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Glucosamine has attained great popularity as a nutritional supplement, primarily for osteoarthritis. There have been large industry-sponsored clinical trials as well as independent studies. Glucosamine is popular with patients, in part due to the encouragement of the medical profession who, when it was first marketed, advocated it as a low-risk alternative to non-steroidal anti-inflammatory drugs.
Mechanism of action
Glucosamine occurs naturally (made by combination of glucose and the amino acid glutamine by the enzyme glucosamine synthetase) and is one of the 'building blocks' of cartilage. Glycosaminoglycans and proteoglycans are larger molecules made from glucosamine in combination with proteins such as collagen and elastin. They form the extracellular matrix and the cartilage in joints.
Animal models and in vitro experiments suggest that glucosamine stimulates cartilage production and inhibits degradation by influencing chondrocyte activity. However, limited in vivo studies suggest that very little orally ingested glucosamine reaches the joint. This does not rule out an unknown mechanism of action elsewhere but leaves no clear theory to explain an effect.[2, 3]
Evidence is mixed, with most authors now agreeing that the case for a substantial effect is unproven.
A Cochrane review in 2005, updated in 2007, suggested that whilst glucosamine appeared superior to placebo for treatment of pain and functional impairment from symptomatic osteoarthritis in around 2,500 patients, the benefit at three months was less than that measured at six weeks.[2, 7]
A 2009 systematic review looked at five systematic reviews and one clinical guideline. It concluded that there was evidence for clinical impact but that more research was needed and that as none of the trial data came from the UK, caution should be exercised in applying it here.
A 2012 review concluded that evidence was at best mixed and that any symptomatic effect observed varied greatly with the preparation used and the quality of the trial.
The National Institute for Health and Care Excellence (NICE) issued guidance on osteoarthritis in 2008 and updated it in a new guideline in 2014. Both guidelines agreed that glucosamine should not be offered on the NHS as there was insufficient evidence of benefit.
NICE guidance on osteoarthritis (February 2014) recommends that doctors do not offer glucosamine on the NHS.
The NICE Clinical Knowledge Summary (CKS) of the same year refers to glucosamine as a 'commonly promoted therapy that is not specifically recommended' and recommends that patients who wish to buy it should be advised to expect only a mild-to-moderate reduction in pain. They should be advised to perform a trial of therapy with glucosamine sulfate 1500 mg once daily (as 500 mg three times a day appears to be ineffective) and that they should review the benefits after three months.
The contra-indications are shellfish allergy and allergy to glucosamine.) However, studies on these and toxicity are limited. Avoidance is advised (by the manufacturers) in pregnancy and breast-feeding. The evidence of glucosamine on glucose metabolism is equivocal and further research is needed.
The British National Formulary (BNF) also advises caution in patients with impaired glucose tolerance and recommends monitoring blood glucose concentration before treatment and periodically thereafter. In patients with a predisposition to cardiovascular disease, lipid monitoring is recommended. In well-established stable diabetes, oral glucosamine supplementation appears to be safe.However, further research is needed to confirm whether this is true in the long term for those with poorly controlled diabetes.
Common side-effects are listed as nausea, abdominal pain, flatulence, diarrhoea, constipation, drowsiness, headache and fatigue.
Glucosamine is known to enhance the anticoagulant effect of warfarin. The BNF advises avoiding concomitant use.
Further reading and references
Stuber K, Sajko S, Kristmanson K; Efficacy of glucosamine, chondroitin, and methylsulfonylmethane for spinal degenerative joint disease and degenerative disc disease: a systematic review. J Can Chiropr Assoc. 2011 Mar55(1):47-55.
Miller KL, Clegg DO; Glucosamine and chondroitin sulfate. Rheum Dis Clin North Am. 2011 Feb37(1):103-18. Epub 2010 Dec 4.
Towheed TE, Anastassiades T; Glucosamine therapy for osteoarthritis: an update. J Rheumatol. 2007 Sep34(9):1787-90.
Henrotin Y, Mobasheri A, Marty M; Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis? Arthritis Res Ther. 2012 Jan 3014(1):201. doi: 10.1186/ar3657.
Osteoarthritis: care and management in adults; NICE Clinical Guideline (February 2014)
Osteoarthritis; NICE CKS, April 2015 (UK access only)
Wu D, Huang Y, Gu Y, et al; Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials. Int J Clin Pract. 2013 Jun67(6):585-94. doi: 10.1111/ijcp.12115.
Towheed TE, Maxwell L, Anastassiades TP, et al; Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005 Apr 18(2):CD002946.
Black C, Clar C, Henderson R, et al; The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation. Health Technol Assess. 2009 Nov13(52):1-148. doi: 10.3310/hta13520.
British National Formulary (BNF); NICE Evidence Services (UK access only)
No authors listed; Glucosamine allergy Prescrire Int. 2006 Aug
Dostrovsky NR, Towheed TE, Hudson RW, et al; The effect of glucosamine on glucose metabolism in humans: a systematic review of the literature. Osteoarthritis Cartilage. 2011 Apr19(4):375-80. Epub 2011 Jan 18.
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 14163(13):1587-90.
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