SAM-e

SAM-e

SAM-e

Common Names

  • SAM-e

For Patients & Caregivers

Not enough research has been performed to say whether SAMe can treat depression or osteoarthritis.

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.
  • You are taking clomipramine: There is one report of serotonin syndrome in a woman after simultaneous use of clomipramine and SAMe.
  • Headache
  • Mild stomach upset
  • Flatulence
  • Nausea and vomiting
  • Patients with bipolar disorder may develop manic phase
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For Healthcare Professionals

S-adenosylmethionine

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 were unresponsive to serotonin reuptake inhibitors (16); it also improved memory-related cognitive symptoms in such patients (17). In other studies, addition of SAMe to pegylated interferon alpha (pegIFN alpha) and ribavirin improved viral response in patients with chronic hepatitis C (18); and postoperative SAMe therapy may benefit residual liver function in patients with cirrhosis (19).

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.

  • AIDS-related myelopathy
  • Alzheimer’s disease
  • Bursitis
  • Cirrhosis
  • Depression
  • Muscle pain
  • Osteoarthritis

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)

Reported: Headache, mild GI upset, flatulence, nausea, vomiting.
Patients with bipolar disorder may develop manic phase.
(11)

Clomipramine: Serotonin syndrome was reported following concomitant administration of clomipramine and intramuscular S-adenosylmethionine (13).


  1. Baldessarini RJ. Neuropharmacology of S-adenosyl-L-methionine. Am J Med 1987;83:60-5.

  2. Bell KM, et al. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl 1994;154:15-8.

  3. Reynolds EH, Carney MW, Toone BK. Methylation and mood. Lancet 1984;2:196-8.

  4. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;2:137-52.

  5. Cohen BM, Satlin A, Zubenko GS. S-adenosyl-L-methionine in the treatment of Alzeheimer’s disease. J Clin Psychopharmacol l988;8:43-7.

  6. Iruela LM, et al. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522.

  7. 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]

  8. 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.

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