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• Can glucosamine work in osteoarthritis? And chondroitin sulphate?
  Bernard G Bannwarth
  Published on: 17 October 2005

• Published on: 17 October 2005

  Can glucosamine work in osteoarthritis? And chondroitin sulphate?

  • Bernard G Bannwarth, MD

  Dear Editor,

  Methodological flaws of numerous positive industry-sponsored placebo-controlled clinical trials along with possible publication bias[1] raised the question of whether orally administered glucosamine therapy does work in osteoarthritis (OA)[2]. Scepticism increased after more recent independent investigations failed to demonstrate efficacy[3-6]. In light of the study by Biggee and colleagues[7] which sho...

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  Dear Editor,

  Methodological flaws of numerous positive industry-sponsored placebo-controlled clinical trials along with possible publication bias[1] raised the question of whether orally administered glucosamine therapy does work in osteoarthritis (OA)[2]. Scepticism increased after more recent independent investigations failed to demonstrate efficacy[3-6]. In light of the study by Biggee and colleagues[7] which showed that insignificant, trace amounts of glucosamine entered human serum after ingestion of a standard oral dose of glucosamine sulphate (1500 mg), I feel the actual issue is presently: “Can oral glucosamine really work in OA?”

  Of note, similar concerns may be raised about chondroitin sulphate (CS). Volpi assessed the bioavailability of CS extracted from bovine[8] and shark[9] cartilage, the major sources of CS preparations used for the treatment of OA. Twenty healthy volunteers were given a single oral dose of 4g CS, and percentage increase and significance with respect to basal (endogeneous CS) value were calculated in both studies. As such, oral intake of bovine origin CS resulted in a significant increase in CS plasma concentrations from the 2nd to the 6th hour. Although CS plasma levels increased by more than 200% at 2 and 4 hours after CS administration, the maximum measured plasma concentration (Cmax) was low, ranging from 5.2 to 23.0 microg/ml (mean ± SD: 12.7 ± 4.7 microg/ml).[8] After oral administration of ichthyic CS, the increase in CS plasma levels was significant between the 4th and the 16th hour. However, the mean Cmax was as low as 4.87 ± 2.05 microg/ml (range: 1.5 to 9.7 microg/ml).[9] It should be stressed that the dose of CS administered to these subjects was far above the standard doses of CS. In France, for example, CS of bovine origin has been approved as a prescription drug for OA and its recommended dosage is 400 mg three times daily. Accordingly, the CS plasma concentrations obtained in vivo are likely much lower than those used in in vitro studies reporting that CS could exert beneficial effects on cartilage metabolism.[10]

  Finally, well designed, rigorously controlled clinical trials are needed to elucidate the actual efficacy of both glucosamine and CS. In this respect, the results of the National Institutes of Health Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) are impatiently awaited. This large placebo-controlled clinical trial tests whether glucosamine and chondroitin used separately or in combination are effective in reducing pain and improving functional ability in patients with knee osteoarthritis. Furthermore, GAIT includes a sub-study that will assess whether glucosamine and chondroitin could alter the progression of knee osteoarthritis.

  B Bannwarth

  Department of Rheumatology Pellegrin Hospital, and Division of Therapeutics
  Victor Segalen University
  33076 Bordeaux
  France
  bernard.bannwarth@u-bordeaux2.fr

  References:

  1. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis. A systematic quality assessment and meta-analysis. JAMA 2000;283:1469-75.

  2. Chard J, Dieppe P. Glucosamine for osteoarthritis: magic, hype, or confusion? BMJ 2001;322:1439-40.

  3. Rindone JP, Hiller D, Collacott E, Nordhaugen N, Arriola G. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med 2000;172:91-4.

  4. Cibere J, Esdaile JM, Thorne A, Singer J, Kopec JA, Canvin J, et al. Multicenter randomized double-blind placebo-controlled glucosamine discontinuation trial in osteoarthritis. Arthritis Rheum 2002;46(suppl):S576.

  5. Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology (Oxford) 2002;41:279-84.

  6. McAlindon T, Formica M, LaValley M, Lehmer M, Kabbara K. Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med 2004;117:643-9.

  7. Biggee BA, Blin CM, McAlindon TE, Nuite M, Silbert JE. Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability of peripheral effectiveness. Ann Rheum Dis 2005 Aug 3 ; [Epub ahead of print].

  8. Volpi N. Oral bioavailability of chondroitin sulfate (Condrosulf®) and its constituents in healthy male volunteers. Osteoarthritis Cartilage 2002;10:768-77.

  9. Volpi N. Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers. Osteoarthritis Cartilage 2003;11:433-41.

  10. Chan PS, Caron JP, Rosa GJM. Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E2 in articular cartilage explants. Osteoarthritis Cartilage 2005;13:387- 94.

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  Conflict of Interest:
  None declared.

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