S-adenosyl methionine (SAM-e) - Drugs & Vitamins - Drug Library

Scientific Name: S-adenosyl methionine (SAM-e)
Other Names: Ademetionine, AldoMet, S-adenosyl-L-methionine, SAM, Sammy

Who is this for?

Uses

All proteins, including body tissues, are made from 20 different amino acids. Humans can produce only about half of the amino acids that are needed by various functions within the body. The others, called essential amino acids, come from food or supplements. One of the essential amino acids is methionine, which breaks down in the liver to produce SAM-e.

Neurotransmitters are chemicals that carry messages from nerve cells to other cells. Low levels of the neurotransmitters, dopamine, norepinephrine, and serotonin are associated with depression. SAM-e is known to raise levels of dopamine and norepinephrine in the brain, and it may also accelerate the production, uptake, and re-release of serotonin. Although possible additional antidepressant actions of SAM-e have not been confirmed, results of some studies suggest that SAM-e may increase the sensitivity of receptors that react to these neurotransmitters or improve the ability of neurotransmitters to attach to active receptors. All of these effects are thought to help relieve depression.

SAM-e may also be useful in treating other conditions of the brain and spinal cord, which are known as the central nervous system (CNS). It has been studied for treating dementia—a progressive failure in thought processes caused by brain damage or disease. Alzheimer’s disease is a leading cause of dementia. Frequently, dementia is associated with low levels of SAM-e in the brain and spinal cord and the fluid surrounding them. SAM-e deficiencies have also been identified in individuals who have nerve damage from HIV/AIDS, multiple sclerosis, or spinal cord degeneration. Recent study results show that SAM-e may help to relieve the symptoms of adult attention deficit hyperactivity disorder (ADHD). Additionally, it may relieve symptoms of fibromyalgia, a condition that causes generalized pain in the muscles and joints. SAM-e is being studied for treating all these CNS conditions, but more research is needed to verify its effectiveness for them.

SAM-e is also used widely to treat arthritis. It accumulates in synovial fluid, the thick gel that lubricates and cushions the joints. Chemicals resulting from the body's breakdown of SAM-e are known to relieve pain and fight inflammation, which is one of the body's reactions to irritation, injury, or infection. Inflammation involves pain, redness, and swelling in the area of the damage and it can occur within body structures, such as joints, as well as on the surface of the skin. Additionally, SAM-e may not only prevent the erosion of cartilage by blocking destructive enzymes, it may even stimulate new cartilage to grow.

Individuals with liver conditions—including cirrhosis—often have low levels of methionine in their blood. Furthermore, the ability to convert methionine into SAM-e declines in individuals with liver diseases because the damaged liver cannot produce adequate amounts of the enzymes needed to break down methionine. As a result, the levels of antioxidants that also depend on SAM-e decrease. Antioxidants are thought to protect body cells from damage caused by a chemical process called oxidation. Oxidation produces oxygen free radicals, natural chemicals that may suppress immune function and cause tissue damage.

Glutathione, one of the antioxidants derived from SAM-e, inactivates potentially toxic chemicals such as alcohol, thereby helping to protect the liver from injury. In animal studies, the lack of SAM-e hampered liver cell growth and repair. SAM-e may also help to relieve a condition known as intrahepatic cholestasis, which may be associated with pregnancy, some forms of hepatitis, and other short-term or long-term liver diseases. Intrahepatic cholestasis involves the inability to release bile normally from the liver. Bile builds up and results in symptoms such as intense itching and a yellow-colored skin. In at least two small studies, women who were given SAM-e to control intrahepatic cholestasis in the last third of their pregnancies achieved relief from symptoms while showing no apparent side effects.

SAM-e has been studied for use in a number of other conditions that may be related to methionine or SAM-e deficiencies. For example, many people living with AIDS have low levels of both methionine and SAM-e. Supplemental SAM-e may delay or prevent the spinal cord deterioration (myelopathy) that often accompanies infection with HIV. In addition, SAM-e may help to relieve the depression associated with AIDS. Other studies have found that methionine/SAM-e deficiency during pregnancy may be a factor in abnormal formation of the CNS in developing infants. The resulting “neural tube defects” may lead to extremely serious birth defects such as spina bifida (incomplete closure of the spinal column) or anencephaly (the absence of brain parts). SAM-e supplementation may help to reverse poisoning from. Separate studies in animals show that SAM-e may be an antidote for chronic exposure to low doses of arsenic, lead poisoning, and potentially fatal liver damage that may follow overdoses of acetaminophen (Tylenol). All these possible uses of SAM-e appear promising, but they need further study before SAM-e can be recommended for any of them.

When should I be careful taking it?

Because some study evidence suggests that SAM-e may worsen the symptoms of Parkinson’s disease; individuals who have Parkinson’s disease should not take supplemental SAM-e.

Some individuals with schizophrenia or bipolar disorder have been found to have high levels of SAM-e in their brains. Cases of mania (extreme happiness, excitability, and hyperactivity) have been attributed to the use of supplemental SAM-e by individuals who have bipolar disorder or major depression. Therefore, individuals who have these conditions are advised to take supplemental SAM-e only when its use is supervised by a healthcare professional.

Precautions

Although SAM-e has been studied in pregnant women, its exact effects on a developing fetus are not well known. Therefore, SAM-e supplementation is not recommended during pregnancy.

Not enough is known about how SAM-e might affect an infant to recommend its use while breast-feeding. Small children should also avoid taking SAM-e because its possible long-term effects on growth are not known.

What side effects should I watch for?

Major Side Effects

Serotonin syndrome, a rare but potentially dangerous oversupply of serotonin in the body, may be caused by SAM-e. Uncontrolled serotonin syndrome may result in coma, seizures, and death. Symptoms of serotonin syndrome include:

Confusion
Excitement
Fever
Hallucinations
Inability to coordinate muscles
Restlessness
Shakiness
Vomiting

Less Severe Side Effects

Generally, most side effects associated with taking SAM-e have been mild and temporary. They include:

Anxiety
Constipation
Diarrhea
Dizziness
Dry mouth
Frequent urination
Headache
Insomnia
Nausea
Sweating
Thirst

Injectable SAM-e may be associated with the same side effects as oral SAM-e and it may also cause reactions such as itching or redness at the places where it is injected.

What interactions should I watch for?

Prescription Drugs

If SAM-e is taken with prescription antidepressants that belong to the classes known as selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs), serotonin levels may become excessive. Serotonin syndrome is possible.

SSRIs include fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)
TCAs include amitriptyline, amoxapine, doxepin, and nortriptyline

The risk of side effects from a third type of prescription antidepressants known as monoamine oxidase inhibitors (MAOIs) may be increased if SAM-e is taken at the same time. MAOI therapy should be stopped a minimum of 2 weeks before SAM-e starts. MAOIs include Marplan, Nardil, and tranylcypromine (Parnate). Potential side effects may be:

Aggressive behavior
Coma
Confusion
High blood pressure
High body temperature

Selegiline (Eldepryl) and rasagiline (Azilect), drugs which are related to the MAOI antidepressants and which are used to treat Parkinson's disease, also should not be taken with supplemental SAM-e.

Certain other drugs, such as meperidine and tramadol (Ultram) that are usually given to reduce pain may also raise serotonin levels in the body. If one of these pain-fighting drugs is used at the same time as supplemental SAM-e, the risk of serotonin syndrome may increase.

Non-prescription Drugs

Dextromethorphan (DM) is an anti-coughing ingredient in many non-prescription cough and cold products such as Nyquil and Robitussin DM. Because it may have an increasing effect on serotonin levels, taking dextromethorphan with supplemental SAM-e may result in a higher risk of side effects.

Herbal Products

Potentially, if SAM-e is taken with St John's wort, which also may increase serotonin levels, the risk of serotonin syndrome may also increase.

Some interactions between herbal products and medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how SAM-e interacts with drugs, other herbals, and foods and the severity of those interactions, please use our Drug Interactions Checker to check for possible interactions.

Should I take it?

SAM-e is a chemical that is produced in the body from the metabolism (break down) of methionine, one of the essential amino acids. Amino acids are used by the body primarily to make proteins. Essential amino acids are necessary for body functions, but the body cannot make them—they must be obtained from the diet in foods such as dairy products, fish, meat, and whole grains. Once methionine has been absorbed, enzymes change it into SAM-e, which is found in all cells of the body. In turn, SAM-e breaks down into several chemicals that are involved in a number of basic processes. Some of them maintain the stability and flexibility of cell walls. Others are necessary for the production of essential body components such as hormones and neurotransmitters. Chemicals from SAM-e assist with the processing of dietary fats in the liver and they also act as anti-inflammatory, antioxidant, and pain-controlling agents.

Much of the research on SAM-e has been done in Europe, particularly in Italy, where SAM-e was discovered in the 1950s. Approved as a prescription drug in Italy since 1976 and subsequently in other European countries, SAM-e was not introduced in the United States until the late 1990s. It is a non-prescription oral dietary supplement in this country. Although an ordinary diet usually supplies more than enough methionine to produce adequate amounts of SAM-e, certain groups of individuals, including strict vegetarians and individuals whose immune function has been weakened by chemotherapy or disease, may not produce sufficient amounts. Natural production of SAM-e decreases as individuals age, as well. Commercially available supplemental SAM-e is manufactured from fermented yeasts.

Dosage and Administration

SAM-e is produced within the body by the break down of methionine, which is an amino acid. Known as an essential amino acid because the body needs it to regulate activities such as processing fat in the liver, methionine cannot be made in the body like some of the other amino acids can. It must be taken in the diet or as supplements. Cheese, eggs, fish, meat, milk, nuts, and whole grains are good dietary sources of methionine. Smaller amounts are found in corn, peas, and spinach.

The body’s ability to use SAM-e depends on the availability of other chemicals including folic acid, vitamin B6, and vitamin B12. These three ingredients are often included into a single dietary supplement tablet with SAM-e to make dosing easier and to assure adequate supplies of all four components. Most of the supplemental SAM-e available in the United States comes in enteric-coated tablets because SAM-e is not well absorbed when taken orally. Enteric-coated tablets are designed to resist stomach acid and dissolve in the small intestines, where more of the SAM-e may be absorbed. For the same reason, SAM-e is best taken on an empty stomach, at least one hour before a meal.

Although higher doses have been used in studies, the maximum daily dose of oral supplemental SAM-e is generally considered to be 1,600 mg (1.6 grams). Injectable SAM-e generally is more common in Europe than in the United States, although it may be available to American doctors and clinics. Different doses of SAM-e have been used to treat different conditions. Some common recommendations are:
Condition Oral Dose Range (Daily) Injected Dose Range (Daily)

AIDS myelopathy No recommendation 800 mg

Cirrhosis 1200 mg to 1600 mg No recommendation

Depression 400 mg to 1,600 mg 200 mg to 400 mg

Fibromyalgia 800 mg No recommendation

Intrahepatic Cholestasis 1600 mg 800 mg

Osteoarthritis 600 mg 400 mg

Note: While some individuals have experienced a lessening of depression as soon as 3 days after beginning to take SAM-e, its full effects may take several weeks to develop.

Summary

A substance that results from the breakdown of the dietary amino acid, methionine by the body, SAM-e has shown effectiveness for relieving depression, treating arthritis, and preventing liver damage. It may also be useful in delaying or preventing the deterioration of mental functioning caused by dementia.

Risks

Individuals with Parkinson's disease should avoid using SAM-e because it may worsen symptoms. Small children and women who are pregnant or breast-feeding are advised not to take supplemental SAM-e, and individuals with bipolar disorder or major depression should use SAM-e only with the advice and supervision of a healthcare professional.

Side Effects

A slightly increased risk of serotonin syndrome—a dangerously high level of serotonin in the blood—may be associated with using SAM-e. Its more common and less serious side effects may include:

Anxiety
Constipation
Diarrhea
Dizziness
Headache
Insomnia
Nausea
Sweating

Interactions

SAM-e may increase the chance of developing serotonin syndrome if it is taken with prescription drugs such as SSRI or TCA antidepressants or certain pain-relieving drugs, the non-prescription cough and cold product dextromethorphan, or St. John's wort. The risk of developing side effects including confusion and high blood pressure may be higher if SAM-e is taken within 2 weeks of antidepressants known as MAOIs and related drugs.

Last Revised May 25, 2007

References

Agency for Healthcare Research and Quality. U.S. Department of Health and Human Services. S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease. Evidence Report/Technology Assessment No. 64. (AHRQ 02-E034) October 2002.

Almasio P, Bortolini M, Pagliaro L, Coltorti M. Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis. Drugs. 1990;40(Suppl 3):111-123.

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. Journal of Clinical Psychopharmacology. 2004;24(6):661-664.

Anon: SAME. In: DerMarderosian A, Beutler JA, eds. Facts and Comparisons: The Review of Natural Products. St. Louis, MO. Facts and Comparisons. October 1999.

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. European Neuropsychopharmacology. 2005;15(5):533-543.

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.

Bailey SM, Robinson G, Pinner A, et al. S-adenosylmethionine prevents chronic alcohol-induced mitochondrial dysfunction in the rat liver. American Journal of Physiology and Gastrointestinal Liver Physiology. 2006;291(5):G857-G867.

Baldessarini RJ. Neuropharmacology of S-adenosyl-L-methionine. American Journal of Medicine. 1987;83(5A):95-103.

Bell KM, Plon L, Bunney WE Jr, Potkin SG. S-adenosylmethionine treatment of depression: a controlled clinical trial. American Journal of Psychiatry. 1988;145(9):1110-1114.

Bell KM, Potkin SG, Carreon D, Plon L. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurologica Scandinavia Supplement. 1994;154:15-18.

Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Psychiatry Research. 1992;44(3):257-262.

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. Journal of Perinatal Medicine. 2006;34(5):383-391.

Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside--molecular basis of a pleiotrophic molecule. American Journal of Clinical Nutrition. 2002;76(5):1151S-1157S.

Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs. 1994;48(2):137-152.

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. Journal of Rheumatology. 1994;21(5):905-911.

Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurologica Scandinavia Supplement. 1994;154:7-14.

Brosnan JT, da Silva R, Brosnan ME. Amino acids and the regulation of methyl balance in humans. Current Opinion on Clinical Nutrition and Metabolic Care. 2007;10(1):52-57.

Burrin DG, Stoll B. Emerging aspects of gut sulfur amino acid metabolism. Current Opinion on Clinical Nutrition and Metabolic Care. 2007;10(1):63-68.

Cavallaro RA, Fuso A, D'Anselmi F, Seminara L, Scarpa S. The effect of S-adenosylmethionine on CNS gene expression studied by cDNA microarray analysis. Journal of Alzheimers Disease. 2006;9(4):415-419.

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. Neurology. 1995;45(9):1678-1683.

Charlton CG. Depletion of nigrostriatal and forebrain tyrosine hydroxylase by S-adenosylmethionine: a model that may explain the occurrence of depression in Parkinson's disease. Life Sciences. 1997;61(5):495-502.

Charlton CG, Crowell B Jr. Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacology, Biochemistry and Behavior. 1992 Oct;43(2):423-431.

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(Suppl 3):98-110.

Cohen BM, Satlin A, Zubenko GS. S-adenosyl-L-methionine in the treatment of Alzheimer's disease. Journal of Clinical Psychopharmacology. 1988;8(1):43-47.

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. Behavioral and Neural Biology. 1993;59(3):186-193.

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. American Journal of Clinical Nutrition. 2002;76(5):1172S-1176S.

Del Pilar Cabrales-Romero M, Marquez-Rosado L, Fattel-Fazenda S, et al. S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte cultures by a c-Jun N-terminal kinase activity-independent mechanism. World Journal of Gastroenterology. 2006;12(12):1895-1904.

Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. Psychiatry Research. 1995;56(3):295-297.

Fernandez-Checa J, Colell A, Garcia-Ruiz C. S-Adenosyl-L-methionine and mitochondrial reduced glutathione depletion in alcoholic liver disease. Alcohol 2002;27(3):179-183.

Fetrow CW, Avila JR. Efficacy of the dietary supplement S-adenosyl-L-methionine. Annals of Pharmacotherapy. 2001;35(11):1414-1425.

Frezza M, Centini G, Cammareri G, Le Grazie C, Di Padova C. S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepatogastroenterology. 1990;37(Suppl 2):122-125.

Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, Di Padova C. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology. 1990;99(1):211-215.

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(3):389-416.

Glick N. Dramatic reduction in self-injury in Lesch-Nyhan disease following S-adenosylmethionine administration. Journal of Inherited Metabolic Diseases. 2006;29(5):687.

Glorioso S, Todesco S, Mazzi A, et al. Double-blind, multicentre [sic] study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. International Journal of Clinical Pharmacology Research 1985;5(1):39-49.

Goren JL, Stoll AL, Damico KE, Sarmiento IA, Cohen BM. Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans. Pharmacotherapy. 2004;24(11):1501-1507.

Gruenwald J, Brendler T, Jaenicke C, eds. PDR for Herbal Medicines, 2nd edition. Montvale, NJ: Medical Economics Company, Inc; 2000.

Guidotti A, Ruzicka W, Grayson DR, et al. S-adenosyl methionine and DNA methyltransferase-1 mRNA overexpression in psychosis. Neuroreport. 2007;18(1):57-60.

HealthNotes, Inc. Methionine. 2002. Available at: http://www.mycustompak.com/healthNotes/Supp/Methionine.htm Accessed October 27, 2003.

Innis SM, Davidson AG, Melynk S, James SJ. Choline-related supplements improve abnormal plasma methionine-homocysteine metabolites and glutathione status in children with cystic fibrosis. American Journal of Clinical Nutrition. 2007;85(3):702-708.

Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scandinavian Journal of Rheumatology. 1991;20(4):294-302.

Jellin JM, Gregory P, Batz F, Hitchens K, et al, eds. Pharmacist's Letter/Prescriber's Letter. Natural Medicines Comprehensive Database, 3rd Edition. Stockton CA: Therapeutic Research Facility, 2000.

Jin CJ, Park HK, Cho YM, et al. S-adenosyl-L-methionine increases skeletal muscle mitochondrial DNA density and whole body insulin sensitivity in OLETF rats. Journal of Nutrition. 2007;137(2):339-344.

Jorm AF, Allen NB, O'Donnell CP, Parslow RA, Purcell R, Morgan AJ. Effectiveness of complementary and self-help treatments for depression in children and adolescents. Medical Journal of Australia. 2006;185(7):368-372.

Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. American Journal of Psychiatry. 1990;147(5):591-595.

Lieber CS. S-Adenosyl-L-methionine: its role in the treatment of liver disorders. American Journal of Clinical Nutrition. 2002;76(5):1183S-1187S.

Lieber CS, Packer L. S-Adenosylmethionine: molecular, biological, and clinical aspects-an introduction. American Journal of Clinical Nutrition. 2002;76(5):1148S-1150S.

Lipinski JF, Cohen BM, Frankenburg F, et al. Open trial of S-adenosylmethionine for treatment of depression. American Journal of Psychiatry. 1984;141(3):448-450.

Loehrer FM, Angst CP, Haefeli WE, Jordan PP, Ritz R, Fowler B. Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16(6):727-733.

Loehrer FM, Schwab R, Angst CP, Haefeli WE, Fowler B. Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans. Journal of Pharmacology and Experimental Therapeutics. 1997;22(2):845-850.

Lu SC, Martinez-Chantar ML, Mato JM. Methionine adenosyltransferase and S-adenosylmethionine in alcoholic liver disease. Journal of Gastroenterology and Hepatology. 2006;21(Suppl 3):S61-S64.

Maccagno A, Di Giorgio EE, Caston OL, Sagasta CL. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. American Journal of Medicine. 1987;83(5A):72-77.

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. American Journal of Clinical Nutrition. 2002;76:1177S-1182S.

Martinez-Chantar ML, Vazquez-Chantada M, Garnacho M, et al. S-adenosylmethionine regulates cytoplasmic HuR via AMP-activated kinase. Gastroenterology. 2006;131(1):223-232.

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. Journal of Hepatology. 1999;30(6):1081-1089.

Mato JM, Corrales FJ, Lu SC, Avila MA. S-Adenosylmethionine: a control switch that regulates liver function. FASEB J. 2002;16(1):15-26.

Matsui H, Kawada N. Effect of S-adenosyl-L-methionine on the activation, proliferation and contraction of hepatic stellate cells. European Journal of Pharmacology. 2005;509(1):31-36.

McClain CJ, Hill DB, Song Z, et al. S-Adenosylmethionine, cytokines, and alcoholic liver disease. Alcohol. 2002 Jul;27(3):185-92.

McHughes M, Lipman AG. Managing osteoarthritis pain when your patient fails simple analgesics and NSAIDs and is not a candidate for surgery. Current Rheumatology Reports. 2006;8(1):22-29.

McKillop IH, Schrum LW. Alcohol and liver cancer. Alcohol. 2005;35(3):195-203.

McMillan JM, Walle UK, Walle T. S-adenosyl-L-methionine: transcellular transport and uptake by Caco-2 cells and hepatocytes. Journal of Pharmacy and Pharmacology. 2005;57(5):599-605.

Mischoulon D. Update and critique of natural remedies as antidepressant treatments. Psychiatric Clinics of North America. 2007;30(1):51-68.

Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. American Journal of Clinical Nutrition. 2002;76:1158S-1161S.

Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. American Journal of Medicine. 1987;83(5A):81-83.

Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]. BMC Musculoskelet Disord. 2004 Feb 26;5:6.

Natural Medicines Comprehensive Database, Online Edition. Pharmacist's Letter/Prescriber's Letter. Stockton CA: Therapeutic Research Facility, 2006. Available at: http://www.pharmacistsletter.com/(S(ulqz3s45omt3ag55um4kj345))/home.aspx?li=1&st=1&cs=&s=ND.

Nguyen M, Gregan A. S-adenosylmethionine and depression. Australian Family Physician. 2002;31(4):339-343.

Pharmavite LLC. SAM-e. No date given. Available at: http://www.sam-e.com. Accessed October 27, 2003.

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(3):151-154.

Rambaldi A, Gluud C. S-adenosyl-L-methionine for alcoholic liver diseases. Cochrane Database Systematic Review. 2006 Apr 19;(2):CD002235.

Rambaldi A. Gluud C. S-adenosyl-L-methionine for alcoholic liver disease. Cochrane Database System Review. 2001;(4):CD002235.

Reichard JF, Schnekenburger M, Puga A. Long term low-dose arsenic exposure induces loss of DNA methylation. Biochemistry and Biophysics Research Communications. 2007;352(1):188-192.

Rosenbaum JF, Fava M, Falk WE, Pollack MH, Cohen LS, Cohen BM, Zubenko GS. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatrica Scandinavia. 1990;81(5):432-436.

Salmaggi P, Bressa GM, Nicchia G, Coniglio M, La Greca P, Le Grazie C. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychotherapy and Psychosomatics. 1993;59(1):34-40.

Scarpa S, Cavallaro RA, D'Anselmi F, Fuso A. Gene silencing through methylation: an epigenetic intervention on Alzheimer disease. Journal of Alzheimers Disease. 2006;9(4):407-414.

Shekim WO, Antun F, Hanna GL, McCracken JT, Hess EB. S-adenosyl-L-methionine (SAM) in adults with ADHD, RS: preliminary results from an open trial. Psychopharmacology Bulletin. 1990;26(2):249-253.

Shippy RA, Mendez D, Jones K, Cergnul I, Karpiak SE. S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS. BMC Psychiatry. 2004;4:38.

Silveri MM, Parow AM, Villafuerte RA, et al. S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects. Biology and Psychiatry. 2003;54(8):833-839.

Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM.. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. Journal of Family Practice. 2002;51(5):425-430.

Stramentinoli G, Gualano M, Galli-Kienle M. Intestinal absorption of S-adenosyl-L-methionine. Journal of Pharmacology and Experimental Therapeutics. 1979;209(3):323-326.

Strauss KA, Morton DH, Puffenberger EG, et al. Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency. Molecular and Genetic Metabolism. Epublished ahead of print. April 3, 2007.

Tan SV, Guiloff RJ. Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS. Journal of Neurology, Neurosurgery and Psychiatry. 1998;65(1):23-28.

Tavoni A, Vitali C, Bombardieri S, Pasero G. Evaluation of S-adenosylmethionine in primary fibromyalgia. A double-blind crossover study. American Journal of Medicine. 1987;83(5A):107-110.

Terneus MV, Kiningham KK, Carpenter AB, Sullivan SB, Valentovic MA. Comparison of S-Adenosyl-L-methionine and N-acetylcysteine protective effects on acetaminophen hepatic toxicity. Journal of Pharmacology and Experimental Therapeutics. 2007;320(1):99-107.

Vahora SA, Malek-Ahmasi P. S-adenosylmethionine in the treatment of depression. Neuroscience and Biobehavior Review. 1988;12(2):139-141.

Vendemiale G, Altomare E, Trizio T, et al. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scandinavian Journal of Gastroenterology. 1989;24(4):407-415.

Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. American Journal of Medicine. 1987; 83(5A):78-80.

Volkmann H, Norregaard J, Jacobsen S, Danneskiold-Samsoe B, Knoke G, Nehrdich D. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scandinavian Journal of Rheumatology. 1997;26(3):206-211.

Wang X, Cederbaum AI. S-adenosyl-l-methionine attenuates hepatotoxicity induced by agonistic Jo2 Fas antibody following CYP2E1 induction in mice. Journal of Pharmacology and Experimental Therapeutics. 2006;317(1):44-52.

Werneke U, Turner T, Priebe S. Complementary medicines in psychiatry: review of effectiveness and safety. British Journal of Psychiatry. 2006;188:109-121.

Williams KT, Schalinske KL. New insights into the regulation of methyl group and homocysteine metabolism. Journal of Nutrition. 2007;137(2):311-314.

Wu D, Cederbaum AI. Opposite action of S-adenosyl methionine and its metabolites on CYP2E1-mediated toxicity in pyrazole-induced rat hepatocytes and HepG2 E47 cells. American Journal of Physiology – Gastrointestinal and Liver Physiology. 2006;290(4):G674-G684.

Last Revised May 25, 2007

Note: The above information is not intended to replace the advice of your physician, pharmacist, or other healthcare professional. It is not meant to indicate that the use of the product is safe, appropriate, or effective for you.

In general, herbal products are not subject to review or approval by the U.S. Food and Drug Administration (FDA). They are not required to be standardized, meaning that the amounts of active ingredients or contaminants they contain may vary between brands or between different batches of the same brand. Not all of the risks, side effects, or interactions associated with the use of herbal products are known because few reliable studies of their use in humans have been done.

This information is provided for your education only. Please share this information with your healthcare provider and be sure that you talk to your doctor and pharmacist about all the prescription and non-prescription medicines you take before you begin to use any herbal product.

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