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SOME elderly folks are refusing to throw out the glucosamine pills they pop for their aching joints.
 A recent news report tells of a Swiss study just out in the British Medical Journal that reviewed 10 previously published trials covering 3,803 arthritis patients. The review concluded that glucosamine offers “no clinically relevant effect” in terms of either pain relief or improving joint structure.
Glucosamine is popular with people afflicted with osteoarthritis, a slow and painful destruction of the joints. The cause is a degeneration of the cartilage that covers and cushions the bone ends that form our joints. As that cartilage degenerates, these bone ends become exposed so that they grind against each other uncushioned.
Especially when the condition afflicts weight bearing joints – such as in the hips or knees – the pain can seriously limit one’s daily activities. The elderly patient then becomes homebound and often depressed as a result.
Therapy is usually limited to aspirin like painkillers that may cause gastrointestinal bleeding. Although doctors feel little can be done to reverse the cartilage degeneration, folk wisdom has it that glucosamine can repair the cartilage.
Largely found within joint cartilage, glucosamine is synthesised in the body in tiny amounts only. As it is not found in our food, daily supplements seem reasonable in osteoarthritis. (It is made from chitin derived from seashells.)
Since it has been studied intensively, much is known about how it works at the cellular level and how it behaves in the human body. What remains unsettled is its clinical efficacy. One approach is to resort to Cochrane Reviews, a database of systematic reviews and meta-analyses of good published clinical trials.
These reviews are done by 27,000 volunteers in more than 90 countries. (Unfortunately, this database is embedded within the subscription-based Cochrane Library, so it is not widely used.)
A Cochrane Review carried out in 1999 which covered 16 good studies – but all of short duration (24 weeks only) – concluded that glucosamine was safe and effective in treating osteoarthritis in the short term.
In 2005, an updated Cochrane Review concluded that a particular preparation – glucosamine hydrochloride – was ineffective, a fact already noted in many studies.
However, glucosamine sulphate – especially the formulation from a particular manufacturer – was suspiciously significantly more effective than placebos in reducing joint pain and improving joint function in osteoarthritis.
(In most countries, glucosamine is not a prescription drug, so its manufacture is not regulated. As a result, it is sold in various forms such as glucosamine sulphate, glucosamine hydrochloride and N-acetyl glucosamine.)
To answer the question once and for all, the US National Institutes of Health (NIH) carried out a large, two-year study (not financed by industry) at nine centres. Last month, results from the randomised double-blind controlled trial were published in the Annals of Rheumatic Diseases.
The study showed that glucosamine hydrochloride and another supplement called chondroitin as well as both in combination were no more effective than either celecoxib (a painkiller) or a placebo.
However, the NIH study should have used glucosamine sulphate instead, given that the 2005 Cochrane Review had already demonstrated glucosamine hydrochloride’s lack of efficacy.
In 2007, Boston University scientists carried out a review of the best studies to be found in the Cochrane Library itself.
In their paper published in Arthritis & Rheumatism, those studies that were linked to industry were clearly identified.
Overall, glucosamine was reported to be three to 11 times more efficacious in industry-funded studies than non-industry funded ones. Still, glucosamine hydrochloride was shown to be inefficacious in all studies, regardless of funding.
By contrast, glucosamine sulphate was shown to be inefficacious in non-industry funded studies but extremely effective in industry-funded ones. Moreover, this was especially evident when the manufacturer named in the 2005 Cochrane Review was involved. The review concluded that independent studies found glucosamine sulphate to also have no effect. However, there were too few of such studies for statistical confirmation.
Overall, older glucosamine studies tend to be more positive, perhaps because of publication bias by industry-funded or industry-affiliated authors. More recent studies tend to be less positive, perhaps because most journals now require the public registration of any clinical trial before it ever commences. As such, authors
now cannot choose to publish just the positive findings while sweeping negative ones under the carpet.
If positive results only are published, the clinical benefit is only apparent, not real. If such studies are pooled together in a meta-analysis review, that apparent though not real effect is magnified even further. Thus one must be very careful when pooling newer studies with older ones.
Overall, glucosamine hydrochloride is ineffective in treating osteoarthritis. While glucosamine sulphate appears effective in some pooled studies, there is little reason to suspect that it behaves in our bodies in any significantly different way than the hydrochloride salt.
However, glucosamine has never been noted in any study to have the dangerous side effects associated with painkillers. As it is likely to be just a harmless placebo that gives some patients who are in pain hope, there seems no need to stop popping it.
But I repeat: There is no evidence to suggest that glucosamine in all its various forms does the slightest good.
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