Glucosamine and chondroitin sulfate, together or alone, do not effectively slow cartilage loss in the knees of osteoarthritis patients compared to placebo, according to a National Institutes of Health (NIH)-supported study.

Researchers from the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) team report their findings in the October issue of Arthritis & Rheumatism.

The two-year study, led by the University of Utah and conducted at several sites, investigated whether glucosamine and chondroitin sulfate supplements, alone or combined, could diminish the structural damage caused by osteoarthritis (OA). However, researchers say that compared to a placebo, neither had a clinically significant effect on slowing the rate of joint space width (JSW) loss, which is the distance between the ends of joint bones, as shown by X-ray.

This study was an ancillary, or additional, trial conducted by the GAIT team with a subset of participants from the original GAIT study, which sought to determine whether these dietary supplements could treat the pain of knee OA. Results from that first study, reported in 2006, suggested that overall the combination of glucosamine and chondroitin sulfate did not provide significant relief from pain among all participants. It did note that a smaller subgroup of study participants with moderate-to-severe pain showed significant relief with the combined supplements.

In the GAIT II trial, the group taking glucosamine had the least change in JSW, followed by the groups taking chondroitin sulfate, the drug celecoxib, placebo and the combination of both dietary supplements.

Andrew Shao, PhD, vice president, scientific and regulatory affairs with the Council for Responsible Nutrition (CRN), Washington, D.C., challenged the study, citing “major limitations” that question the conclusions.

“The results of the GAIT II trial are perplexing and extremely inconsistent with an existing large body of evidence that shows a benefit from glucosamine and chondroitin supplementation,” said Dr. Shao. “The results are also inconsistent with the first arm of GAIT, as well as with a series of previously published clinical trials, which examined the same outcome—the narrowing of the space between joints—and demonstrated clear benefit.”

Researchers acknowledged several study limitations and said interpreting results was complicated because participants taking placebo had a smaller loss of cartilage, or JSW, than predicted.

“The researchers expected to see a typical JSW narrowing of approximately -0.4 mm,” said Dr. Shao, “yet the actual JSW change in the placebo group was only -0.166 mm, substantially less than what was expected. Because the placebo group did not worsen as expected, there is no basis for comparison.”

The total JSW loss over two years for each group was: 0.013 millimeters (glucosamine), 0.107 mm (chondroitin sulfate), 0.111 mm (celecoxib), 0.166 mm (placebo) and 0.194 mm (glucosamine and chondroitin sulfate).

Original GAIT patients were offered the opportunity to continue their study treatment in the ancillary trial for an additional 18 months, for a total of two years. Participants were randomly assigned 500 mg glucosamine hydrochloride three times daily, sodium chondroitin sulfate 400 mg three times daily, the combination of glucosamine and chondroitin sulfate, placebo, or celecoxib 200 mg daily. The research team enrolled 572 GAIT participants who, by X-ray evidence, showed moderate (grade 2) or severe (grade 3) OA in one or both knees. At the end of the ancillary study, the team had gathered data on 581 knees.

Dr. Shao said the small sample left the study “grossly underpowered…making it highly difficult to draw any meaningful conclusions from the results.”

The findings from both GAIT trials are in direct conflict, according to Dr. Shao. “Examining a subset of the same subjects who experienced the most benefit from moderate to severe arthritis pain, GAIT II suggests that the same subgroup who experienced the most pain relief—those using the glucosamine and chondroitin combination—also experienced the most reduction in JSW. These two conclusions are inconsistent, without explanation, to say the least.”

The study also measured the percentage of participants with progression (worsening) of their OA—defined as a JSW loss of more than 0.48 mm over the two years. About 24% of participants taking the combination of glucosamine plus chondroitin sulfate showed disease progression, which was similar to placebo, but greater than either glucosamine or chondroitin sulfate alone. The researchers theorize that this may reflect interference in absorption of the two supplements when taken together.

Overall, Dr. Shao said that anecdotal reports from consumers overwhelmingly indicate that glucosamine and chondroitin or their combination are effective.  

“The bottom line is that there is a large body of evidence supporting the use of glucosamine and chondroitin as safe and effective in helping individuals who suffer from pain, discomfort and immobility due to OA,” he said. “The millions of consumers who use glucosamine and chondroitin each year and experience real benefits should continue to feel confident in these products.”