Glucosamine and Chondroitin

Most brands of glucosamine are manufactured from chitin which is a naturally occurring polymer found in the shell of some shellfish. Chemically, it is an amino monosaccharide which is synthesised from L-glutamine and glucose in the body and found in tissues such as kidneys and the liver in addition to cartilage. It is purchased in one of three chemical forms namely, sulphate, hydrochloride and N-acetyl-glucosamine (either as a tablet or liquid).

Chondroitin sulphate consists of multiple mucopolysaccharide chains and is an essential component of cartilage. Whereas glucosamine is claimed to promote the formation and repair of cartilage, chondroitin is hypothesised as promoting cartilage water retention and elasticity as it is highly electronegative. The resulting ample presence of water within chondroitin rich cartilage may guarantees that the cartilage will be elastic yet highly resistant to friction and the forces of impact.

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Some sceptics contend that when chondroitin-sulphate supplementation is taken orally, it is chemically degraded in the digestive system long before it can reach any joints, as it is a large molecule. However research has found that about 15% is absorbed whole and also that, once out of the digestive system, chondroitin makes a beeline for tissues such as the joints and lumbar discs.

The Research and Evidence
There are no studies that categorically answer the question of how glucosamine or chondroitin actually work in the body. There is no evidence of repairing existing cartilage, supplementation to the synovial fluid or provide nourishment to tissues by any method. Supporters of glucosamine and chondroitin report a reduction in pain and swelling and faster soft-tissue healing but it is unclear how this is achieved.

There is clearly some logic that if people with osteoarthritis are lacking in some component of cartilage formation then we should attempt to replace the missing components. Some researchers has hypothesised that glucosamine provides relief for osteoarthritic pain by promoting the production of proteoglycans which is a compound found to be in short supply in damaged cartilage. Others have suggested that it may block the action of certain enzymes that may be indicated with osteoarthritis. However, there is limited research evidence for either theory.

A lot of the research that has been carried out to date is flawed and it is difficult to draw conclusions from reviews of research because of varying dose sizes, inadequate sample size, poor research methodology and, in some case, conflicts of interest with manufacturers. Also because, glucosamine and chondroitin are slow-acting drugs, it can take a long time to produce any effect. However, there is no reliable to data to indicate how long 'a long time' should be.

A major 5 year study by Clegg et al of over 1500 patients with osteoarthritis of the knee was completed in 2005 (1). This was a randomised double-blind trial for patients taking

• glucosamine hydrochloride alone
• chondroitin alone
• a combination of both
• an anti-inflammatory painkiller
• a placebo

and was viewed by some as being one of the first rigorous trials of glucosamine and chondroitin.

This study found no overall benefit from taking glucosamine or only chondroitin or in combination in reduction of knee pain. However, the researchers analysed a subset of the patients whose pain prior to the trial was described as moderate to severe osteoarthritis. For these patients there was a significant improvement when a combination of chondroitin and glucosamine was used. There has also been some conjecture that glucosamine sulphate is more effective than the glucosamine hydrochloride used in the Clegg study.

More recent research published in the British Medical Journal(2) also supports this finding where the authors conclude that:
"Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged."

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Conclusion
Glucosamine (with or without chondroitin) may have some beneficial effect in reducing the pain and suffering of osteoarthritis. Whether it offers advantages over better established NSAIDs or Cox-2 inhibitors has yet to be determined. Some medical practitioners suggest that clients take glucosamine suphate in combination with chondroitin for a period of three months to see if there is any noticeable improvement. If there is no significant decrease in symptoms in this time period then there is probably no point in continuing the supplementation.

No studies has found any serious side effects from either glucosamine or chondroitin, although animal research has suggested that glucosamine may worsen insulin resistance. Also chondroitin may cause bleeding in people who have a pre-existing bleeding disorder.

In passing it should also be noted that there is a wide range of quality with products on the market as the supplementation market is not regulated to anywhere near the same standards as the pharmaceutical industry. In particular, the product quality of chondroitin products is by no means assured so read labels very carefully and consult your health care practitioner before taking supplementation.

(1) D. Clegg, D.Reda, et al , "Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis". The New Journal of Medicine. Volume 354:795-808 February 23, 2006 Number 8 .
(2) S. Wandel et al, "Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis". BMJ. 2010; 341: c4675.

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