Rheumatology International

, Volume 38, Issue 8, pp 1413–1428 | Cite as

Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials

  • Mario Simental-Mendía
  • Adriana Sánchez-García
  • Félix Vilchez-Cavazos
  • Carlos A. Acosta-Olivo
  • Víctor M. Peña-Martínez
  • Luis E. Simental-MendíaEmail author
Systematic Review


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.


Glucosamine 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).

Author contributions

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

Informed consent is not applicable in this meta-analysis.


  1. 1.
    Nelson AE (2018) Osteoarthritis year in review 2017: clinical. Osteoarthr Cartil 26:319–325. CrossRefPubMedGoogle Scholar
  2. 2.
    Yan M, Zhang J, Yang H, Sun Y (2018) The role of leptin in osteoarthritis. Medicine (Baltimore) 97:e0257. CrossRefGoogle Scholar
  3. 3.
    Frasca D, Blomberg BB, Paganelli R (2017) Aging, obesity, and inflammatory age-related diseases. Front Immunol 8:1745. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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. CrossRefPubMedGoogle Scholar
  5. 5.
    Kalunian KC (2016) Current advances in therapies for osteoarthritis. Curr Opin Rheumatol 28:246–250. CrossRefPubMedGoogle Scholar
  6. 6.
    Sherman AL, Ojeda-Correal G, Mena J (2012) Use of glucosamine and chondroitin in persons with osteoarthritis. PM&R 4:S110–S116. CrossRefGoogle Scholar
  7. 7.
    Largo R, Alvarez-Soria MA, Diez-Ortego I et al (2003) Glucosamine inhibits IL-1beta-induced NFκB activation in human osteoarthritic chondrocytes. Osteoarthr Cartil 11:290–298CrossRefGoogle Scholar
  8. 8.
    Towheed T, Maxwell L, Anastassiades TP et al (2009) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. CrossRefGoogle Scholar
  9. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Chan PS, Caron JP, Orth MW (2006) Short-term gene expression changes in cartilage explants stimulated with interleukin beta plus glucosamine and chondroitin sulfate. J Rheumatol 33:1329–1340. CrossRefPubMedGoogle Scholar
  11. 11.
    Dalirfardouei R, Karimi G, Jamialahmadi K (2016) Molecular mechanisms and biomedical applications of glucosamine as a potential multifunctional therapeutic agent. Life Sci 152:21–29. CrossRefPubMedGoogle Scholar
  12. 12.
    Jawed H, Anjum S, Awan SI, Simjee SU (2011) Anti-arthritic effect of GN1, a novel synthetic analog of glucosamine, in the collagen-induced arthritis model in rats. Inflamm Res 60:1113–1120. CrossRefPubMedGoogle Scholar
  13. 13.
    Pearle AD, Warren RF, Rodeo SA (2005) Basic science of articular cartilage and osteoarthritis. Clin Sports Med 24:1–12. CrossRefPubMedGoogle Scholar
  14. 14.
    Hui JH, Chan SW, Li J et al (2007) Intra-articular delivery of chondroitin sulfate for the treatment of joint defects in rabbit model. J Mol Histol 38:483–489. CrossRefPubMedGoogle Scholar
  15. 15.
    Monfort J, Pelletier J-P, Garcia-Giralt N, Martel-Pelletier J (2008) Biochemical basis of the effect of chondroitin sulphate on osteoarthritis articular tissues. Ann Rheum Dis 67:735–740. CrossRefPubMedGoogle Scholar
  16. 16.
    Ronca F, Palmieri L, Panicucci P, Ronca G (1998) Anti-inflammatory activity of chondroitin sulfate. Osteoarthr Cartil 6(Suppl A):14–21CrossRefGoogle Scholar
  17. 17.
    Uitterlinden EJ, Jahr H, Koevoet JLM et al (2006) Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants. Osteoarthr Cartil 14:250–257. CrossRefPubMedGoogle Scholar
  18. 18.
    Henrotin Y, Marty M, Mobasheri A (2014) What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis? Maturitas 78:184–187. CrossRefPubMedGoogle Scholar
  19. 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. CrossRefPubMedGoogle Scholar
  20. 20.
    Mazie B, Hucher M, Zaı M et al (2004) Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthr Cartil 6:2113–2123. CrossRefGoogle Scholar
  21. 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). CrossRefGoogle Scholar
  22. 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. CrossRefPubMedGoogle Scholar
  23. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Higgins J, Green S (eds) (2009) Cochrane handbook for systematic reviews of interventions, Version 5.0.2. The Cochrane Collaboration, LondonGoogle Scholar
  26. 26.
    Sutton AJ, Abrams KR, Jones DR et al (2000) Methods for meta-analysis in medical research. West Sussex, WileyGoogle Scholar
  27. 27.
    Cibere J, Kopec JA, Thorne A et al (2004) Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Care Res 51:738–745. CrossRefGoogle Scholar
  28. 28.
    Frestedt JL, Walsh M, Kuskowski MA, Zenk JL (2008) A natural mineral supplement provides relief from knee osteoarthritis symptoms: a randomized controlled pilot trial. Nutr J 7:9. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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. CrossRefPubMedGoogle Scholar
  31. 31.
    Madhu K, Chanda K, Saji MJ (2013) Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: a randomized placebo-controlled trial. Inflammopharmacology 21:129–136. CrossRefPubMedGoogle Scholar
  32. 32.
    Pavelka K, MD P, Gatterova J et al (2002) Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 162:2113–2123. CrossRefPubMedGoogle Scholar
  33. 33.
    Rindone JP, Hiller D, Collacott E et al (2000) Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med 172:91–94. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 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. CrossRefPubMedGoogle Scholar
  35. 35.
    Reginster JY, Deroisy R, Rovati LC et al (2001) Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 357:251–256. CrossRefPubMedGoogle Scholar
  36. 36.
    Clegg DO, Reda DJ, Harris CL et al (2006) Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 354:795–808. CrossRefPubMedGoogle Scholar
  37. 37.
    Kwoh CK, Roemer FW, Hannon MJ et al (2014) Effect of oral glucosamine on joint structure in individuals with chronic knee pain: a randomized, placebo-controlled clinical trial. Arthritis Rheumatol 66:930–939. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    McAlindon T, Formica M, LaValley M et al (2004) Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med 117:643–649. CrossRefPubMedGoogle Scholar
  39. 39.
    Bourgeois P, Chales G, Dehais J et al (1998) Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 × 400 mg/day vs placebo. Osteoarthr Cartil 6:25–30. CrossRefPubMedGoogle Scholar
  40. 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. CrossRefPubMedGoogle Scholar
  41. 41.
    Bucsi L, Poór G (1998) Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarthr Cartil 6:31–36. CrossRefPubMedGoogle Scholar
  42. 42.
    Möller I, Pérez M, Monfort J et al (2010) Effectiveness of chondroitin sulphate in patients with concomitant knee osteoarthritis and psoriasis: a randomized, double-blind, placebo-controlled study. Osteoarthr Cartil 18:S32–S40. CrossRefPubMedGoogle Scholar
  43. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Uebelhart D (1998) Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthr Cartil 6:35–42. CrossRefGoogle Scholar
  45. 45.
    Uebelhart D, Malaise M, Marcolongo R et al (2004) Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a 1-year, randomized, double-blind, multicenter study versus placebo. Osteoarthr Cartil 12:269–276. CrossRefPubMedGoogle Scholar
  46. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 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. CrossRefPubMedGoogle Scholar
  48. 48.
    Mazières B, Combe B, Phan Van A et al (2001) Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study. J Rheumatol 28:173–181PubMedGoogle Scholar
  49. 49.
    Mazières B, Hucher M, Zaïm M, Garnero P (2007) Effect of chondroitin sulphate in symptomatic knee osteoarthritis: a multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis 66:639–645. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 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. CrossRefPubMedGoogle Scholar
  51. 51.
    Lubis AMT, Siagian C, Wonggokusuma E et al (2017) Comparison of glucosamine–chondroitin sulfate with and without methylsulfonylmethane in grade I–II knee osteoarthritis: a double blind randomized controlled trial. Acta Med Indones 49:105–111PubMedGoogle Scholar
  52. 52.
    Messier SP, Mihalko S, Loeser RF et al (2007) Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthr Cartil 15:1256–1266. CrossRefPubMedGoogle Scholar
  53. 53.
    Liu X, Machado GC, Eyles JP et al (2018) Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med 52:167–175. CrossRefPubMedGoogle Scholar
  54. 54.
    Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ (2015) Chondroitin for osteoarthritis. Cochrane database Syst Rev 1:CD005614. CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Henrotin Y, Lambert C (2013) Chondroitin and glucosamine in the management of osteoarthritis: an update. Curr Rheumatol Rep 15:361. CrossRefPubMedGoogle Scholar
  56. 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. CrossRefPubMedGoogle Scholar
  57. 57.
    Zeng C, Wei J, Lei G (2015) Is chondroitin sulfate plus glucosamine superior to placebo in the treatment of knee osteoarthritis? Ann Rheum Dis 74:e37–e37. CrossRefPubMedGoogle Scholar
  58. 58.
    Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M (2008) The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis 67(12):1716–1723. CrossRefPubMedGoogle Scholar
  59. 59.
    Henrotin Y, Mobasheri A, Marty M (2012) Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis? Arthritis Res Ther 14:201. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Du Souich P (2014) Absorption, distribution and mechanism of action of SYSADOAS. Pharmacol Ther 142:362–374. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Orthopedics and Traumatology ServiceUniversidad Autónoma de Nuevo León, University Hospital ‘‘Dr. José Eleuterio González’’MonterreyMexico
  2. 2.Endocrinology DivisionUniversidad Autónoma de Nuevo León, University Hospital ‘‘Dr. José Eleuterio González’’MonterreyMexico
  3. 3.Unidad de Investigación Biomédica, Delegación DurangoInstituto Mexicano del Seguro SocialDurangoMexico

Personalised recommendations