Does glucosamine really work?

You’ll never hear a bad word about glucosamine, but here’s the lowdown on whether it works

Glucosamine is a rare example of an ‘alternative’ supplement that has gained widespread mainstream credibility among both the general public and medical practitioners. Either by itself or in combination with chondroitin, glucosamine is used commonly by older people to help relieve pain from arthritic joints, and is also often advocated by therapists for clients recovering from soft-tissue injuries, in the belief that it promotes cartilage repair.

Such has been glucosamine’s soaring popularity that in 2000, the US National Institutes for Health launched the biggest trial of the compound to date. Its headline preliminary findings were announced at the end of 2005.

What is glucosamine?

Glucosamine is an amino monosaccharide (sugar), made within the body, and found in numerous tissues including the kidneys, liver and cartilage. Most of the over-the-counter formulations are made from chitin, a natural polymer found typically in the shell of shellfish and other invertebrates. Manufacturers tend to offer three forms of glucosamine: sulphate, hydrochloride and N-acetyl-glucosamine, taken either as a tablet or liquid. Doses range from 250mg to 1,500mg.

Chondroitin sulphate is a glycosaminoglycan (like a sugar) and is an essential constituent of cartilage. The only way to obtain chondroitin as a dietary supplement is from animal cartilage. There are no reputable dietary recommendations for safe consumption levels of a daily dose of chondroitin. Over-the-counter formulations vary widely, but most contain 400mg to 600mg of chondroitin.

The existing evidence base

There are no reputable studies that can answer the question of how either glucosamine or chondroitin work in the human body. We have no evidence that they repair existing articular cartilage, supplement the synovial fluid or nourish tissues in any way. While advocates of glucosamine and chondroitin report a reduction in pain and swelling, quicker soft-tissue healing and prophylactic protection against damage to cartilage, we do not know how these compounds may do this.

While there is some evidence from both veterinary and human clinical trials that glucosamine may have a role in treating the pain of knee osteoarthritis, most of the trials fail to reach the most basic standards of research methodology. This doesn’t stop the alternative health lobby seizing on the results as proof of glucosamine’s efficacy. If you want to read some of the studies, a good starting point is the meta-analysis (research overview) performed by McAlindon in 2000(1). Three of the trials demonstrated that glucosamine performed better than placebo. However, McAlindon’s analysis highlights among the studies examples of varying doses, inadequate sample size, poor methodology, poor randomisation, conflicts of interest with manufacturers and poor patient selection. More recent trials have been published but they also suffer from flaws (2,3,4).

The US trial

The US National Institutes for Health trial, launched in 2000, was a multi-centre randomised double blind control trial, comparing:

• glucosamine sulphate alone;
• chondroitin sulphate alone;
• glucosamine and chondroitin in combination;
• celecoxib (a Cox-2 anti-inflammatory painkiller);
• a placebo.

The trial, based in the United States, recruited 1,583 participants in 16 trial centres. Patients over the age of 40 with knee osteoarthritis were eligible. All subjects participated in the main trial. This looked at pain reduction in patients suffering from knee osteoarthritis over a 24-week period. The participants were reviewed at 4, 8, 16 and 24 weeks. A subset of subjects continued taking their formulations over an 18-month period, to examine any effects in moderating the progress of their osteoarthritis.
Initial results were presented in November 2005 at the annual meeting of the American College of Rheumatology.

What the US trial found

Remember, this study was the gold standard, a randomised double blind trial on more than 1,500 patients, taking glucosamine hydrochloride or a combination of other drugs. Overall the results showed no difference in pain reduction in those patients who took a placebo, versus only glucosamine, versus only chondroitin, versus a combination of glucosamine and chondroitin.

However, the researchers analysed a second subset of patients selected from the original 1,583, who were classed as having moderate to severe osteoarthritis. These patients recorded a significant improvement when using a combination of chondroitin and glucosamine.

To complicate matters

Further confounding the issue is a European study which was also randomised and double blind, performed in Spain in 2003, which compared glucosamine sulphate, acetaminophen (Tylenol) and a placebo. This study showed a significant reduction in pain in the glucosamine group.

Why the results are different is hard to explain. The Spanish study was industry funded and did have significantly fewer participants. The Spanish researchers have claimed that what made the difference was their use of glucosamine sulphate as opposed to the glucosamine hydrochloride used in the US study. The American researchers feel that the discrepancies may be explained by higher pain thresholds and more severe pain at the starting point in the European patients.

The full results of the US study have yet to be published. However, as it stands, there is some evidence that glucosamine sulphate on its own and glucosamine hydrochloride with chondroitin may reduce the pain of knee osteoarthritis in moderate to severe cases.

We have no evidence for repairing cartilage, maintaining cartilage health, promoting joint lubrication or any of the many other claims. Can we say it is of use to athletes as a prophylactic measure to prevent cartilage damage? No. Can we say it will quicken healing? No. It feels, for all the weight (and the wait) of the five-year US trial, that we are no nearer an answer on which to base therapeutic advice to sports clients.

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; 283:1469-1475
2. Reginster JY, Deroisy R, Rovatti LC, et al ‘Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial’ Lancet 2001; 357:251-256
3. Das A, Hammad TA ‘Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis’ Osteoarthritis Cartilage 2000; 8:343-350
4. Müller-Fassbender H, Bach GL, Haase W, Rovati LC, Setnikar I ‘Glucosamine sulfate in osteoarthritis of the knee’ Osteoarthritis Cartilage 1994; 2:61-69