Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2009 Oct 7;2009(4):CD007321.
doi: 10.1002/14651858.CD007321.pub2.

S-Adenosylmethionine for osteoarthritis of the knee or hip

Anne Ws Rutjes  1 , Eveline Nüesch, Stephan Reichenbach, Peter Jüni
Affiliations
Meta-Analysis

S-Adenosylmethionine for osteoarthritis of the knee or hip

Anne Ws Rutjes et al. Cochrane Database Syst Rev. .

Abstract

Background: Osteoarthritis is the most common form of joint disease and the leading cause of pain and disability in the elderly. S-Adenosylmethionine may be a viable treatment option but the evidence about its effectiveness and safety is equivocal.

Objectives: We set out to compare S-Adenosylmethionine (SAMe) with placebo or no specific intervention in terms of effects on pain and function and safety outcomes in patients with knee or hip osteoarthritis.

Search strategy: We searched CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5 August 2008, checked conference proceedings and reference lists, and contacted authors.

Selection criteria: Randomised or quasi-randomised controlled trials that compared SAMe at any dosage and in any formulation with placebo or no intervention in patients with osteoarthritis of the knee or hip.

Data collection and analysis: Two independent authors extracted data using standardised forms. We contacted investigators to obtain missing outcome information. We calculated standardised mean differences (SMDs) for pain and function, and relative risks for safety outcomes. We combined trials using inverse-variance random-effects meta-analysis.

Main results: Four trials including 656 patients were included in the systematic review, all compared SAMe with placebo. The methodological quality and the quality of reporting were poor. For pain, the analysis indicated a small SMD of -0.17 (95% CI -0.34 to 0.01), corresponding to a difference in pain scores between SAMe and placebo of 0.4 cm on a 10 cm VAS, with no between trial heterogeneity (I(2) = 0). For function, the analysis suggested a SMD of 0.02 (95% CI -0.68 to 0.71) with a moderate degree of between-trial heterogeneity (I2 = 54%). The meta-analyses of the number of patients experiencing any adverse event, and withdrawals or drop-outs due to adverse events, resulted in relative risks of 1.27 (95% CI 0.94 to 1.71) and 0.94 (95% CI 0.48 to 1.86), respectively, but confidence intervals were wide and tests for overall effect were not significant. No trial provided information concerning the occurrence of serious adverse events.

Authors' conclusions: The current systematic review is inconclusive, hampered by the inclusion of mainly small trials of questionable quality. The effects of SAMe on both pain and function may be potentially clinically relevant and, although effects are expected to be small, deserve further clinical evaluation in adequately sized randomised, parallel-group trials in patients with knee or hip osteoarthritis. Meanwhile, routine use of SAMe should not be advised.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

1
1
Study flow chart
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Forest plot of 2 trials comparing the effects of S‐Adenosylmethionine and control (placebo or no intervention) on knee or hip pain. Values on x‐axis denote standardised mean differences.
4
4
Forest plot of 3 trials comparing the effects of S‐Adenosylmethionine and control (placebo or no intervention) on function. Values on x‐axis denote standardised mean differences.
5
5
Forest plot of 4 trials comparing patients experiencing any adverse event between S‐adenosylmethionine and control (placebo or no intervention). Values on x‐axis denote risks ratios.
6
6
Forest plot of 4 trials comparing patients who withdrew because of adverse events between S‐adenosylmethionine and control (placebo or no intervention). Values on x‐axis denote risks ratios.
1.1
1.1. Analysis
Comparison 1 S‐Adenosylmethionine versus placebo, Outcome 1 Pain.
1.2
1.2. Analysis
Comparison 1 S‐Adenosylmethionine versus placebo, Outcome 2 Function.
1.3
1.3. Analysis
Comparison 1 S‐Adenosylmethionine versus placebo, Outcome 3 Number of patients experiencing any adverse event.
1.4
1.4. Analysis
Comparison 1 S‐Adenosylmethionine versus placebo, Outcome 4 Number of patients who withdrew because of adverse events.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD007321

References

References to studies included in this review

Bradley 1994 {published data only}
    1. Bradley JD, Flusser D, Katz BP, Schumacher HR Jr, Brandt KD, Chambers MA, 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. Journal of Rheumatology 1994;21(5):905‐11. - PubMed
Caruso 1987 {published data only}
    1. Caruso I, Pietrogrande V, Caruso I, Pietrogrande V. Italian double‐blind multicenter study comparing S‐adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. American Journal of Medicine 1987;83(5A):66‐71. - PubMed
König 1990 {published data only}
    1. König H, Saal J. Quantitatively evaluated magnetic resonance tomography as a therapeutic follow‐up of the nonsteroidal antirheumatic ademetionin: a pilot study in patients with gonarthrosis [Quantitativ ausgewertete Kernspintomographie als Therapiekontrolle des nicht‐steroidalen Antirheumatikums Ademetionin: Pilotstudie bei Gonarthrose‐Patienten]. Rofo: Fortschritte auf dem Gebiet der Röntgenstrahlen und der Nuklearmedizin 1990;152(2):214‐9. - PubMed
    1. Wacker FK, König H. Quantitative evaluation of magnetic resonance imaging in long‐term therapy: a pilot study in patients with osteoarthritis of the knee. Acta Pharmaceutica 1993;43:253‐60.
Montrone 1985 {published data only}
    1. Montrone F, Fumagalli M, Sarzi Puttini P, Boccassini L, Santandrea S, Volpato R, et al. Double‐blind study of S‐adenosyl‐methionine versus placebo in hip and knee arthrosis. Clinical Rheumatology 1985;4(4):484‐5. - PubMed

References to studies excluded from this review

Bottiglieri 2002 {published data only}
    1. Anonymous. S‐adenosyl‐L‐methionine (SAMe): from the bench to the bedside ‐ molecular basis of a pleiotrophic molecule. S‐Adenosylmethionine (SAMe): from molecular mechanism to clinical implication: proceedings of a symposium held at the Oxygen Club of California 2001 World Congress, Santa Barbara, CA, March 7‐10, 2001. American Journal of Clinical Nutrition 2002;76:1151S‐57S. - PubMed
Caroli 1980 {published data only}
    1. Caroli A, Caroli A. Double‐blind study of SAMe (capsules) and aspirin in osteoarthrosis [Studio in doppio cieco SAMe (capsule) ‐ Aspirina nell'osteoartrosi.]. Giornale di Clinica Medica 1980;61(11):844‐57. - PubMed
Ceccato 1980 {published data only}
    1. Ceccato S, Cuginotta D, Carapezzi C, Ferretti G, Passeri M. Double‐blind trial on the therapeutic effect of SAMe and ibuprofen [Studio clinico in doppio cieco sull'effetto terapeutico della SAMe e dell'Ibuprofen nella patologia degenerativa osteoarticolare.]. Giornale di Clinica Medica 1980;61(2):148‐62. - PubMed
Conis 2003 {published data only}
    1. Conis E. Supplements. SAM‐e may help mood, bone health. Los Angeles Times ‐ Southern California Edition 2003; Vol. 27 October.
Cucinotta 1980 {published data only}
    1. Cucinotta D, Mancini M, Ceccato S, Castino E, Cucinotta D, Mancini M, et al. Controlled clinical study of SAMe (S‐adenosylmethionine) administered orally in degenerative osteoarticular pathology [Studio clinico controllato sull'attività della SAMe somministrata per via orale nella patologia degenerativa osteo‐articolare ]. Giornale di Clinica Medica 1980;61(7):553‐66. - PubMed
Fagan 2002 {published data only}
    1. Fagan EB, Latessa RA. S‐adenosylmethionine (SAMe) is safe and effective for osteoarthritis. Journal of Family Practice 2002;51(8):667.
Pellegrini 1980 {published data only}
    1. Pellegrini P, Pellegrini P. S‐adenosylmethionine (SAMe) in osteoarthrosis; a double‐blind crossover peroral study [La S‐Adenosil‐metionina (SAMe) nell'osteoartrosi studio in doppio cieco crossove per via orale.]. Giornale di Clinica Medica 1980;61(8):616‐27. - PubMed
Polli 1975 {published data only}
    1. Polli E, Cortellaro M, Parrini L, Tessari L, Cherie Ligniere G, Polli E, et al. Pharmacological and clinical aspects of S‐adenosylmethionine (SAMe) in primary degenerative arthropathy (osteoarthrosis) [Aspetti farmacologici e clinici della solfo‐adenosil‐metionina (SAMe) nella artropatia degenerativa primaria (osteoartrosi)]. Minerva Medica 1975;66:4443‐59. - PubMed
Schardt 2003 {published data only}
    1. Schardt D. SAM‐e so‐so. Nutrition Action Health Letter 2001;28:10‐11.
Schoenhals 2005 {published data only}
    1. Schoenhals K. Wellness. Supplements and functional food: SAMe I am: amino acid metabolite offers more than a mood boost. Better Nutrition 2005;67:47‐8.

Additional references

Altman 1996
    1. Altman R, Brandt K, Hochberg M, Moskowitz R, Bellamy N, Bloch DA, et al. Design and conduct of clinical trials in patients with osteoarthritis: recommendations from a task force of the Osteoarthritis Research Society. Results from a workshop. Osteoarthritis Cartilage 1996;4(4):217‐43. - PubMed
Bellamy 1995
    1. Bellamy N. Outcome measurement in osteoarthritis clinical trials. Journal of Rheumatology 1995;22(Suppl. 43):49‐51. - PubMed
Capretto1985
    1. Capretto C, Cremona C, Canaparo L. A double‐blind controlled study of S‐adenosylmethionine (SAMe) v. ibuprofen in gonarthrosis, coxarthrosis and spondylarthrosis. Clinical Trials Journal 1985;22(1):15‐24.
Chinn 2000
    1. Chinn S. A simple method for converting an odds ratio to effect size for use in meta‐analysis. Statistics in Medicine 2000;19(22):3127‐31. - PubMed
Clegg 2006
    1. Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New England Journal of Medicine 2006;354(8):795‐808. - PubMed
Cohen 1988
    1. Cohen J. Statistical power analysis for the behavioral sciences. 2nd Edition. Hillsdale, NJ: Lawrence Earlbaum Associates, 1988.
DerSimonian 1986
    1. DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177‐88. - PubMed
di Padova 1987
    1. Padova C. S‐adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. American Journal of Medicine 1987;83(5A):60‐5. - PubMed
Dickersin 1994
    1. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994;309(6964):1286‐91. - PMC - PubMed
Domljan 1989
    1. Domljan Z, Vrhovac B, Durrigl T, Pucar I, Domljan Z, Vrhovac B, et al. A double‐blind trial of ademetionine vs naproxen in activated gonarthrosis. International Journal of Clinical Pharmacology, Therapy, & Toxicology 1989;27(7):329‐33. - PubMed
Egger 2001
    1. Egger M, Smith GD. Principles of and procedures for systematic reviews. In: Egger M, Smith GD, Altman DG editor(s). Systematic reviews in health care: meta‐analysis in context. London: BMJ Books, 2001:23‐42.
Egger 2003
    1. Egger M, Juni P, Bartlett C, Holenstein F, Sterne J. How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. Health technology assessment (Winchester, England) 2003;7(1):1‐76. - PubMed
Fetrow 2001
    1. Fetrow CW, Avila JR. Efficacy of the dietary supplement S‐adenosyl‐L‐methionine. Annals of Pharmacotherapy 2001;35(11):1414‐25. - PubMed
Glorioso 1985
    1. Glorioso S, Todesco S, Mazzi A, Marcolongo R, Giordano M, Colombo B, et al. Double‐blind multicentre study of the activity of S‐adenosylmethionine in hip and knee osteoarthritis. International Journal of Clinical Pharmacology Research 1985;5(1):39‐49. - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck‐Ytter Y, Alonso‐Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924‐6. - PMC - PubMed
Hardy 2002
    1. Hardy M, Coulter I, Morton SC, Favreau J, Venuturupalli S, Chiappelli F, et al. S‐Adenosyl‐L‐Methionine for treatment of depression, osteoarthritis, and liver disease. Evidence Report/Technology Assessment Number 64. (Prepared by Southern California Evidence‐based Practice Center under Contract No. 290‐97‐0001). AHRQ Publication No. 02‐E034 Rockville, MD: Agency for Healthcare Research and Quality. 2002, issue October:URL: http://www.ahrq.gov/clinic/tp/sametp.htm#Report (assessed 8 May 2008).
Harmand 1987
    1. Harmand MF, Vilamitjana J, Maloche E, Duphil R, Ducassou D. Effects of S‐adenosylmethionine on human articular chondrocyte differentiation. An in vitro study. American Journal of Medicine 1987;83(5A):48‐54. - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2008
    1. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.1 [updated September 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane‐handbook.org.
Jüni 2001
    1. Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 2001;323(7303):42‐6. - PMC - PubMed
Jüni 2006
    1. Jüni P, Reichenbach S, Dieppe P. Osteoarthritis: rational approach to treating the individual. Best Practice & Research. Clinical Rheumatology 2006;20(4):721‐40. - PubMed
Maccagno 1987
    1. Maccagno A, Giorgio EE, Caston OL, Sagasta CL, Maccagno A, Giorgio EE, et al. Double‐blind controlled clinical trial of oral S‐adenosylmethionine versus piroxicam in knee osteoarthritis. American Journal of Medicine 1987;83(5A):72‐7. - PubMed
Marcolongo 1985
    1. Marcolongo R, Giordano N, Colombo B, et al. Double‐blind multicenter study of the activity of S‐adenosyl‐methionine in hip and knee osteoarthritis. Current Therapeutic Research, Clinical and Experimental 1985;37(1):82‐94.
Muller‐Fassbender 1987
    1. Muller‐Fassbender H, Muller‐Fassbender H. Double‐blind clinical trial of S‐adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. American Journal of Medicine 1987;83(5A):81‐3. - PubMed
Najm 2004
    1. Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW, Najm Wadie I, et al. S‐adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double‐blind cross‐over trial. BMC Musculoskeletal Disorders 2004;5:6. - PMC - PubMed
Nüesch 2009
    1. Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Bürgi E, Scherer M, et al. The effects of the exclusion of patients from the analysis in randomised controlled trials: meta‐epidemiological study. BMJ 2009;in press:‐. - PMC - PubMed
Pham 2004
    1. Pham T, Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M, et al. OMERACT‐OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage 2004;12(5):389‐99. - PubMed
Reichenbach 2007
    1. Reichenbach S, Sterchi R, Scherer M, Trelle S, Burgi E, Burgi U, et al. Meta‐analysis: chondroitin for osteoarthritis of the knee or hip. Annals of Internal Medicine 2007;146(8):580‐90. - PubMed
RevMan 2008 [Computer program]
    1. The Nordic Cochrane Centre. The Cochrane Collaboration. Review Manager (RevMan). Version 5.0. Copenhagen: The Nordic Cochrane Centre. The Cochrane Collaboration, 2008.
Rucker 2008
    1. Rucker G, Schwarzer G, Carpenter JR, Schumacher M. Undue reliance on I2 in assessing heterogeneity may mislead. BMC Medical Research Methodology 2008;8(1):79. - PMC - PubMed
Soeken 2002
    1. Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S‐adenosylmethionine (SAMe) for osteoarthritis. Journal of Family Practice 2002;51(5):425‐30. - PubMed
Vetter 1987
    1. Vetter G, Vetter G. Double‐blind comparative clinical trial with S‐adenosylmethionine and indomethacin in the treatment of osteoarthritis. American Journal of Medicine 1987;83(5A):78‐80. - PubMed
Witte 2002
    1. Witte S, Lasek R, Victor N. Meta‐analysis of the efficacy of adenosylmethionine and oxaceprol in the treatment of osteoarthritis [Wirksamkeit von Ademetionin und Oxaceprol fur die Behandlung von Arthrosen Eine Metaanalyse]. Orthopade 2002;31(11):1058‐65. - PubMed
Wood 2008
    1. Wood L, Egger M, Gluud LL, Schulz KF, Juni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta‐epidemiological study. BMJ (Clinical Research Ed.) 2008;336(7644):601‐5. - PMC - PubMed

MeSH terms

Substances