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Glucosamine
Post your experienceGlucosamine has attained great popularity as a nutritional supplement, primarily for osteoarthritis. There have been large industry sponsored clinical trials as well as independent studies.1 The role of glucosamine and nutritional supplements generally, in the development and progression of osteoarthritis is of interest to the medical profession, the public, manufacturers and commercial producers of supplements.2
Glucosamine occurs naturally and is one of the 'building blocks' of cartilage (made by combination of glucose and the amino acid glutamine by the enzyme glucosamine synthetase). Glycosaminoglycans and proteoglycans are larger molecules made from glucosamine which in combination with proteins (such as collagen and elastin) form the extracellular matrix and the cartilage in joints. It is proposed that a deficiency of glucosamine production by glucosamine synthetase leads to glucosamine deficiency in chondrocytes. This appealing theory suggests that safe, natural supplements may both prevent osteoarthritis and even reverse the cartilage loss of established osteoarthritis and thus reduce pain and improve function. It is also proposed that glucosamine has an anti-inflammatory action.3
In practice the evidence of efficacy is very mixed. Some large trials and reviews are a little disappointing for those attracted to this theory:
- A recent review again highlights that results from recent randomised controlled trials are variable.4
- One large meta-analysis combined with systematic quality assessment of trials of these preparations in hip and knee osteoarthritis concluded that some degree of efficacy seemed probable, although in their conclusion the authors suggest publication bias and exaggeration of benefit.5
- Another meta-analysis of randomised, placebo-controlled trials (between 1980 and 2002) showed efficacy for glucosamine both for relief of symptoms and modification of disease in knee osteoarthritis.6
- One large study sponsored by the National Institutes of Health (the Glucosamine/ Chondroitin Arthritis Intervention Trial or GAIT) has attempted to clarify the efficacy of these supplements, but further analysis and research is still needed.7,8,9 Some benefit in moderate pain and with joint swelling is possible, but not proven.10
- A review for the Cochrane Database looking at 20 studies with 2570 patients showed glucosamine to be superior to placebo for treatment of pain and functional impairment from symptomatic osteoarthritis using the Rotta preparations (a particular brand) and a particular method of assessment. However the benefit at 3 months was less than that measured in an earlier review of treatment for 6 weeks. Glucosamine was found to be as safe as placebo.11
- Knee osteoarthritis in postmenopausal women was investigated in a 3 year randomized, placebo-controlled trial evaluating the effect of glucosamine sulphate on symptoms and disease progression. This study reported for the first time a disease modifying effect (reduction in loss of joint space in the group treated with glucosamine sulphate).12
- A four centre, 6 month randomised, double-blind, placebo controlled discontinuation trial did not provide evidence of benefit from continued use of glucosamine sulphate.13
- A study of both glucosamine and chondroitin sulphate alone or in combination did not reduce pain effectively in patients with osteoarthritis of the knee although the combination might have been effective in the moderate-to-severe knee pain group.14
- Another randomised, double -blind, placebo-controlled trial (which recruited patients via the internet) showed glucosamine sulphate to be no better than placebo in treating symptoms of knee osteoarthritis.15 Another trial of 1500mg of glucosamine showed similar lack of effect.16
Osteoarthritis, particularly causing moderate- to- severe pain of the knee.7 It is ineffective for mild pain and the jury is still out on the effect on modifying disease progression. Although there are some disappointing results from trials there is also some evidence of benefit. With current evidence there is no reason to discourage patients from taking supplements. It presents a very attractive alternative to non-steroidal anti-inflammatory drugs.17 Glucosamine sulphate is usually preferred to glucosamine hydrochloride (fewer gastrointestinal side effects). Chondroitin particularly which is often added to supplements shows great variation in content.18,19
There are no contraindications (other than allergy to glucosamine20) although studies on these and toxicity are limited. In diabetes oral glucosamine supplementation is safe.21
Ideally patients should take a balanced, informed decision before embarking on any therapy. The attractions of the proposed mode of action and the disadvantages of alternatives (such as NSAIDs) may be enough to encourage people to take these supplements. However they are expensive and the quality of over the counter preparations is a cause for concern.22 Patients can be reassured that they do appear to be safe, relatively free of side effects and in many trials effective, at least in reducing moderate-to-severe pain. Dosages of 1000-1500mg are usually used.
Document references
- Biggee BA, McAlindon T; Glucosamine for osteoarthritis: part I, review of the clinical evidence.; Med Health R I. 2004 Jun;87(6):176-9. [abstract]
- McAlindon TE, Biggee BA; Nutritional factors and osteoarthritis: recent developments.; Curr Opin Rheumatol. 2005 Sep;17(5):647-52. [abstract]
- Simanek V, Kren V, Ulrichova J, et al; The efficacy of glucosamine and chondroitin sulfate in the treatment of osteoarthritis: are these saccharides drugs or nutraceuticals?; Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005 Jun;149(1):51-6. [abstract]
- Towheed TE, Anastassiades T; Glucosamine therapy for osteoarthritis: an update. J Rheumatol. 2007 Sep;34(9):1787-90.
- McAlindon TE, LaValley MP, Gulin JP, et al; Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis.; JAMA. 2000 Mar 15;283(11):1469-75. [abstract]
- Richy F, Bruyere O, Ethgen O, et al; Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis.; Arch Intern Med. 2003 Jul 14;163(13):1514-22. [abstract]
- Distler J, Anguelouch A; Evidence-based practice: Review of clinical evidence on the efficacy of glucosamine and chondroitin in the treatment of osteoarthritis.; J Am Acad Nurse Pract. 2006 Oct;18(10):487-93. [abstract]
- No authors listed; The NIH Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT). J Pain Palliat Care Pharmacother. 2008;22(1):39-43. [abstract]
- Sawitzke AD, Shi H, Finco MF, et al; The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum. 2008 Oct;58(10):3183-91. [abstract]
- Hochberg MC, Clegg DO; Potential effects of chondroitin sulfate on joint swelling: a GAIT report. Osteoarthritis Cartilage. 2008;16 Suppl 3:S22-4. Epub 2008 Sep 2. [abstract]
- Towheed TE, Maxwell L, Anastassiades TP, et al; Glucosamine therapy for treating osteoarthritis.; Cochrane Database Syst Rev. 2005 Apr 18;(2):CD002946. [abstract]
- Bruyere O, Pavelka K, Rovati LC, et al; Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies.; Menopause. 2004 Mar-Apr;11(2):138-43. [abstract]
- Cibere J, Kopec JA, Thorne A, et al; Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis.; Arthritis Rheum. 2004 Oct 15;51(5):738-45. [abstract]
- 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 Feb 23;354(8):795-808. [abstract]
- McAlindon T, Formica M, LaValley M, et al; Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial.; Am J Med. 2004 Nov 1;117(9):643-9. [abstract]
- Rindone JP, Hiller D, Collacott E, et al; Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee.; West J Med. 2000 Feb;172(2):91-4. [abstract]
- de los Reyes GC, Koda RT, Lien EJ; Glucosamine and chondroitin sulfates in the treatment of osteoarthritis: a survey.; Prog Drug Res. 2000;55:81-103. [abstract]
- Ebube NK, Mark W, Hahm H; Preformulation studies and characterization of proposed chondroprotective agents: glucosamine HCl and chondroitin sulfate.; Pharm Dev Technol. 2002 Nov;7(4):457-69. [abstract]
- Foot M, Mulholland M; Classification of chondroitin sulfate A, chondroitin sulfate C, glucosamine hydrochloride and glucosamine 6 sulfate using chemometric techniques.; J Pharm Biomed Anal. 2005 Jul 1;38(3):397-407. [abstract]
- No authors listed; Glucosamine allergy.; Prescrire Int. 2006 Aug;15(84):139.
- Scroggie DA, Albright A, Harris MD; The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial.; Arch Intern Med. 2003 Jul 14;163(13):1587-90. [abstract]
- Reginster JY, Bruyere O, Fraikin G, et al; Current concepts in the therapeutic management of osteoarthritis with glucosamine.; Bull Hosp Jt Dis. 2005;63(1-2):31-6. [abstract]
Document ID: 1168
Document Version: 3
Document Reference: bgp25348
Last Updated: 16 Mar 2009
Planned Review: 16 Mar 2011
The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.
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