Efficacy of glucosamine, chondroitin sulfate may depend on level of osteoarthritis pain

Most participants in GAIT study saw little relief

The popular dietary supplements glucosamine and chondroitin sulfate proved no better than a placebo in relieving osteoarthritis knee pain in most participants of a major national trial. But the study, published in the Feb. 23 issue of the New England Journal of Medicine, also showed a smaller subgroup of trial patients with moderate to severe osteoarthritis knee pain taking the combination of the two supplements experienced significant pain relief.

"For the study population as a whole, supplements were found to be ineffective," said rheumatologist Daniel O. Clegg, M.D., professor of medicine at the University of Utah School of Medicine, chief of rheumatology at the George E. Wahlen Veterans Affairs Medical Center in Salt Lake City, and principal investigator for the national trial. "An exploratory analysis suggested, however, that the combination of glucosamine and chondroitin sulfate might be effective in patients who suffer from moderate to severe osteoarthritis knee pain."

Glucosamine, an amino sugar the body produces and distributes in cartilage and other connective tissue, and chondroitin sulfate, a complex carbohydrate that helps cartilage retain water, have become popular remedies among osteoarthritis sufferers in recent decades. But evidence of the supplements' ability to control pain had been anecdotal.

The five-year, $12.5 million Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) was designed to rigorously assess the efficacy and safety of glucosamine and chondroitin sulfate, taken either separately or in combination. Nearly 1,600 patients with painful knee osteoarthritis were enrolled in the trial and randomly assigned to take placebo, celecoxib (a widely prescribed arthritis pain drug), glucosamine, chondroitin sulfate, or a combination of the two supplements for 24 weeks. Of the 1,583 study patients, 78 percent were in the mild knee pain subgroup and the remaining 22 percent were in the moderate to severe subgroup.

Celecoxib served as the study's positive control because it is an approved osteoarthritis pain drug and participants would be expected to respond in a predictable way.

For all trial patients, celecoxib proved most effective in providing significant pain relief, with a 70 percent response rate, compared to 64 percent for glucosamine and 65 percent for chondroitin sulfate. Taken in combination, the supplements provided significant relief for 66 percent of patients who receive them. The response rate in those who took placebo was 60 percent.

In participants in the mild knee pain subgroup, celecoxib proved the most effective, significantly improving pain relief for 70 percent of those who took it, compared to nearly 64 percent for glucosamine, 67 percent for chondroitin sulfate, and 63 percent for the combination of the two. Placebo produced a 62 percent response rate for people with mild pain.

"As we expected, patients who took celecoxib showed significant improvement in pain relief," Clegg said.

In patients in the moderate-to-severe knee pain subgroup, however, the combination of the two supplements appeared to be more effective than placebo, significantly reducing pain in 79 percent of those who received it. This is compared with 69 percent who took celecoxib and 54 percent who took placebo. Because only 22 percent of the trial participants were in the moderate-to-severe subgroup, this result should be considered preliminary and further study will be required to confirm these results, according to Clegg.

Conducted at 16 U.S. academic rheumatology centers, the study was funded by the National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), components of the National Institutes of Health.

Study participants were required to have both pain and X-ray evidence of osteoarthritis in their knees. They were evaluated at the beginning of the trial and at weeks four, eight, 16, and 24, with a positive treatment response defined as a 20 percent or greater decrease in knee pain compared to the start of the study.

More than 20 million Americans have osteoarthritis. Oral doses of glucosamine and chondroitin sulfate, derived from animal products, have become popular with arthritis sufferers in the past 20 or so years.

"I urge people with osteoarthritis to follow a comprehensive plan for managing their arthritis pain. Developing and maintaining a healthy lifestyle is key to the successful management of osteoarthritis--eat right, exercise regularly, lose excess weight, and consider the use of medications based on your degree of pain," Clegg said.

In a second part of the study, Clegg and other researchers will track whether taking glucosamine and chondroitin sulfate alone and in combination affects progression of knee osteoarthritis. All participants in the second part of the study had a knee X-ray at the beginning of the trial and will be imaged again at years one and two. X-rays will be compared and evaluated to assess whether these supplements affect progression of osteoarthritis. Results of the second part of the study are expected in about a year.

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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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