Glucosamine is extracted from the shell of crabs, lobster and shrimps, and also marketed by Cargill is a non-animal, non-shelfish derived product. Chondroitin sulfate is extracted from animal cartilage like shark cartilage.
They are the most commonly used supplements for osteoarthritis, with estimated sales of $730m in the US in 2004.
Of the 6,000 metric tons of glucosamine consumed annually around the world, the UK makes about 10 per cent of these sales.
The $14m Glucosamine/chondroitin Arthritis Intervention Trial (GAIT), sponsored by the National Institute of Health, studied the effect of glucosamine and chondroitin sulfate supplements on 1583 people with osteoarthritis. Sixty-four per cent were women.
The participants were randomly assigned to one of five test groups: Placebo (control); glucosamine only (1500 mg daily); chondroitin sulfate only (1200 mg daily); glucosamine and chondroitin sulfate; or celecoxib (200 mg daily), a common prescription medication.
After six weeks of intervention the researchers reported in the New England Journal of Medicine (Vol. 354, pp. 795-808): "Analysis of the primary outcome measure revealed that the rate of response to glucosamine and chondroitin sulfate, either alone or in combination, was not significantly higher than the rate of the response to placebo."
However, "effects in the moderate-to severe pain stratum were more substantial" when glucosamine and chondroitin sulfate were taken in combination.
Only 348 participants were in the moderate-to severe category, but reported a decrease in pain of 25 per cent on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), compared to placebo.
When used independently, glucosamine and chondroitin sulfate were no more effective than the placebo.
It should also be noted that the prescription drug celecoxib did not perform any better than the placebo for this sub-group, despite being the 'top performer' in the mild-to-moderate symptoms category.
The authors admit that the relatively mild degree of osteoarthritis pain from the volunteers may have limited the effects of the supplements, while suggesting that the relatively small number of participants with moderate-to severe pain may also have restricted the ability to observe benefits in the glucosamine only, chondroitin sulfate only, and celecoxib groups.
Another limitation is that the study was conducted under pharmaceutical rather than dietary supplement regulations, suggesting that similar formulations may not be readily available to the general public.
Marc Hochberg from the University of Maryland School of Medicine picked up on this point in an accompanying editorial (NEJM, Vol. 354, pp. 858-860).
"It is disappointing that the GAIT investigators did not use glucosamine sulfate, which is widely available as a dietary supplement in the United States, since the results would then have provided important information that might have explained [the difference with another study]."
Industry associations have welcomed the research. Dr. Andrew Shao, vice president of scientific and regulatory affairs with the Council for Responsible Nutrition (CRN) said: "This rigorous clinical trial offers strong evidence that glucosamine and chondroitin can provide significant relief from knee pain for those who suffer the most from osteoarthritis."
Dr. C. Thomas Vangsness, Jr. from the University of California agreed that the study supported the use of the supplements.
"This study provides patients with a convenient alternative to expensive pain medications. Glucosamine and chondroitin have fewer gastrointestinal side effects than non-steroidal anti-inflammatory drugs," said Vangsness.
While the results have been welcomed by industry spokespeople, the mainstream media have 'interpreted' the results differently, and have chosen a different message for the consumer, with headlines such as, "Supplements no good for arthritis" from Irish Health, "Glucosamine, chondroitin not much help for arthritic knees" from Forbes, and "2 Top-Selling Arthritis Drugs Are Found to Be Ineffective" from the New York Times.
Hochberg, seeming to agree with the headlines, said that it was prudent to recommend against these supplements for patients with osteoarthritis, but if the patients chose to take the supplements that doctors recommend taking both glucosamine and chondroitin sulfate together since they "may have an additive effect" - statements that seem contradictory.
Interestingly, Hochberg admits to receiving money from pharmaceutical companies such as Pfizer, a fact that raises doubts about the choice of Dr. Hochberg as an 'independent' expert to comment on the study.
Approximately seven million people in the UK alone are reported to have long-term health problems associated with arthritis. Around 206 million working days were lost in the UK in 1999-2000, equal to £18 billion (€26 billion) of lost productivity.