Meta-analysis dismisses benefits of glucosamine, chondroitin

By Stephen Daniells

- Last updated on GMT

Related tags Chondroitin Glucosamine Chondroitin sulfate Osteoarthritis

Meta-analysis dismisses benefits of glucosamine, chondroitin
Glucosamine and chondroitin, two of the biggest hitters in the joint health segment, do not work for reducing joint pain or impact the narrowing of joint space, says a new meta-analysis.

Despite the apparent null effects, scientists state in the British Medical Journal​ that sufferers of osteoarthritis may continue using the supplements due to the ‘perceived’ benefit on joint health.

“Some patients, however, are convinced that these preparations are beneficial, which might be because of the natural course of osteoarthritis, regression to the mean, or the placebo effect,”​ state the reviewers, led by Prof Peter Jüni from the Institute of Social and Preventive Medicine at the University of Bern in Switzerland.

In addition, the reviewers support the safety of glucosamine and chondroitin supplements and “see no harm in having patients continue these preparations as long as they perceive a benefit and cover the costs of treatment themselves”,​ they added.

However, when it comes to paying for such supplements, Prof Juni and his co-workers are clear that consumers should shoulder the cost, and not national health services or insurance companies.

“Coverage of costs by health authorities or health insurers for these preparations and novel prescriptions to patients who have not received other treatments should be discouraged,”​ they stated.

Aging populations

As populations age, the burden of osteoarthritis is growing. Over 20 million Americans suffer from osteoarthritis, and it is reported to be second only to ischemic heart disease as a cause of work disability in men over 50. According to the Center for Disease Control, the direct and indirect costs are estimated to be approaching $90 billion. Elsewhere, the figures are equally worrying, with approximately seven million people in the UK alone are reported to have long-term health problems associated with arthritis.

The market for joint health ingredients is dominated by glucosamine – now a $2bn (€1.47bn) global blockbuster. It is most commonly blended with chondroitin so the two have become linked in the minds of many consumers.

Selective science

Professor Juni and his co-workers searched the literature for “large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head”​. Of the 58 potentially eligible studies, only 10 met the inclusion criteria. This provided the reviewers with data for 3,803 people with knee or hip osteoarthritis. All studies used doses of at least 800 mg/day of chondroitin and at least 1500 mg/day of glucosamine.

According to the results, there were no clinically relevant effects of chondroitin, glucosamine, or their combination on perceived joint pain or on joint space narrowing

“We believe it unlikely that future trials will show a clinically relevant benefit of any of the evaluated preparations,”​ wrote the researchers.

Despite such statements, any unanswered question may be answered by the ongoing Long Term Evaluation of Glucosamine Sulphate Study (LEGS). The “industry independent” ​randomised trial involved 600 patients assigned to one of four groups: chondroitin sulphate, glucosamine sulphate, glucosamine plus chondroitin, or placebo. “First results will become available at the earliest in November 2011,” ​said Prof Juni and his co-workers.

Limitations and ‘convenient exclusions’

Commenting on the meta-analysis, Daniel Fabricant, PhD, vice president of scientific and global government affairs at the Natural Products Association (NPA) said he did not think the researchers "did a complete job of reviewing all the data at hand or all of the appropriate data given the tool (Bayesian statistics) they chose to use"​.

"Bayesian statistics, when used properly are allow for the inclusion of observational study data to compare those data along side with RCTs. Bayesian analysis is not predicated on randomization, and can be used to analyze data from observational studies in exactly the same way as for randomized trials... A powerful tool for certain but without looking at all the studies its sort of like driving a corvette and never taking it out of second gear."

Dr Fabricant also said that the reviewers "would be wise to be more discreet in their description of earlier RCTs, especially those with subgroups that did show some improvement. Blanket statements about efficacy are rarely accurate, especially given trials on OA which as they authors state have been conflicting.

"So, when the authors state that more research isn’t needed in this area, that wouldn’t seem to be the most prudent conclusion given that over 20 million Americans suffer from OA in some form and have few options when it comes to relief from OA," ​he added.

Andrew Shao, PhD, senior vice president, scientific & regulatory affairs for the Council for Responsible Nutrition (CRN) told NutraIngredients-USA that the investigators “conveniently excluded a large portion of the evidence base”​ on the effects of glucosamine and chondroitin

“The majority of published studies involving glucosamine and/or chondroitin are positive,” ​said Dr Shao. “Even the GAIT trial, with a 60 percent placebo effect showed that Glucosamine and Chondroitin were effective at reducing pain in knee osteoarthritis patients with moderate-to-severe pain – and outperforming the Rx drug Celebre,”​ he added.

“Furthermore, both glucosamine and chondroitin are approved drugs for osteoarthritis in various countries in Europe. This surely would not be the case if they were ineffective.

“We also must recognize that consumers have voted with their wallets - choosing to continue to derive benefits from glucosamine and chondroitin supplements, with the category experiencing significant year over year growth over the past decade. If these were ineffective, then we would not observe this kind of growth.

“The bottom line for consumers is that overall the evidence indicates that glucosamine, chondroitin or the combination is effective for improving mobility and joint discomfort in osteoarthritis patients, while also demonstrating a strong safety profile. Consumers should continue to feel confident in choosing glucosamine and chondroitin,”​ said Dr Shao.

Source: BMJ
Published online ahead of print, doi: 10.1136/bmj.c4675
“Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis”
Authors: S. Wandel, P. Juni, B. Tendal, E. Nuesch, P.M. Villiger, N.J. Welton, S. Reichenbach, S. Trelle,

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Posted by Harry simpson,

May be the claims are to high? It is certainly of benefit in joint health. Yet it does not stand alone in the most sever cases.

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Bad Grammar

Posted by Paul Clayton,

Apologies for the last comment's illiteracy. It should have been, of course, '.. the scientific illiterates who run them.'

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Bad Science

Posted by Paul Clayton,

Medics view osteoarthritis as a relatively homogenous clinical entity, but from a biochemical perspective it is easy to see that it is in fact a heterogynous condition; cartilage economics (ie the balance between synthesis and break-down rates) can be adversely affected by depletion of any number of a range of anabolic building blocks and co-factors, and anti-catabolic factors. In some cases the critical short-fall may be glucosamine and/or manganese, in others it might be a lack of proline, hydroxyproline and vitamins C and B6, in others again it may be that flavonoid depletion is dominant. The fact that so many depletion patterns may present the same clinical picture easily explains why so many trials report benefits in sub-groups; and also why meta-analyses inevitably produce null results.

Current trial designs and analytical methods are so inappropriate that one may wonder, legitimately, what motivates some of the scientific illiterates that run them.

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