Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials
Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systematic review and meta-analysis of randomized placebo-controlled trials was conducted to investigate the efficacy of glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered glucosamine and/or chondroitin sulfate on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and generic inverse-variance method. Heterogeneity was tested using the I2 statistic index. Treatments with glucosamine and chondroitin were found to significantly reduce pain in VAS [weighted mean difference (WMD) − 7.41 mm, 95% CI − 14.31, − 0.51, p = 0.04 and WMD − 8.35 mm, 95% CI − 11.84, − 4.85, p < 0.00001, respectively]. Their combination did not show this behavior (WMD − 0.28 mm, 95% CI − 8.87, 8.32, p = 0.95). None of the glucosamine, chondroitin or their combination had a significant positive effect on the total WOMAC index and its subscores. Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.
KeywordsGlucosamine Chondroitin sulfate Osteoarthritis WOMAC Visual analog scale Meta-analysis
English editing was performed by Dr. Sergio Lozano (member of the American Translators Association and the American Medical Writers Association).
MSM conceptualized and designed the study, carried out the statistical analyses and interpretation of data, drafted the initial manuscript, and approved the final version as submitted. ASG contributed to conception, critically reviewed the manuscript and approved the final version as submitted. FVC contributed to conception, critically reviewed the manuscript and approved the final version as submitted. CAAO contributed to conception, critically reviewed the manuscript and approved the final version as submitted. VMPM contributed to conception, critically reviewed the manuscript and approved the final version as submitted. LESM contributed to conception and study design, carried out the statistical analyses and interpretation of data, drafted the manuscript, critically revised the manuscript, and gave final approval.
Compliance with ethical standards
Conflict of interest
Authors declare that they have no conflict of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants performed by any of the authors.
Informed consent is not applicable in this meta-analysis.
- 4.Zhang W, Nuki G, Moskowitz RW et al (2010) OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil 18:476–499. https://doi.org/10.1016/j.joca.2010.01.013 CrossRefPubMedGoogle Scholar
- 9.Imagawa K, de Andrés MC, Hashimoto K et al (2011) The epigenetic effect of glucosamine and a nuclear factor-kappa B (NF-kB) inhibitor on primary human chondrocytes—implications for osteoarthritis. Biochem Biophys Res Commun 405:362–367. https://doi.org/10.1016/j.bbrc.2011.01.007 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Bruyère O, Cooper C, Pelletier JP et al (2014) An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum 44:253–263. https://doi.org/10.1016/j.semarthrit.2014.05.014 CrossRefPubMedGoogle Scholar
- 21.Roman-Blas JA, Castañeda S, Sánchez-Pernaute O et al. (2016) Chondroitin sulfate plus glucosamine sulfate shows no superiority over placebo in a randomized, double-blind, placebo-controlled clinical trial in patients with knee osteoarthritis. Arthritis Rheumatol (Hoboken, NJ). https://doi.org/10.1002/art.39819 CrossRefGoogle Scholar
- 22.Fransen M, Agaliotis M, Nairn L et al (2015) Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis 74:851–858. https://doi.org/10.1136/annrheumdis-2013-203954 CrossRefPubMedGoogle Scholar
- 23.Lugo JP, Saiyed ZM, Lane NE (2016) Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J 15:14. https://doi.org/10.1186/s12937-016-0130-8 CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Higgins J, Green S (eds) (2009) Cochrane handbook for systematic reviews of interventions, Version 5.0.2. The Cochrane Collaboration, LondonGoogle Scholar
- 26.Sutton AJ, Abrams KR, Jones DR et al (2000) Methods for meta-analysis in medical research. West Sussex, WileyGoogle Scholar
- 29.Giordano N, Fioravanti A, Papakostas P et al (2009) The efficacy and tolerability of glucosamine sulfate in the treatment of knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Curr Ther Res Clin Exp 70:185–196. https://doi.org/10.1016/j.curtheres.2009.05.004 CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Herrero-Beaumont G, Román Ivorra JA, Trabado MDC et al (2007) Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum 56:555–567. https://doi.org/10.1002/art.22371 CrossRefPubMedGoogle Scholar
- 34.Petersen SG, Beyer N, Hansen M et al (2011) Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients. Arch Phys Med Rehabil 92:1185–1193. https://doi.org/10.1016/j.apmr.2011.03.009 CrossRefPubMedGoogle Scholar
- 40.Zegels B, Crozes P, Uebelhart D et al (2013) Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4 & 6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study. Osteoarthr Cartil 21:22–27. https://doi.org/10.1016/j.joca.2012.09.017 CrossRefPubMedGoogle Scholar
- 43.Reginster J-Y, Dudler J, Blicharski T, Pavelka K (2017) Pharmaceutical-grade chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo trial (CONCEPT). Ann Rheum Dis 76:1537–1543. https://doi.org/10.1136/annrheumdis-2016-210860 CrossRefPubMedPubMedCentralGoogle Scholar
- 46.Wildi LM, Raynauld J, Martel-pelletier J et al (2011) Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis 70:982–989. https://doi.org/10.1136/ard.2010.140848 CrossRefPubMedPubMedCentralGoogle Scholar
- 47.Kahan A, Uebelhart D, De Vathaire F et al (2009) Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a 2-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 60:524–533. https://doi.org/10.1002/art.24255 CrossRefPubMedGoogle Scholar
- 50.Railhac J-J, Zaim M, Saurel A-S et al (2012) Effect of 12 months treatment with chondroitin sulfate on cartilage volume in knee osteoarthritis patients: a randomized, double-blind, placebo-controlled pilot study using MRI. Clin Rheumatol 31:1347–1357. https://doi.org/10.1007/s10067-012-2022-4 CrossRefPubMedGoogle Scholar
- 56.Hochberg MC, Martel-Pelletier J, Monfort J et al (2016) Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis 75:37–44. https://doi.org/10.1136/annrheumdis-2014-206792 CrossRefPubMedGoogle Scholar