SAMe

Also indexed as: S-adenosyl-L-methionine, S-adenosylmethionine

What does it do? SAMe is an important biological agent in the human body, participating in over 40 essential biochemical reactions. SAMe participates in detoxification reactions and in the manufacture of brain chemicals, antioxidants, joint tissue structures, and many other important components.1 2

SAMe appears to raise levels of dopamine, an important neurotransmitter in mood regulation,3 and higher SAMe levels in the brain are associated with successful drug treatment of depression.4 Oral SAMe has been demonstrated to be an effective treatment for depression in some,5 6 7 8 though not all,9 double-blind studies. While it does not seem to be as powerful as full amounts of antidepressant medications 10 or St. John’s wort, its effects are felt more rapidly, often within one week.11

SAMe possesses anti-inflammatory, pain-relieving, and tissue-healing properties that may help protect the health of joints.12 13 Several double-blind studies have shown that SAMe is useful for people with osteoarthritis, reducing pain, stiffness, and swelling better than placebos and equal to drugs such as ibuprofen and naproxen.14 15 16 17 18 19 20 21

Intravenous SAMe given to fibromyalgia patients reduced pain and depression in two double-blind studies,22 23 but in a short (ten-day) trial no benefit was seen.24 Oral SAMe was tested in one double-blind study and significant beneficial effects were noticed, such as reduced pain, fatigue, and stiffness, and improved mood.25

Oral and intravenous treatment with SAMe replenishes important substances in damaged livers and improves the flow of bile.26 27 Preliminary research has indicated that SAMe may be helpful in a variety of liver conditions, including cholestasis, Gilbert’s syndrome, alcoholic liver injury, and cirrhosis.28 29 30 In alcoholic cirrhosis, damage to the liver prevents the natural formation of SAMe from the amino acid methionine. In a double-blind trial, people with cirrhosis of the liver due to alcoholism who took SAMe for two years had a 47% lower rate of death or need for liver transplantation, compared with those who received a placebo.31 However, the improvement did not quite achieve statistical significance. In people with less severe cirrhosis, the results were more impressive and were also statistically significant.

Preliminary research also suggests oral SAMe may increase sperm activity in infertile men 32 and may be helpful in the treatment of migraine headaches.33 One double-blind study found injections of SAMe significantly more helpful than placebo injections for reducing the symptoms of post-concussion syndrome.34

Where is it found? SAMe is not abundant in the diet, though its precursor, the amino acid, methionine, is plentiful in many protein foods. It is not known whether increasing one’s intake of methionine will increase the body’s production of SAMe. Supplements of SAMe have been available in the U.S. since 1997.

SAMe has been used in connection with the following conditions (refer to the individual health concern for complete information):

Rating Health Concerns
3Stars Liver cirrhosis
Osteoarthritis
2Stars Depression
Fibromyalgia
Hepatitis (for liver cholestasis)
Pregnancy and postpartum support (for cholestasis only)
1Star Bipolar disorder
Infertility (male)
Migraine headaches
Post-concussion syndrome
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

Who is likely to be deficient? SAMe is normally produced in the liver from the amino acid, methionine, which is abundant in most diets. Folic acid and vitamin B12 are necessary for the synthesis of SAMe, and deficiencies of these vitamins results in low concentrations of SAMe in the central nervous system.35 Low blood or central nervous system levels of SAMe have been detected in people with cirrhosis of the liver,36 coronary heart disease,37 Alzheimer’s disease, and depression.38

How much is usually taken? Healthy people do not need to take this supplement. Researchers working with people suffering from a variety of conditions have been using these amounts of SAMe: depression, 1,600 mg per day; osteoarthritis, 800–1,200 mg per day; fibromyalgia, 800 mg per day; liver disorders, 1,200 mg per day; and migraine, 800 mg per day.

Are there any side effects or interactions? Clinical trials in thousands of people for up to two years have demonstrated that SAMe is very well tolerated, much better than the medications with which it has often been compared.39 40 Occasional gastrointestinal upset may be experienced by some people. Researchers treating people with bipolar disorder (manic depression) have reported that SAMe could cause them to switch from depression to a manic episode.41 42

Use of SAMe may be detrimental to people with Parkinson’s disease. Animal studies indicate that excessive methylation (methylation is one of the biochemical reactions promoted by SAMe) is associated with Parkinson’s disease43 and SAMe has caused Parkinson’s disease-like effects in animal studies.44 Both animal and human studies indicate that increased methylation can cause the depletion of dopamine and block the effects of L-dopa 45 46 47 —changes that in theory should exacerbate symptoms of Parkinson’s disease. Preliminary evidence indicates that SAMe may improve the emotional depression and the impaired mental function that is often associated with Parkinson’s disease.48 Nonetheless, many healthcare professionals recommend that patients with Parkinson’s disease avoid supplementing with SAMe until more is known.

Are there any drug interactions? Certain medications may interact with SAMe. Refer to the drug interactions safety check for a list of those medications.

References:

1. Chiang PK, Gordon RK, Tal J, et al. S-Adenosylmethionine and methylation. FASEB J 1996;10:471–80 [review].

2. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137–52 [review].

3. Fava M, Rosenbaum JF, MacLaughlin R, et al. Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant. J Psychiatr Res 1990;24:177–84.

4. Bell KM, Potkin SG, Carreon D, Plon L. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand 1994;154(suppl):15–8.

5. Bell KM, Potkin SG, Carreon D, Plon L. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand 1994;154(suppl):15–8.

6. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: Meta-analysis of clinical studies. Acta Neurol Scand 1994;154(suppl):7–14.

7. Salmaggi P, Bressa GM, Nicchia G, et al. Double-blind, placebo-controlled study of s-adenosyl-methionine in depressed post-menopausal women. Psychother Psychosom 1993;59:34–40.

8. Kagan BL, Sultzer DL, Rosenlicht N, et al. Oral S-adenosyl-methionine in depression: A randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147:591–5.

9. Fava M, Rosenbaum JF, Birnbaum R, et al. The thyrotropin-releasing hormone as a predictor of response to treatment in depressed outpatients. Acta Psychiatr Scand 1992;86:42–5.

10. De Vanna M, Rigamonti R. Oral S-adenosyl-L-methionine in depression. Curr Ther Res 1992;52:478–85.

11. Fava M, Giannelli A, Rapisarda V. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. Psychiatr Res 1995;56:295–7.

12. Schumacher HR. Osteoarthritis: The clinical picture, pathogenesis, and management with studies on a new therapeutic agent, S-adenosylmethionine. Am J Med 1987;83(suppl 5A):1–4 [review].

13. Harmand MF, Vilamitjana J, Maloche E, et al. Effects of S-adenosylmethionine on human articular chondrocyte differentiation: an in vitro study. Am J Med 1987;83(suppl 5A):48–54.

14. Domljan Z, Vrhovac B, Durrigl T, Pucar I. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 1989;27:329–33.

15. Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine in versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987;83(suppl 5A):81–3.

16. Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83(suppl 5A):78–80.

17. Maccagno A. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 1987;83(suppl 5A):72–7.

18. Caruso I, Pietrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987;83(suppl 5A):66–71.

19. Marcolongo R, Giordano N, Colombo B, et al. Double-blind multicentre study of the activity of s-adenosyl-methionine in hip and knee osteoarthritis. Curr Ther Res 1985;37:82–94.

20. Glorioso S, Todesco S, Mazzi A, et al. Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 1985;5:39–49.

21. Montrone F, Fumagalli M, Sarzi Puttini P, et al. Double-blind study of S-adenosyl-methionine versus placebo in hip and knee arthrosis. Clin Rheumatol 1985;4:484–5.

22. Tavoni A, Jeracitano G, Cirigliano G. Evaluation of S-adenosylmethionine in secondary fibromyalgia: a double-blind study. Clin Exp Rheumatol 1998;16:106–7 [letter].

23. Tavoni A, Vitali C, Bombardieri S, et al. Evaluation of S-adenosylmethionine in primary fibromyalgia: a double-blind crossover study. Am J Med 1987;83(suppl 5A):107–10.

24. Volkmann H, Norregaard J, Jacobsen S, et al. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scand J Rheumatol 1997;26:206–11.

25. Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia: double-blind clinical evaluation. Scand J Rheumatol 1991;20:294–302.

26. Lieber CS. Herman Award lecture, 1993: a personal perspective on alcohol, nutrition, and the liver. Am J Clin Nutr 1993;58:430–42 [review].

27. Osman E, Owen JS, Burroughs AK. S-adenosyl-L-methionine–a new therapeutic agent in liver disease? Aliment Pharmacol Ther 1993;7:21–8 [review].

28. Angelico M, Gandin C, Nistri A, et al. Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis. Scand J Clin Lab Invest 1994;54:459–64.

29. Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosyl-methionine in the symptomatic treatment of intrahepatic cholestasis: a double-blind, placebo-controlled study. Gastroenterology 1990;99:211–5.

30. Bombardieri G, Milani A, Bernardi L, Rossi L. Effects of S-adenosyl-L-methionine (SAMe) in the treatment of Gilbert’s syndrome. Curr Ther Res 1985;37:580–5.

31. Mato JM, Cámara J, Fernández J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999;30:1081–9.

32. Piacentino R, Malara D, Zaccheo F, et al. Preliminary study of the use of s. adenosyl methionine in the management of male sterility. Minerva Ginecol 1991;43:191–3 [in Italian].

33. Gatto G, Caleri D, Michelacci S, Sicuteri F. Analgesizing effect of a methyl donor (S-adenosylmethionine) in migraine: an open clinical trial. Int J Clin Pharmacol Res 1986;6:15–7.

34. Ballerini FB, Anguera AL, Alcaraz P, et al. SAM in the management of postconcussional syndrome. Med Clin (Barc) 1983;80:161–4.

35. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137–52 [review].

36. Osman E, Owen JS, Burroughs AK. S-adenosyl-L-methionine–a new therapeutic agent in liver disease? Aliment Pharmacol Ther 1993;7:21–8 [review].

37. Loehrer FM, Angst CP, Haefeli WE, et al. Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease. Arterioscler Thromb Vasc Biol 1996;16:727–33.

38. Bottiglieri T, Godfrey P, Flynn T, et al. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 1990;53:1096–8.

39. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand 1994;154(suppl):7–14.

40. Di Padova C. S-adenosyl-methionine in the treatment of osteoarthritis: review of the clinical studies. Am J Med 1987;83(suppl 5A):60–4.

41. Carney MWP, Chary TK, Bottiglieri T, et al. The switch mechanism and the bipolar/unipolar dichotomy. Br J Psychiatry 1989;154:48–51.

42. Carney MWP, Chary TK, Bottiglieri T, et al. Switch and S-adenosyl-methionine. Alabama J Med Sci 1988;25:316–9.

43. Charlton CG, Mack J. Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain. Support for an excess methylation hypothesis for parkinsonism. Mol Neurobiol 1994;9:149–61.

44. 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. Behav Neural Biol 1993;59:186–93.

45. Benson R, Crowell B, Hill B, et al. The effects of L-dopa on the activity of methionine adenosyltransferase: relevance to L-dopa therapy and tolerance. Neurochem Res 1993;18:325–30.

46. Cheng H, Gomes-Trolin C, Aquilonius SM, et al. Levels of L-methionine S-adenosyltransferase activity in erythrocytes and concentrations of S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with Parkinson’s disease. Exp Neurol 1997;145:580–5.

47. Charlton CG, Crowell B Jr. Parkinson’s disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav 1992;43:423–31.

48. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137–52 [review].