Glucosamine and Chondroitin Sulfate for Treatment of OA
Source: McAlindon TE, et al. JAMA 2000;283:1469-1475.
Osteoarthritis (oa) is a major public health problem and treatment with nonsteroidal anti-inflammatories is associated with frequent adverse effects. Since, as McAlindon and colleagues state, glucosamine and chondroitin sulfate are relatively safe preparations, they will have great use in the treatment of OA if they are effective.
McAlindon et al searched for clinical trials in Medline (June 1966-June 1999) and several other sources and contacted study authors and manufacturers of glucosamine and chondroitin. Studies were included if they were published or unpublished double-blind, randomized, placebo-controlled trials of four or more weeks duration that tested for knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis.
The overall quality score was not significantly different from the mean quality scores of other peer-reviewed journals. Only two studies reviewed reported intent-to-treat analysis. Most were supported by a manufacturer. The aggregated effect sizes were significant at the 95% confidence levels: -0.44 for glucosamine and 0.78 for chondroitin. The effects were diminished when only high-quality or large trials were considered.
McAlindon et al conclude that the glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects but quality issues and likely publication bias suggest these effects were exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations.
Comment by Ralph R. Hall, MD, FACP
Physicians will welcome therapy for OA that is effective and safe. There are, however, several barriers to the use of glucosamine and chondroitin.
The editorial accompanying this meta-analysis of studies evaluating the use of glucosamine and chondroitin is a short and excellent text on the use of meta-analysis and the bias involved when the studies are supported by manufacturers.1 Both the editorial and several letters to the editor in the same issue of JAMA note that the quality of the studies supporting the use of pharmaceuticals and supplements that are, in turn, supported by the manufacturer are peer reviewed and usually of good quality. Bias is introduced because the manufacturers fail to report negative studies.
More to the point, however, and not mentioned in any of the articles cited, is the possibility that the product may not contain sufficient amounts, or any, of the product listed on the label. Since there is no oversite by the FDA, the products are not taken to task by the FDA unless there is an event that clearly demonstrates that the product has taken a life or is dangerous for some other reason.
A relatively new organization has undertaken the task of analyzing many of the supplements and publishes their results on the Internet. Its recent review of glucosamine and chondroitin is of special interest.2 They tested 25 brands of glucosamine, chondroitin, and combined glucosamine/chondroitin products. The products were tested to determine if they possessed the labeled amounts claimed.
"Overall, nearly one-third of the products did not pass testing. Among glucosamine/chondroitin combination products; however, almost half (6 out of 13) did not pass—all due to low chondroitin levels. Similarly, the two chondroitin-only products tested did not pass. In contrast, all 10 of the glucosamine-only products passed testing."
One explanation given by the testers is that chondroitin is much more expensive than glucosamine; therefore, the manufacturers do not include adequate amounts in their preparations.
An additional concern has recently been brought to our attention. This is particularly important since there have to date not been long-term studies that establish the safety of these two products. Glucosamine given over a 12-week period was associated with increasing insulin resistance.3 This study had a small number of patients but it does raise concerns.
A review of the methods and purpose of www.consumerlabs.com is reassuring. The company appears to be reputable, have capable scientists and serve as an important source of information. It supplies information about the collection of products, where the products have been tested, and the testing methods. I urge you to check this Web site. It is a valuable source of information for both you and your patient.
A major thrust, however, should be for us all to encourage the organizations to which we belong, to get Congress to pass laws mandating that the FDA be given more oversight authority for the labeling and the safety of these products. Not only are there safety and efficacy concerns but, with the attention given to cost effectiveness, the millions of wasted dollars spent for ineffective supplements is an outrage.
1. Towheed TE, Anastassiades TP. JAMA 2000;283: 1483-1484.
3. Almada AL, et al. FASEB J 2000;14(4):A750.
Dr. Hall is Emeritus Professor of Medicine, University of Missouri-Kansas City School of Medicine.