):373-379.
Jorm, A. F., Allen, N. B., O'Donnell, C. P., Parslow, R. A., Purcell, R., and Morgan, A. J. Effectiveness of complementary and self-help treatments for depression in children and adolescents. Med J Aust 10-2-2006;185(7):368-372. View abstract.
Kaye, G. L., Blake, J. C., and Burroughs, A. K. Metabolism of exogenous S-adenosyl-L-methionine in patients with liver disease. Drugs 1990;40 Suppl 3:124-128. View abstract.
Kharbanda, K. K. Methionine metabolic pathway in alcoholic liver injury. Curr.Opin.Clin.Nutr.Metab Care 2013;16(1):89-95. View abstract.
Kharbanda, K. K., Bardag-Gorce, F., Barve, S., Molina, P. E., and Osna, N. A. Impact of altered methylation in cytokine signaling and proteasome function in alcohol and viral-mediated diseases. Alcohol Clin.Exp.Res. 2013;37(1):1-7. View abstract.
Konig, H. and Saal, J. [Quantitatively evaluated magnetic resonance tomography as a therapeutic follow-up of the nonsteroidal antirheumatic ademetionin: a pilot study in patients with gonarthrosis]. Rofo 1990;152(2):214-219. View abstract.
Kufferle, B. and Grunberger, J. Early clinical double-blind study with S-adenosyl-L-methionine: a new potential antidepressant. Adv.Biochem.Psychopharmacol. 1982;32:175-180. View abstract.
Labo, G. and Gasbarrini, G. B. [Therapeutic action of S-adenosylmethionine in some chronic hepatopathies]. Minerva Med 5-2-1975;66(33):1563-1570. View abstract.
Lafuenti, G., Plotti, G., Nicolanti, G., and et al. Valutazione del rischio ostetrico in gravide con colestasi intraepatica in terapia con S-adenosyl-L-methionine [Evaluation of the obstetrical risk in pregnant women with intrahepatic cholestasis treated with S-adenosyl-L-methionine]. Recenti Prog Med 1988;79(10):420-423.
Levkovitz, Y., Alpert, J. E., Brintz, C. E., Mischoulon, D., and Papakostas, G. I. Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. Eur.Psychiatry 2012;27(7):518-521. View abstract.
Li, N., Zhang, H. H., Wang, S. H., Zhu, W. M., Ren, J. A., and Li, J. S. S-adenosylmethionine in treatment of cholestasis after total parenteral nutrition: laboratory investigation and clinical application. Hepatobiliary.Pancreat.Dis.Int. 2002;1(1):96-100. View abstract.
Lo Russo, A., Monaco, M., Pani, A., and et al. Efficacy of s-adenosyl-l-methionine in relieving psychologic distress associated with detoxification in opiate users. Curr Ther Res 1994;55(8):905-913.
Lu, S. C. and Mato, J. M. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012;92(4):1515-1542. View abstract.
Mantero, M., Pastorino, P., Carolei, A., and Agnoli, A. [Controlled double-blind study (SAMe-imipramine) in depressive syndromes]. Minerva Med 11-17-1975;66(78):4098-4101. View abstract.
Manzillo G, Piccinino F, Surrenti C, and et al. Multicentre double-blind placebo-controlled study of intravenous and oral S-adenosyl-L-methionine (SAMe) in cholestatic patients with liver disease. Drug Invest 1992;4 (Suppl. 4):90-100.
Marchesini G, Bugianesi E, Bianchi G, and et al. Effect of S-adenosyl-L-methionine administration on plasma levels of sulphur-containing amino acids in patients with liver cirrhosis. Clinical Nutrition 1992;11:303-308.
Marcolongo R, Giordano N, and Colombo B. Double-blind multicentre study of the activity of S-adenosyl-L-methionine in hip and knee osteoarthritis. Curr Ther Res 1985;37(1):82-94.
Mascio G, Guida L, Ferbo U, and et al. Trattamento della steatosi epatica pura o associata ad altre epatopatie. Gazzetta Medica Italiana 1981;140:37-44.
Micali M, Chiti D, and Balestra V. Double-blind controlled clinical trial of SAMe administered orally in chronic liver diseases. Curr Ther Res 1983;33(6):1004-1013.
Miccoli, L., Porro, V., and 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. View abstract.
Mischoulon, D., Alpert, J. E., Arning, E., Bottiglieri, T., Fava, M., and Papakostas, G. I. Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder. J.Clin.Psychiatry 2012;73(6):843-848. View abstract.
Monaco, P. and Quattrocchi, F. [Study of the antidepressive effects of a biological transmethylating agent (S-adenosyl-methione or SAM)]. Rivista di Neurologia 1979;49(6):417-439. View abstract.
Montrone, F., Fumagalli, M., Sarzi, Puttini P., Boccassini, L., Santandrea, S., Volpato, R., Locati, M., and Caruso, I. Double-blind study of S-adenosyl-methionine versus placebo in hip and knee arthrosis. Clin Rheumatol 1985;4(4):484-485 . View abstract.
Nierenberg, A. A., Kansky, C., Brennan, B. P., Shelton, R. C., Perlis, R., and Iosifescu, D. V. Mitochondrial modulators for bipolar disorder: a pathophysiologically informed paradigm for new drug development. Aust.N.Z.J.Psychiatry 2013;47(1):26-42. View abstract.
Papakostas, G. I., Alpert, J. E., and Fava, M. S-adenosyl-methionine in depression: a comprehensive review of the literature. Curr.Psychiatry Rep. 2003;5(6):460-466. View abstract.
Papakostas, G. I., Cassiello, C. F., and Iovieno, N. Folates and S-adenosylmethionine for major depressive disorder. Can.J.Psychiatry 2012;57(7):406-413. View abstract.
Pecoraro, V., Bruno, M., and Giammona, R. L'impiego terapeutico della SAMe (s-adenosil-l-metionina) nella epatite virale acuta [Therapy with SAMe (s-adenosyl-l-methionine) in acute viral hepatitis]. G Mal Infett Parassit 1979;31(6):390-394.
Plasencia AM, Garcia MM, Torres AC, and et al. Total parenteral nutrition plus S-adenosylmethionine in a case of intrahepatic cholestasis. Drug Investigation 1991;3(5):333-335.
Porter, N. S., Jason, L. A., Boulton, A., Bothne, N., and Coleman, B. Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia. J.Altern.Complement Med. 2010;16(3):235-249. View abstract.
Potkin, S. G., Bell, K., Plon, L., and Bunney, W. E., Jr. Rapid antidepressant response with SAMe. A double-blind study. Alabama Journal of Medical Sciences 1988;25(3):313-316. View abstract.
Qin, B., Guo, S., Zhao, Y., Zou, S., Zhang, Q., Wang, Z., Zeng, W., and Zhang, D. A trial of ademetionine in the treatment of intrahepatic biliary stasis viral hepatitis. Zhonghua Gan Zang.Bing.Za Zhi 2000;8(3):158-160. View abstract.
Ribalta, J., Reyes, H., Gonzalez, M. C., Iglesias, J., Arrese, M., Poniachik, J., Molina, C., and Segovia, N. S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo- controlled study with negative results. Hepatology 1991;13(6):1084-1089. View abstract.
Roncaglia N, Locatelli A, Bellini P, and et al. A randomized controlled trial of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of gestational cholestasis. Am J Obstet Gynecol 2000;182(1 pt 2):S167.
Rosenbaum, J. F., Fava, M., Falk, W. E., Pollack, M. H., Cohen, L. S., Cohen, B. M., and Zubenko, G. S. An open-label pilot study of oral S-adenosylmethionine in major depression. An interim report. Ala J Med Sci 1988;25(3):301-306. View abstract.
Rutjes, A. W., Nuesch, E., Reichenbach, S., and Juni, P. S-Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane.Database.Syst.Rev. 2009;(4):CD007321. View abstract.
Salvadorini F, Galeone F, Saba P, and et al. Evaluation of S-adenosyl-L-methionine (SAMe) effectiveness on depression. Current Therapeutic Research 1980;27(6 section 2):908-917.
Santini, D., Vincenzi, B., Massacesi, C., Picardi, A., Gentilucci, U. V., Esposito, V., Liuzzi, G., La Cesa, A., Rocci, L., Marcucci, F., Montesarchio, V., Groeger, A. M., Bonsignori, M., and Tonini, G. S-adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injury. Anticancer Res 2003;23(6D):5173-5179. View abstract.
Sarris, J. Clinical depression: an evidence-based integrative complementary medicine treatment model. Altern.Ther.Health Med. 2011;17(4):26-37. View abstract.
Scaggion, G., Baldan, L., Domanin, S., Sivo, M., Cenci, I., Beggio, R., and Castorina, G. [Antidepressive action of S-adenosylmethionine compared to nomifensine maleate]. Minerva Psichiatr. 1982;23(2):93-97. View abstract.
Scarzella R and Appiotti A. Confronto clinico in doppio cieco della SAMe versus clorimipramina nelle sindromi depressive. Rivista Sperimentale di Freniatria 1978;102:359-365.
Schaller, J. L., Thomas, J., and Bazzan, A. J. SAMe use in children and adolescents. Eur.Child Adolesc.Psychiatry 2004;13(5):332-334. View abstract.
Shippy, R. A., Mendez, D., Jones, K., Cergnul, I., and Karpiak, S. E. S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS. BMC.Psychiatry 11-11-2004;4:38. View abstract.
Silveri, M. M., Parow, A. M., Villafuerte, R. A., Damico, K. E., Goren, J., Stoll, A. L., Cohen, B. M., and Renshaw, P. F. S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects. Biol.Psychiatry 10-15-2003;54(8):833-839. View abstract.
Stramentinoli, G. Pharmacologic aspects of S-adenosylmethionine. Pharmacokinetics and pharmacodynamics. Am J Med 11-20-1987;83(5A):35-42. View abstract.
Trespi A, Vigoni R, Matti C, and et al. TUDCA, UDCA and Ademetionine (Ade) in the treatment of alcohol-induced liver damage [abstract]. J Hepatol 1997;26:128.
Vendemiale, G., Altomare, E., Trizio, T., Le Grazie, C., Di Padova, C., Salerno, M. T., Carrieri, V., and Albano, O. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scand J Gastroenterol 1989;24(4):407-415. View abstract.
Williams, A. L., Girard, C., Jui, D., Sabina, A., and Katz, D. L. S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clin Invest Med 2005;28(3):132-139. View abstract.
Yang, J., He, Y., Du, Y. X., Tang, L. L., Wang, G. J., and Fawcett, J. P. Pharmacokinetic properties of S-adenosylmethionine after oral and intravenous administration of its tosylate disulfate salt: a multiple-dose, open-label, parallel-group study in healthy Chinese volunteers. Clin.Ther. 2009;31(2):311-320. View abstract.
Yousef, I. M., Barnwell, S. G., Tuchweber, B., Weber, A., and Roy, C. C. Effect of complete sulfation of bile acids on bile formation in rats. Hepatology 1987;7(3):535-542. View abstract.
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. View abstract.
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. View abstract.
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(6):661-64. View abstract.
American Dental Association. "ADA Statement on FDA Toothpaste Warning Labels" http://www.ada.org/prof/prac/issues/statements/fluoride.html (Accessed 18 November 2002).
Ancarani E, Biondi B, Bolletta A, et al. Major depression complicating hemodialysis in patients with chronic renal failure: a multicenter, double-blind, controlled clinical trial of S-adenosyl-L-methionine versus placebo. Curr Ther Res 1993;54(6):680-6.
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. View abstract.
Baldessarini RJ. Neuropharmacology of S-adenosyl-L-methionine. Am J Med 1987;83:95-103. View abstract.
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. View abstract.
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. View abstract.
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. View abstract.
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. View abstract.
Binder T., Salaj P., Zima T., Vitek L. [Ursodeoxycholic acid, S-adenosyl-L-methionine and their combinations in the treatment of gestational intrahepatic cholestasis (ICP)]. Ceska Gynekol 2006;71(2):92-98. View abstract.
Binder T., Salaj P., Zima T., Vitek L. Randomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis of pregnancy. J Perinat Med 2006;34(5):383-391. View abstract.
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(3):580-585.
Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52. View abstract.
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. View abstract.
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. View abstract.
Bresci G., Marchioro M. Effetti della SAMe sugli indici di funzionalità epatica in corso di epatopatia cronica. Confronto con placebo [Effects of SAMe on liver function tests in patients with chronic liver disease. A comparison with placebo]. Gazz Med Ital 1982;141(10):557-562.
Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl 1994;154:7-14. View abstract.
Buzzelli G., Moscarella S., Focardi G., Dattolo P., Giusti A., Calviani L., Relli P., Gentilini, P. [Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study]. Minerva Med 1992;83(9):537-540. View abstract.
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.
Carrieri PB, Indaco A, Gentile S, et al. S-adenosylmethionine treatment of depressioin in patients with Parkinson's disease: a double-blind, crossover study versus placebo. Curr Ther Res 1990;48(1):154-60.
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.
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. View abstract.
Ceccato S, Cucinotta D, Carapezzi C, et al. [Double-blind clinical study of the therapeutic effect of SAMe and Ibuprofen in degenerative osteoarticular pathology]. G Clin Med 1980;61(2):148-62. View abstract.
Cerutti PG, Savoini G, D'avola G, et al. Evaluation of the efficacy of s-adenosylmethionine in the treatment of depressive disorders: a controlled clinical trial against minaprine. Basi Razionali della Terapia 1989;19(10):591-95.
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.. View abstract.
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. View abstract.
Choi LJ, Huang JS. A pilot study of S-adenosylmethionine in treatment of functional abdominal pain in children. Altern Ther Health Med 2013;19(5):61-4. View abstract.
Cowley G, Underwood A. Newsweek. July 5, 1999; pp. 46-50.
Czap A. Beware the son of SAMe. Altern Med Rev 1999;4:73. View abstract.
De Silva V, El-Metwally A, Ernst E, et al. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford) 2011;50(5):911-920. View abstract.
De Vanna M, Rigamonti R. Oral S-adenosyl-L-methionine in depression. Curr Ther Res 1992;52:478-85.
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. View abstract.
Di Benedetto P, Iona LG, Zidarich V. Clinical evaluation of S-adenosyl-L-methionine versus transcutaneous electrical nerve stimulation in primary fibromyalgia. Curr Ther Res 1993;53(2):222-229.
di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med 1987;83:60-5. View abstract.
Di Palma D., Fiore M., Majoli M., et al. Prime acquisizioni sul trattamento delle epatiti acute con SAMe [First acquirements on the treatment of the acute hepatitis with SAMe]. G Mal Infett Parassit 1978;30(8):651-662.
Di Pierro F, Settembre R. Preliminary results of a randomized controlled trial carried out with a fixed combination of S-adenosyl-L-methionine and betaine versus amitriptyline in patients with mild depression. Int J Gen Med 2015;8:73-8. View abstract.
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. View abstract.
Dolcetta D, Parmigiani P, Salmaso L, Bernardelle R, Cesari U, Andrighetto G, Baschirotto G, Nyhan WL, Hladnik U. Quantitative evaluation of the clinical effects of S-adenosylmethionine on mood and behavior in Lesch-Nyhan patients. Nucleosides Nucleotides Nucleic Acids 2013;32(4):174-88. View abstract.
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. View abstract.
Dording C. M., Mischoulon D., Shyu I., Alpert J. E., Papakostas G. I. SAMe and sexual functioning. Eur Psychiatry 2012;27(6):451-454. View abstract.
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. View abstract.
FDA. List of orphan designations and approvals. Office of Orphan Products Development. Available at: www.fda.gov/orphan/designat/list.htm.
Feld J. J., Modi A. A., El-Diwany R., Rotman Y., Thomas E., Ahlenstiel G., Titerence R., Koh C., Cherepanov V., Heller T., Ghany M. G., Park Y., Hoofnagle J. H., Liang, T. J. S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. Gastroenterology 2011;140(3):830-839. View abstract.
Filipowicz M., Bernsmeier C., Terracciano L., Duong F. H., Heim M. H. S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse. PLoS One 2010;5(11):e15492. View abstract.
Floreani A., Paternoster D., Melis A., Grella P. V. 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(2):109-113. View abstract.
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. View abstract.
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. View abstract.
Frezza M. [A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]. Ann Ital Med Int 1993;8 Suppl:48S-51S. View abstract.
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. View abstract.
Gaster B. S-adenosylmethionine (SAMe) for treatment of depression. Alternative Medicine Alert, 1999;12:133-5.
Gentile S., Persico M., Orlando C., Le Grazie C., Di Padova C., Coltorti M. Effect of different doses of S-adenosyl-L-methionine (SAMe) on nicotinic acid-induced hyperbilirubinaemia in Gilbert's syndrome. Scand J Clin Lab Invest 1988;48(6):525-529. View abstract.
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. View abstract.
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. View abstract.
Green T, Steingart L, Frisch A, et al. The feasibility and safety of S-adenosyl-L-methionine (SAMe) for the treatment of neuropsychiatric symptoms in 22q11.2 deletion syndrome: a double-blind placebo-controlled trial. J Neural Transm 2012;119(11):1417-23. View abstract.
Green T., Steingart L., Frisch A., Zarchi O., Weizman A., Gothelf D. The feasibility and safety of S-adenosyl-L-methionine (SAMe) for the treatment of neuropsychiatric symptoms in 22q11.2 deletion syndrome: a double-blind placebo-controlled trial. J Neural Transm 2012;119(11):1417-1423. View abstract.
Hardy ML, Coulter I, Morton SC, et al. S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease. Evid Rep Technol Assess (Summ) 2003;(64):1-3. View abstract.
Ideo G. [S-Adenosylmethionine: plasma levels in hepatic cirrhosis and preliminary results of its clinical use in hepatology. Double-blind study]. Minerva Med 1975;66(33):1571-1580. View abstract.
Investigator's Brochure: Ademetionine 1,4-butanedisulfonate. Knoll Pharmaceuticals.
Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522. View abstract.
Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol 1991;20:294-302. View abstract.
Janicak P. G., Lipinski J., Davis J. M., Altman E., Sharma R. P. Parenteral S-adenosyl-methionine (SAMe) in depression: literature review and preliminary data. Psychopharmacol Bull 1989;25(2):238-242. View abstract.
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. View abstract.
Jorge, A. D. Accion terapeutica de la SAMe en hepatitis aguda [Therapeutic action of the S-adenosyl-L-methionine in acute hepatitis]. Prensa Med Argent 1985;72(11):373-379.
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. View abstract.
Kim J, Lee EY, Koh EM, et al. Comparative 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 patients. Clin Ther 2009;31(12):2860-2872. View abstract.
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.
Lafuenti G., Plotti G., Nicolanti G., Gaglione R., Tibollo F. G., Mancuso S. [Evaluation of the obstetrical risk in pregnant women with intrahepatic cholestasis treated with S-adenosyl-L-methionine]. Recenti Prog Med 1988;79(10):420-423. View abstract.
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. View abstract.
Lieber CS, Packer L. S-Adenosylmethionine: molecular, biological, and clinical aspects—an introduction. Am J Clin Nutr 2002;76:1148S-50S.. View abstract.
Lieber CS. S-Adenosyl-L-methionine: its role in the treatment of liver disorders. Am J Clin Nutr 2002;76:1183S-17S.. View abstract.
Lipinski JF, Cohen BM, Frankenburg F, et al. Open trial of S-adenosylmethionine for treatment of depression. Am J Psychiatry 1984;141:448-50. View abstract.
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. View abstract.
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. View abstract.
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. View abstract.
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. View abstract.
Manzillo G, Piccinino F, Surrenti C, et al. Multicentre double-blind placebo-controlled study of intravenous and oral S-adenosyl-L-methionine (SAMe) in cholestatic patients with liver disease. Drug Invest 1992;4 (Suppl 4):90-100.
Marchesini G, Bugianesi E, Bianchi G, et al. Effect of S-adenosyl-L-methionine administration on plasma levels of sulphur-containing amino acids in patients with liver cirrhosis. Clinical Nutrition 1992;11:303-308.
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.. View abstract.
Mascio G, Guida L, Ferbo U, et al. Trattamento della steatosi epatica pura o associata ad altre epatopatie. Gazzetta Medica Italiana 1981;140:37-44.
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. View abstract.
Medici V., Virata M. C., Peerson J. M., Stabler S. P., French S. W., Gregory J. F. III, Albanese A., Bowlus C. L., Devaraj S., Panacek E. A., Richards J. R., Halsted C. H. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial. Alcohol Clin Exp Res 2011;35(11):1960-1965. View abstract.
Micali M, Chiti D, Balestra V. Double-blind controlled clinical trial of SAMe administered orally in chronic liver diseases. Curr Ther Res 1983;33(6):1004-1013.
Miglio F., Stefanini G. F., Corazza G. R., D'Ambro A., Gasbarrini G. [Double-blind studies of the therapeutic action of S-Adenosylmethionine (SAMe) in oral administration, in liver cirrhosis and other chronic hepatitides]. Minerva Med 1975;66(33):1595-1599. View abstract.
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.. View abstract.
Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987;83:81-3. View abstract.
Murphy BL, Babb SM, Ravichandran C, Cohen BM. Oral SAMe in persistent treatment-refractory bipolar depression: a double-blind, randomized clinical trial. J Clin Psychopharmacol 2014;34(3):413-6. View abstract.
Muscettola G, Galzenati M, Balbi A. SAMe versus placebo: a double blind comparison in major depressive disorders. Advances in Biochemical Psychopharmacology 1982;32:151-6. View abstract.
Musso A., Giacchino M., Vietti M., Vaccino P., Cerutti, A. [The use of silymarin and SAMe in the treatment of acute infective hepatitis in childhood]. Minerva Pediatr 1980;32(17):1057-1067. View abstract.
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. View abstract.
Nelson JC. S-adenosyl methionine (SAMe) augmentation in major depressive disorder. (Editorial). Am J Psychiatry 2010;167:889-91. View abstract.
Nicastri P. L., Diaferia A., Tartagni M., Loizzi P., Fanelli M. 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(11):1205-1207. View abstract.
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. View abstract.
Pellegrini P. [S-adenosylmethionine (SAMe) in osteoarthrosis; a double-blind crossover peroral study]. G Clin Med 1980;61(8):616-27. View abstract.
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. View abstract.
Plotkin L. L., Bespalov A. M., Smirnov D. M., Timchenko N. N., Shapovalova IuS, Konradi A. B. [Clinical signs of endothelial disorders in patients with severe sepsis]. Anesteziol Reanimatol 2012;(2):48-51. View abstract.
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. View abstract.
Polli E, Cortellaro M, Parrini L, et al. [Pharmacological and clinical aspects of S-adenosylmethionine (SAMe) in primary degenerative arthropathy (osteoarthrosis)]. Minerva Med 1975;66(83):4443-59. View abstract.
PremesisRx. Pharmacist's Letter / Prescriber's Letter 1999:15(12);151206.
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. View abstract.
Rambaldi A, Gluud C. S-adenosyl-L-methionine for alcoholic liver diseases. Cochrane Database Syst Rev 2006;(2):CD002235. View abstract.
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. View abstract.
Roncaglia N., Locatelli A., Arreghini A., Assi F., Cameroni I., Pezzullo J. C., Ghidini A. A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis. BJOG 2004;111(1):17-21. View abstract.
Rosenbaum J. F., Fava M., Falk W. E., Pollack M. H., Cohen L. S., Cohen B. M., Zubenko G. S. An open-label pilot study of oral S-adenosyl-L-methionine in major depression: interim results. Psychopharmacol Bull 1988;24(1):189-194. View abstract.
Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432-6. View abstract.
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.. View abstract.
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. View abstract.
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.. View abstract.
Shilov V. V., Shikalova I. A., Vasil'ev S. A., Batotsyrenov B. V., Andrianov Alu. [Correction of metabolic disorders during treatment of alcohol-induced liver injuries in patients with acute alcoholic intoxication]. Klin Med (Mosk) 2013;91(2):45-48. View abstract.
Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. View abstract.
Soeken KL, Lee WL, Bausell RB, et al. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract 2002;51:425-30. View abstract.
Sood A, Prasad K, Croghan IT, et al. S-adenosyl-L-methionine (SAMe) for smoking abstinence: a randomized clinical trial. J Altern Complement Med 2012;18(9):854-9. View abstract.
Stramentinoli G, Gualano M, Galli-Kienle M. Intestinal absorption of S-adenosyl-L-methionine. J Pharmacol Exp Ther 1979;209:323-6. View abstract.
Strous R. D., Ritsner M. S., Adler S., Ratner Y., Maayan R., Kotler M., Lachman H., Weizman, A. Improvement of aggressive behavior and quality of life impairment following S-adenosyl-methionine (SAM-e) augmentation in schizophrenia. Eur Neuropsychopharmacol 2009;19(1):14-22. View abstract.
Su ZR, Cui ZL, Ma JL, Li JS, Ge YS, Yu JH, Pan JH, Xu GL, Jia WD. Beneficial effects of S-adenosyl-L-methionine on post-hepatectomy residual liver function: a prospective, randomized, controlled clinical trial. Hepatogastroenterology 2013;60(125):1136-41. View abstract.
Sun Q. F., Ding J. G., Wang X. F., Fu R. Q., Yang J. X., Hong L., Xu X. J., Wang J. R., Wu J. G., Xu D. Z. Efficacy and safety of intravenous stronger neo-minophagen C and S-adenosyl-L-methionine in treatment of pregnant woman with chronic hepatitis B: a pilot study. Med Sci Monit 2010;16(8):R9-14. View abstract.
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. View abstract.
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. View abstract.
Tavoni A., Jeracitano G., Cirigliano G. Evaluation of S-adenosylmethionine in secondary fibromyalgia: a double-blind study. Clin Exp Rheumatol 1998;16(1):106-107. View abstract.
Thomas C. S., Bottiglieri T., Edeh J., Carney M. W., Reynolds E. H., Toone B. K. The influence of S-adenosylmethionine (SAM) on prolactin in depressed patients. Int Clin Psychopharmacol 1987;2(2):97-102. View abstract.
Vahora SA, Malek-Ahmasi P. S-adenosylmethionine in the treatment of depression. Neurosci Biobehav Rev 1988;12:139-41. View abstract.
Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83:78-80. View abstract.
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. View abstract.
Werneke U, Turner T, Priebe S. Complementary medicines in psychiatry: review of effectiveness and safety. Br J Psychiatry 2006;188:109-21. View abstract.
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.
Zhu SS, Dong Y, Gan Y, et al. [Efficacy and safety of ademetionine for treatment of drug-induced liver disease in children]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2010;24(2):136-138. View abstract.