Skip to main content

Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis

Abstract

Introduction

A total of 177 patients with moderate-to-severe hip or knee osteoarthritis (OA) were tested over a period of 26 weeks in a two-center, two-armed, randomized, double-blind, comparison study. The aim was to see if a combination of glucosamine sulfate (1500 mg/day) and the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (group A), showed equivalence (noninferiority) or superiority as opposed to glucosamine sulfate alone (group B).

Methods

The primary therapy evaluation was performed using the Western Ontario and McMaster Universities Arthrosis index (WOMAC) score. At the end of the study, a reduction in the pain score of ≥20% was required (primary target criterion) and the quantitative difference in the WOMAC subscores pain, stiffness, and function were analyzed (secondary target criteria).

Results and Conclusion

When a minimal pain reduction of ≥20% was chosen, there was no statistically significant difference in the number of responders between the two groups (92.2% group A, 94.3% group B). A higher responder criterion (≥80% reduction in the WOMAC pain score) was chosen. Therefore, the frequency of responders showed a therapeutic and statistical superiority for the combination product of glucosamine sulfate and the omega-3 polyunsaturated fatty acids in patients who complied with the study protocol (group A 44%, group B 32%; P=0.044). OA symptoms (morning stiffness, pain in hips and knees) were reduced at the end of the study: by 48.5%–55.6% in group A and by 41.7%–55.3% in group B. The reduction was greater in group A than in group B. There was a tendency toward superiority shown in the secondary target criteria and concurrent variables. In the global safety evaluation, both products have been demonstrated to be very safe in long-term treatment over 26 weeks. To our knowledge, this is the first clinical trial in which glucosamine was given in combination with omega-3 fatty acids to patients with OA.

This is a preview of subscription content, access via your institution.

References

  1. Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003;81:646–656.

    PubMed  Google Scholar 

  2. Baker CL Jr, Ferguson CM. Future treatment of osteoarthritis. Orthopedics. 2005;28(suppl. 2):227–234.

    Google Scholar 

  3. Sarzi-Puttini P, Cimmino MA, Scarpa R, et al. Osteoarthritis: an overview of the disease and its treatment strategies. Semin Arthritis Rheum. 2005;35(suppl. 1):1–10.

    Article  CAS  PubMed  Google Scholar 

  4. Ameye LG, Chee WS. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther. 2006;8:R127.

    Article  PubMed  Google Scholar 

  5. Berenbaum F. New horizons and perspectives in the treatment of osteoarthritis. Arthritis Res Ther. 2008;10(suppl. 2):S1.

    Article  PubMed  Google Scholar 

  6. Mobasheri A, Vannucci SJ, Bondy CA, et al. Glucose transport and metabolism in chondrocytes: a key to understanding chondrogenesis, skeletal development and cartilage degradation in osteoarthritis. Histol Histopathol. 2002;17:1239–1267.

    CAS  PubMed  Google Scholar 

  7. Aigner T, Kim HA. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration. Arthritis Rheum. 2002;46:1986–1996.

    Article  CAS  PubMed  Google Scholar 

  8. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2008;CD002946.

  9. Kim JJ, Conrad HE. Effect of D-glucosamine concentration on the kinetics of mucopolysaccharide biosynthesis in cultured chick embryo vertebral cartilage. J Biol Chem. 1974;249:p3091–3097.

    Google Scholar 

  10. Owens S, Wagner P, Vangsness CT Jr. Recent advances in glucosamine and chondroitin supplementation. J Knee Surg. 2004;17:185–193.

    PubMed  Google Scholar 

  11. Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, doubleblind study. Arch Intern Med. 2002;162:2113–2123.

    Article  CAS  PubMed  Google Scholar 

  12. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357:251–256.

    Article  CAS  PubMed  Google Scholar 

  13. Förster K, Reichelt A. Gonarthrose - Aktuelle Aspekte in der Therapie mit Glucosaminsulfat (dona 200-S). Fortsch Med. 1998;116(suppl. 183):1–12.

    Google Scholar 

  14. Matheson AJ, Perry CM. Glucosamine: a review of its use in the management of osteoarthritis. Drugs Aging. 2003;20:1041–1060.

    Article  CAS  PubMed  Google Scholar 

  15. Müller-Faßbender H, Bach G. D-Glucosamine-sulfate als nebenwirkungsarme alternative zu nichtsteroidalen antirheumatika. In: Bach G, Stock K, editors. Aktuelle Rheumatologie Bayreuth-Pathologie-Labor-Untersuchung-Therapie 1989. Köln: Echo Verlags-GmbH; 1990;109–124.

    Google Scholar 

  16. Noack W, Fischer M, Forster KK, Rovati LC, Setnikar I. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994;2:51–59.

    Article  CAS  PubMed  Google Scholar 

  17. Reichelt A, Forster KK, Fischer M, Rovati LC, Setnikar I. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebo-controlled, double-blind study. Arzneimittelforschung. 1994;44:75–80.

    CAS  PubMed  Google Scholar 

  18. Poolsup N, Suthisisang C, Channark P, Kittikulsuth W. Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials. Ann Pharmacother. 2005;39:1080–1087.

    Article  CAS  PubMed  Google Scholar 

  19. Anderson JW, Nicolosi RJ, Borzelleca JF. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food Chem Toxicol. 2005;43:187–201.

    Article  CAS  PubMed  Google Scholar 

  20. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354:795–808.

    Article  CAS  PubMed  Google Scholar 

  21. Sanders TA. Marine oils: metabolic effects and role in human nutrition. Proc Nutr Soc. 1993;52:457–472.

    Article  CAS  PubMed  Google Scholar 

  22. Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006;83(suppl. 6):1505–1519.

    Google Scholar 

  23. Serhan CN, Arita M, Hong S, Gotlinger K. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids. 2004;39:1125–1132.

    Article  CAS  PubMed  Google Scholar 

  24. Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition. 2002;18:872–879.

    Article  CAS  PubMed  Google Scholar 

  25. Rennie KL, Hughes J, Lang R, Jebb SA. Nutritional management of rheumatoid arthritis: a review of the evidence. J Hum Nutr Diet. 2003;16:97–109.

    Article  CAS  PubMed  Google Scholar 

  26. Kremer JM, Jubiz W, Michalek A, et al. Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study. Ann Intern Med. 1987;106:497–503.

    CAS  PubMed  Google Scholar 

  27. van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis. 1990;49:76–80.

    Article  PubMed  Google Scholar 

  28. Galarraga B, Ho M, Youssef HM, et al. Cod liver oil (n-3 fatty acids) as a non-steroidal antiinflammatory drug sparing agent in rheumatoid arthritis. Rheumatology (Oxford). 2008;47:665–669.

    Article  CAS  Google Scholar 

  29. Hankenson KD, Watkins BA, Schoenlein IA, Allen KG, Turek JJ. Omega-3 fatty acids enhance ligament fibroblast collagen formation in association with changes in interleukin-6 production. Proc Soc Exp Biol Med. 2000;223:88–95.

    Article  CAS  PubMed  Google Scholar 

  30. European Agency for the Evaluation of Medicinal Products: Human Medicines Evaluation Unit (EMEA). Points to consider on clinical investigation of medicinal products used in the treatment of osteoarthritis. 1998;CPMP/EWP/784/97:1–7. Available at: www.emea.europa.eu/pdfs/human/ewp/078497en.pdf. Accessed August 4, 2009.

    Google Scholar 

  31. Maroon JC, Bost JW. Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol. 2006;65:326–331.

    Article  PubMed  Google Scholar 

  32. Stucki G, Meier D, Stucki S, et al. [Evaluation of a German version of WOMAC (Western Ontario and McMaster Universities) Arthrosis Index]. Z Rheumatol. 1996;55:40–49.

    CAS  PubMed  Google Scholar 

  33. MacLean CH, Mojica WA, Morton SC, et al. Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Evid Rep Technol Assess (Summ). 2004;(89):1–4.

    Google Scholar 

  34. Wang Y, Wluka AE, Hodge AM, et al. Effect of fatty acids on bone marrow lesions and knee cartilage in healthy, middle-aged subjects without clinical knee osteoarthritis. Osteoarthritis Cartilage. 2008;16:579–583.

    Article  CAS  PubMed  Google Scholar 

  35. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469–1475.

    Article  CAS  PubMed  Google Scholar 

  36. Vlad SC, LaValley MP, McAlindon TE, Felson DT. Glucosamine for pain in osteoarthritis: why do trial results differ? Arthritis Rheum. 2007;56:2267–2277.

    Article  CAS  PubMed  Google Scholar 

  37. Reginster JY. The efficacy of glucosamine sulfate in osteoarthritis: financial and nonfinancial conflict of interest. Arthritis Rheum. 2007;56:2105–2110.

    Article  CAS  PubMed  Google Scholar 

  38. Bruyere O, Reginster JY. Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis. Drugs Aging. 2007;24:573–580.

    Article  CAS  PubMed  Google Scholar 

  39. Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum. 2007;56:555–567.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joerg Gruenwald.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gruenwald, J., Petzold, E., Busch, R. et al. Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis. Adv Therapy 26, 858 (2009). https://doi.org/10.1007/s12325-009-0060-3

Download citation

  • Received:

  • Published:

  • DOI: https://doi.org/10.1007/s12325-009-0060-3

Keywords

  • comparison study
  • docosahexaenoic acid
  • double-blind
  • eicosapentaenoic acid
  • glucosamine sulfate
  • omega-3 fatty acids
  • osteoarthritis
  • randomized
  • WOMAC