Health Care Professional Information
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).
- AIDS-related myelopathy
- Alzheimer's disease
- Muscle pain
- Sulfur-containing compound to stabilize molecule: Tosylate, disulfate tosylate, disulfate ditosylate, or 1,4-butanedisulfonate
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)
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)
Reported: Headache, mild GI upset, flatulence, nausea, vomiting.
Patients with bipolar disorder may develop manic phase.
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.
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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- 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.
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.
- 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.
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.
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.
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).
- Mild stomach upset
- Nausea and vomiting
- Patients with bipolar disorder may develop manic phase
Last updated: October 12, 2011