Glucosamine

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.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.