Health Care Professional Information
Clinical Summary
An endogenously produced compound in the human body, SAMe is produced from adenosine triphosphate and methionine (1) (2). In the United States, oral supplementation is used primarily to treat depression (6) and arthritis (5) (7), but data are conflicting. SAMe was shown effective in patients with major depressive disorder who do not respond to serotonin reuptake inhibitors (16); it also improves memory-related cognitive symptoms in such patients (17). Addition of SAMe to pegylated interferon alpha (pegIFN alpha) and ribavirin improved viral response in patients with chronic hepatitis C (18).
Because it is poorly absorbed, enteric-coated tablets are preferred. Outside the United States, parenteral formulations are used to treat fibromyalgia (9), osteoarthritis (14) (15) and tendonitis as well as depression.
Adverse effects, such as nausea and diarrhea, have been reported following initiation of oral therapy. Dosage should be titrated up over at least 1 to 2 weeks. Patients who are diagnosed with bipolar disorder should not take this supplement (11). There may be a risk of serotonin syndrome when administered with prescription antidepressants (e.g., selective serotonin reuptake inhibitors, MAO inhibitors, or tricyclics) (13).
Purported Uses
- AIDS-related myelopathy
- Alzheimer's disease
- Bursitis
- Cirrhosis
- Depression
- Muscle pain
- Osteoarthritis
Constituents
- S-adenosylmethionine
- Sulfur-containing compound to stabilize molecule: Tosylate, disulfate tosylate, disulfate ditosylate, or 1,4-butanedisulfonate
(1)
Mechanism of Action
SAMe is endogenously produced from adenosine triphosphate and the amino acid methionine. It is a major, ubiquitous methyl donor to a wide variety of molecules, including catecholamines and other biogenic amines, fatty acids, neurotransmitters, nucleic acids, polysaccharides, porphyrins, proteins and membrane phospholipids. Homocysteine is formed through the transsulfuration pathway and is catabolized to cysteine and indirectly to glutathione. The mechanism by which SAMe treats depression is unknown. However, some researchers believe that it increases the synthesis of neurotransmitters such as serotonin, norepinephrine and dopamine, thus increasing the responsiveness of neurotransmitter receptors and increasing the fluidity of cell membranes through the production of phospholipids.
(2) (3) (4)
Pharmacokinetics
Following oral administration of enteric-coated tablet, peak plasma concentrations were obtained within 3-6 hours. There is extensive first-pass hepatic metabolism and the elimination half-life has been reported to be 1.7 hours. Volume of distribution has been calculated to be 0.4 L/kg and there is no significant protein binding. S-adenosylmethionine crosses the blood-brain barrier as well as the placenta. Sixteen percent of a dose is excreted in the urine in 48 hours, and 24% is excreted in feces in 72 hours.
(3) (4) (12)
Adverse Reactions
Reported: Headache, mild GI upset, flatulence, nausea, vomiting.
Patients with bipolar disorder may develop manic phase.
(11)
Herb-Drug Interactions
Selective serotonin reuptake inhibitors (SSRIs): SAMe may increase the risk of serotonin syndrome when administered together.
Monoamine oxidase inhibitors (MAO-Is): SAMe may increase the risk of serotonin syndrome when given concomitantly.
Tricyclics: SAMe may increase the risk of serotonin syndrome when administered concurrently.
Clomipramine: Serotonin syndrome was reported following concomitant administration of clomipramine and intramuscular S-adenosylmethionine.
(13)
Literature Summary and Critique
Most clinical findings of SAMe involve parenteral formulations. Oral studies were typically open trials, and double-blind studies involved small sample size. SAMe's absorption from the GI tract is questionable so it is not valid to compare parenterally administered results with the oral forms. The parenteral formulation has been shown to be more effective. Oral studies of SAMe for depression are controversial, small, and flawed. Further research is needed to determine if oral SAMe is an effective treatment for depression.
Dosage (Inside MSKCC Only)
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References
- Osteoarthritis: the clinical picture, pathogenesis, and management with studies on a new therapeutic agent, S-adenosylmethionine. Proceedings of a symposium. Am J Med 1987;83:1-110.
- Baldessarini RJ. Neuropharmacology of S-adenosyl-L-methionine. Am J Med 1987;83:60-5.
- Stramentinoli G. Pharmacologic aspects of S-adenosylmethionine. Pharmacokinetics and pharmacodynamics. Am J Med 1987;83:35-42.
- Bell KM, et al. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl 1994;154:15-8.
- di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med 1987;83:95-103.
- Reynolds EH, Carney MW, Toone BK. Methylation and mood. Lancet 1984;2:196-8.
- Bradley JD, 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.
- Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;2:137-52.
- Volkmann H, et al. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scand J Rheumatol l997;26:206-11.
- Cohen BM, Satlin A, Zubenko GS. S-adenosyl-L-methionine in the treatment of Alzeheimer's disease. J Clin Psychopharmacol l988;8:43-7.
- 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.
- Osman E, Owen JS, Burroughs AK. S-adenosyl-L-methionine — a new therapeutic agent in liver disease? (Review article). Aliment Pharmacol Ther 1993;7:21-8.
- Iruela LM, et al. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522.
- Caruso I, et al. Italian double blind multicenter study comparing S-adenosylmethionine, naproxen and placebo in the treatment of degenerative joint disease. Am J Med 1987;83:66-71.
- Maccagno A. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 1987;83:72-7.
- Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M. 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 Aug;167(8):942-8.
- Levkovitz Y, Alpert JE, Brintz CE, et al. Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. J Affect Disord. 2011 Sep 10. [Epub ahead of print]
- Filipowicz M, Bernsmeier C, Terracciano L, et al. S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse. PLoS One. 2010 Nov 8;5(11):e15492.
Consumer Information
How It Works
Bottom Line: Not enough research has been performed to say whether SAMe can treat depression or osteoarthritis. It should not be used to treat Alzheimer's disease or any other medical condition.
SAMe is a molecule that is produced naturally by the human body. It acts on a number of important molecules in the body, including hormones, neurotransmitters, fatty acids, DNA, proteins, and cell membrane molecules. It has been found to have anti-inflammatory activity. Scientists are uncertain how SAMe works in depression, but they believe it may be linked to synthesis of neurotransmitters such as serotonin and dopamine.
Purported Uses
- To treat AIDS-related myelopathy (spinal cord disease)
No scientific evidence supports this use.
- To treat Alzheimer's disease
There are no data to back this claim.
- To treat bursitis
Laboratory studies show that SAM-e has anti-inflammatory activity, but human data are lacking.
- To treat cirrhosis of the liver
No scientific evidence supports this use.
- To treat depression
Clinical studies produced conflicting results or were poorly designed; more studies are needed to evaluate this use.
- To treat fibromyalgia
No scientific evidence supports this use.
- To treat osteoarthritis
One clinical trial showed that oral SAMe is as effective as conventional treatments in treating osteoarthritis.
Research Evidence
Most clinical trials conducted with SAMe have used the injected formulation, which has generally been shown to be more effective than SAMe taken by mouth. Scientists are uncertain whether SAMe is absorbed effectively through the intestine into the bloodstream. Therefore, we cannot infer from trials that use injected SAMe whether oral SAMe would work for the same medical condition.
Depression:
In general, clinical studies using oral SAMe to treat depression have been controversial, small, and flawed. It is still unclear whether oral SAMe is effective in treating depression, and further research on this topic should be conducted.
Osteoarthritis:
SAMe was compared to a conventional therapy for osteoarthritis in a clinical trial with 734 patients. Patients randomly received either 1200 mg/day of oral SAMe, 750 mg/day of naproxen (an NSAID), or a placebo pill. At the end of the trial, SAMe and naproxen appeared equally effective in improving patients' symptoms, and SAMe caused fewer side effects than naproxen.
The effectiveness of SAMe in treating osteoarthritis was studied in a clinical trial with 45 patients. For 84 days, patients were randomly assigned to take either 1200 mg/day of SAMe or 20 mg/day of piroxicam. The results showed similar effectiveness between the two treatments, with an equal number of side effects. However, patients taking SAMe reported that their improvement lasted longer after the treatment was stopped.
Do Not Take If
- You are taking selective serotonin reuptake inhibitors (SSRIs) (Taking SAMe at the same time may increase the risk of serotonin syndrome, a condition resulting from high serotonin levels and characterized by euphoria, drowsiness, rapid muscle contraction of the eye, ankle, jaw, clumsiness, restlessness, sweating, intoxication, muscle twitching, rigidity, high body temperature, shivering, diarrhea, loss of consciousness and death).
- You are taking monoamine oxidase inhibitors (MAO-Is) (Taking SAMe at the same time may increase the risk of serotonin syndrome.)
- You are taking tricyclic antidepressants (Taking SAMe at the same time may increase the risk of serotonin syndrome.)
- You are taking clomipramine (There is one report of serotonin syndrome in a woman after simultaneous use of clomipramine and SAMe).
Side Effects
- Headache
- Mild stomach upset
- Flatulence
- Nausea and vomiting
- Patients with bipolar disorder may develop manic phase
Last updated: October 12, 2011
absorption (ub-SORP-shun)
The process of taking nutrients from the digestive system into the blood so they can be used in the body.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)acid (A-sid)
A chemical that gives off hydrogen ions in water and forms salts by combining with certain metals. Acids have a sour taste and turn certain dyes red. Some acids made by the body, such as gastric acid, can help organs work the way they should. An example of an acid is hydrochloric acid. Acidity is measured on a scale called the pH scale. On this scale, a value of 7 is neutral, and a pH value of less than 7 to 0 shows increasing acidity.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)adenosine triphosphate (uh-DEH-nuh-seen try-FOS-fayt)
A substance present in all living cells that provides energy for many metabolic processes and is involved in making RNA. Adenosine triphosphate made in the laboratory is being studied in patients with advanced solid tumors to see if it can decrease weight loss and improve muscle strength. Also called ATP.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)administration (ad-MIH-nih-STRAY-shun)
In medicine, the act of giving a treatment, such as a drug, to a patient. It can also refer to the way it is given, the dose, or how often it is given.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)anti-inflammatory (AN-tee-in-FLA-muh-TOR-ee)
Having to do with reducing inflammation.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)arthritis (ar-THRY-tis)
A disease that causes inflammation and pain in the joints.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)barrier (BAYR-ee-er)
Something that blocks, prevents, separates, or limits.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)cell (sel)
The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)chronic (KRAH-nik)
A disease or condition that persists or progresses over a long period of time.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)clinical (KLIH-nih-kul)
Having to do with the examination and treatment of patients.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)clinical trial (KLIH-nih-kul TRY-ul)
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)concomitant (kon-KAH-mih-tunt)
Occurring or existing at the same time as something else. In medicine, it may refer to a condition a person has or a medication a person is taking that is not being studied in the clinical trial he or she is taking part in.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)condition (kun-DIH-shun)
In medicine, a health problem with certain characteristics or symptoms.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)conventional therapy (kun-VEN-shuh-nul THAYR-uh-pee)
A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)depression (dee-PREH-shun)
A mental condition marked by ongoing feelings of sadness, despair, loss of energy, and difficulty dealing with normal daily life. Other symptoms of depression include feelings of worthlessness and hopelessness, loss of pleasure in activities, changes in eating or sleeping habits, and thoughts of death or suicide. Depression can affect anyone, and can be successfully treated. Depression affects 15-25% of cancer patients.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)diarrhea (dy-uh-REE-uh)
Frequent and watery bowel movements.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)disorder (dis-OR-der)
In medicine, a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)DNA
The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)donor (DOH-ner)
In medicine, a person who gives blood, cells, tissue, or an organ for use in another person, such as in a blood transfusion or an organ transplant.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)dose (dose)
The amount of medicine taken, or radiation given, at one time.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)euphoria (yoo-FOR-ee-uh)
A feeling of great happiness or well-being. Euphoria may be a side effect of certain drugs.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)feces (FEE-seez)
The material in a bowel movement. Feces is made up of undigested food, bacteria, mucus, and cells from the lining of the intestines. Also called stool.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)GI
Refers to the stomach and intestines. Also called gastrointestinal.
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(http://www.cancer.gov/dictionary)glutathione (GLOO-tuh-THY-one)
A substance found in plant and animal tissues that has many functions in a cell. These include activating certain enzymes and destroying toxic compounds and chemicals that contain oxygen.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)hepatic (heh-PA-tik)
Refers to the liver.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)hepatitis (HEH-puh-TY-tis)
Disease of the liver causing inflammation. Symptoms include an enlarged liver, fever, nausea, vomiting, abdominal pain, and dark urine.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)interferon (in-ter-FEER-on)
A biological response modifier (a substance that can improve the body's natural response to infections and other diseases). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. The body normally produces these substances. They are also made in the laboratory to treat cancer and other diseases.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)intestine (in-TES-tin)
The long, tube-shaped organ in the abdomen that completes the process of digestion. The intestine has two parts, the small intestine and the large intestine. Also called bowel.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)intramuscular (IN-truh-MUS-kyoo-ler)
Within or into muscle. Also called IM.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)membrane (MEM-brayn)
A very thin layer of tissue that covers a surface.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)metabolism (meh-TA-buh-lih-zum)
The chemical changes that take place in a cell or an organism. These changes make energy and the materials cells and organisms need to grow, reproduce, and stay healthy. Metabolism also helps get rid of toxic substances.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)molecule (MAH-leh-kyool)
The smallest particle of a substance that has all of the physical and chemical properties of that substance. Molecules are made up of one or more atoms. If they contain more than one atom, the atoms can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)naproxen (nuh-PROK-sen)
A drug used to treat mild pain and the symptoms of arthritis and several other conditions. It is also being studied in the treatment of bone pain in patients with cancer. Naproxen stops the body from making substances that cause pain and inflammation. It is a type of nonsteroidal anti-inflammatory drug (NSAID) and a type of cyclooxygenase inhibitor. Also called Naprosyn.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)nausea (NAW-zee-uh)
A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side effect of some types of cancer therapy.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)neurotransmitter (NOOR-oh-tranz-MIH-ter)
A chemical that is made by nerve cells and used to communicate with other cells, including other nerve cells and muscle cells.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)norepinephrine (NOR-eh-pih-NEH-frin)
A chemical made by some nerve cells and in the adrenal gland. It can act as both a neurotransmitter (a chemical messenger used by nerve cells) and a hormone (a chemical that travels in the blood and controls the actions of other cells or organs). Norepinephrine is released from the adrenal gland in response to stress and low blood pressure. Also called noradrenaline.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)oral (OR-ul)
By or having to do with the mouth.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)placebo (pluh-SEE-boh)
An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)placenta (pluh-SEN-tuh)
The organ that nourishes the developing fetus in the uterus.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)plasma (PLAZ-muh)
The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)prescription (prih-SKRIP-shun)
A doctor's order for medicine or another intervention.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)protein (PROH-teen)
A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)response (reh-SPONTS)
In medicine, an improvement related to treatment.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)ribavirin (RY-buh-VY-rin)
A drug used to treat respiratory syncytial virus (RSV) infection in the lungs.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)serotonin (SAYR-uh-TOH-nin)
A hormone found in the brain, platelets, digestive tract, and pineal gland. It acts both as a neurotransmitter (a substance that nerves use to send messages to one another) and a vasoconstrictor (a substance that causes blood vessels to narrow). A lack of serotonin in the brain is thought to be a cause of depression. Also called 5-hydroxytryptamine.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)significant (sig-NIH-fih-kunt)
In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)stomach (STUH-muk)
An organ that is part of the digestive system. The stomach helps digest food by mixing it with digestive juices and churning it into a thin liquid.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)supplementation (SUH-pleh-men-TAY-shun)
Adding nutrients to the diet.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)syndrome (SIN-drome)
A set of symptoms or conditions that occur together and suggest the presence of a certain disease or an increased chance of developing the disease.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)therapy (THAYR-uh-pee)
Treatment.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)urine (YOOR-in)
Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)viral (VY-rul)
Having to do with a virus.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)
