April, 2006

 GLUCOSAMINE AND CHONDROITIN SULFATE

Glucosamine, taken for treatment of arthritis, is one of the most popular dietary supplements. It is usually sold in the form of its sulfate salt (glucosamine sulfate). Glucosamine supplements often contain another molecule, chondroitin sulfate, as well. Claims have been made that glucosamine and chondroitin can not only relieve symptoms and fight progression of arthritis, but also reverse or cure it (a popular 1997 book promoting these supplements, The Arthritis Cure, is subtitled “The Medical Miracle That Can Halt, Reverse, and May Even Cure Osteoarthritis”).

There are complex sugar-containing molecules called proteoglycans that are found outside of cells and are particularly important in the joints. Glucosamine (or its modified form, N-acetylglucosamine) is one of the important sugars found in the proteoglycans. However, there is no need to eat glucosamine because the body normally synthesizes it from other sugars like glucose. Chondroitin sulfate is one of the types of sugar structure found in the proteoglycans. It is also made by the body and does not need to be eaten in the diet. Moreover, while glucosamine is a small molecule and can be taken up by the body, it is highly unlikely that chondroitin sulfate from a supplement could be absorbed into the body without first being broken down into small pieces. Even if some were taken up, it would then be unlikely that it would go to your joints and be useful.

Since glucosamine can be taken up and get to various cells of the body, is it possible that it could be beneficial in arthritis? One idea is that it could help cells make more proteoglycans than if they have to rely on the glucosamine that they make themselves. However, a laboratory investigation with chondrocytes (the cells that make cartilage) found that even when they were given extremely high levels of glucosamine (more than one could get by eating supplements), they did not make any more proteoglycans (Abstract). Another idea is that somehow the extra glucosamine decreases the enzymes that break down proteoglycans, so the cartilage is preserved better.

What do research studies say about the value of glucosamine and chondroitin supplements for people with arthritis? While there have been some studies indicating that these are useful, other studies have found them not to be effective. A 2005 review (Abstract) gave mostly negative conclusions. It is interesting that the studies that gave positive results were funded by manufacturers of the supplements, while negative results were obtained by independent researchers.

In Feburary, results of a major trial of glucosamine and chondroitin sulfate were published (Clegg et al. (2006) N. Engl. J. Med. 354, 795-808 (Abstract)). In this study, 1583 patients with knee osteoarthritis were given daily doses of either 1500 mg glucosamine, 1200 mg chondroitin sulfate, both glucosamine and chondroitin, 200 mg celecoxib (a nonsteroidal inti-inflammatory drug marketed under the name Celebrex), or no drug (placebo). They were followed for 24 weeks. The numbers of patients whose pain decreased by 20% over the 24 week period was measured. These were 64.0% for glucosamine, 65.4% for chondroitin sulfate, 66.6% for glucosamine plus chondroitin, 70.1% for celecoxib, and 60.1% for placebo.

The differences were not statistically significant for glucosamine, chondroitin sulfate, and glucosamine plus chondroitin vs. placebo. Thus, the study did not find evidence that these were effective in treating arthritis pain. The effect of celecoxib was significantly greater than placebo.

The data were also examined for two subgroups of the study population. For patients with mild pain, the results were similar to those for the entire population. However, for patients with moderate to severe pain, 57% of those receiving both glucosamine and chondroitin sulfate improved, compared to 38% of the placebo group, a statistically significant difference. While this suggests that the supplements may be useful for some patients, these results should be interpreted with caution. Only 22% of the study population fell into this category, and because the numbers studied were relatively small the authors concluded that these results should be considered preliminary. Analyzing subgroups of a clinical trial can sometimes give misleading results simply by chance, and it is important to confirm any such conclusions with studies designed specifically to test a particular hypothesis (in this case, that the supplements are useful for patients with moderate to severe pain).

An interesting aspect of the study is the high degree of placebo effect, with 60% of the patients reporting pain decreases despite getting no treatment. This explains why many users of glucosamine and chondroitin may feel that it is beneficial even though it may not be, and emphasizes the need for controlled studies of these and other supplements.

For further discussion of this trial, see a Press Release and Questions and Answers from the National Center for Complementary and Alternative Medicine.

In summary, the results of this new study call into question the value of glucosamine and chondroitin for many users. While it suggests that those with the greatest pain may obtain some benefit, this remains to be confirmed with other studies.

For further information, see: Barrett, S. (2006) "Glucosamine for Arthritis: The Evidence is Conflicting."

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