S-Adenosylmethionine (SAMe)
What is it? Overview Usage Side Effects and Warnings

S-Adenosylmethionine (SAMe) Side Effects and Warnings

Written by FoundHealth.

Safety Issues

SAMe appears to be quite safe, according to both human and animal studies. 1 2 3 4 The most common side effect is mild digestive distress. However, SAMe does not actually damage the stomach. 5 Like other substances with antidepressant activity, SAMe might trigger a manic episode in those with bipolar disease (manic-depressive illness). 6 7 Safety in young children, pregnant or nursing women, or those with severe liver or kidney disease has not been established.

SAMe might interfere with the action of the Parkinson's drug levodopa. 8 In addition, there may also be risks involved in combining SAMe with standard antidepressants. 9 For this reason, you shouldn't try either combination except under physician supervision.

Interactions You Should Know About

If you are taking:

  • Standard antidepressants, including MAO inhibitors , SSRIs , and tricyclics : Do not take SAMe except on a physician's advice.
  • Levodopa for Parkinson's disease: SAMe might help relieve the side effects of this drug. However, it might also reduce its effectiveness over time.


  1. Cozens DD, Barton SJ, Clark R, Gibson WA, Hughes EW, Masters RE, Offer JM, Perkin CJ, Stramentinoli G. Reproductive toxicity studies of ademetionine. Arzneimittelforschung. 38(11):1625-9.
  2. 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. 83(5A):84-8.
  3. Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med. 1987;83(5A):89-94.
  4. Caruso I, Peitrogrande 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.
  5. di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med. 83(5A):60-5.
  6. Carney MW, Chary TK, Bottiglieri T, Reynolds EH. The switch mechanism and the bipolar/unipolar dichotomy. Br J Psychiatry. 154():48-51.
  7. Carney MW, Chary TK, Bottiglieri T, Reynolds EH. Switch and S-adenosylmethionine. Ala J Med Sci. 25(3):316-9.
  8. Liu X, Lamango N, Charlton C. L-dopa depletes S-adenosylmethionine and increases S-adenosyl homocysteine: Relationship to the wearing-off effects [abstract]. Soc Neurosci Abstracts. 1998;24:1469.
  9. Iruela LM, Minguez L, Merino J, et al. Toxic interaction of S-adenosylmethionine and clomipramine [letter]. Am J Psychiatry. 1993;150:522.


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