In a study published in the New England Journal of Medicine, the popular dietary supplement combination of glucosamine plus chondroitin sulfate did not provide significant relief from osteoarthritis pain among all participants. However, a smaller subgroup of study participants with moderate-to-severe pain showed significant relief with the combined supplements.

This research was funded by the National Centre 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 (NIH). Researchers led by rheumatologist Daniel O. Clegg, of the University of Utah, School of Medicine, Salt Lake City, conducted the 4-year study known as the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) at 16 sites across the United States.

"GAIT is another example of NIH's commitment to exploring the potential of complementary and alternative medicine to prevent and treat disease in a manner that is fair, unbiased, and scientifically rigorous," said Elias A. Zerhouni, NIH director.

GAIT enrolled nearly 1,600 participants with documented osteoarthritis of the knee. Participants were randomly assigned to receive one of five treatments daily for 24 weeks: glucosamine alone (1500 mg), chondroitin sulfate alone (1200 mg), glucosamine and chondroitin sulfate combined (same doses), a placebo, or celecoxib (200 mg), informs NIH release.

Celecoxib is an FDA-approved drug for the management of osteoarthritis pain and served as a positive control for the study. (A positive control is a treatment that investigators expect participants to respond to in a predictable way; it helps validate study results.) A positive response to treatment was defined as a 20 per cent or greater reduction in pain at week 24 compared to the start of the study.

The researchers found that participants taking celecoxib experienced statistically significant pain relief (as expected) versus placebo about 70 per cent of those taking celecoxib versus 60 per cent taking placebo had a 20 per cent or greater pain reduction. For all participants, there were no significant differences between the other treatments tested and placebo. However, for participants in the moderate-to-severe pain subgroup, glucosamine combined with chondroitin sulfate provided statistically significant pain relief compared to placebo about 79 per cent in this group had a 20 per cent or greater pain reduction compared to 54 per cent for placebo. In the subgroup of participants with mild pain, glucosamine and chondroitin sulfate together or alone did not provide statistically significant relief compared to placebo.

"This rigorous, large-scale study showed that the combination of glucosamine and chondroitin sulfate appeared to help people with moderate-to-severe pain from knee osteoarthritis, but not those with mild pain. It is important to study dietary supplements with well-designed research in order to find out what works and what does not," said Stephen E. Straus, NCCAM director.

"Because of the small size of the moderate-to-severe pain subgroup, the findings in this group for glucosamine plus chondroitin sulfate should be considered preliminary and need to be confirmed in a study designed for this purpose," said Dr. Clegg, professor of medicine and chief of rheumatology at the University of Utah, School of Medicine.

On entering the study, a participant's level of pain was assessed as either mild or moderate to severe using standard pain assessment tools and scales, such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Of the 1,583 study participants, 78 per cent were in the mild pain subgroup and the other 22 per cent were in the moderate-to-severe pain subgroup.

Level of pain was evaluated at weeks 4, 8, 16, and 24 using the WOMAC scale and other tools. In addition to taking their daily study treatment, participants could take up to 4000 mg of acetaminophen daily for pain, except for the 24 hours before they were assessed by study staff. The use of acetaminophen, however, was low, overall averaging fewer than two 500 mg tablets per day. Participants could not take other non-steroidal anti-inflammatory medicines or narcotic (opioid-based) pain relievers during the study.

"More than 20 million Americans have osteoarthritis, making it a frequent cause of physical disability among adults. We are excited to support studies looking at new treatment options that could improve the symptoms and quality of life of people with osteoarthritis," ," said Stephen I. Katz, NIAMS director.

GAIT was conducted under an investigational new drug application filed with the US Food and Drug Administration. Thus, all of the products used in the study were subject to the FDA's pharmaceutical regulations and evaluated and manufactured by an FDA-licensed clinical research pharmacy center. The glucosamine and chondroitin sulfate used were tested for purity, potency, quality, and consistency among batches. Products were retested for stability throughout the study. The dosages selected were based on the prevailing doses in the scientific literature. Few side effects from any of the treatments were reported. Those reported were generally mild, such as upset stomach, and distributed evenly across the treatment groups.

"The GAIT team's goal was to assess whether glucosamine and chondroitin sulfate, which we saw our osteoarthritis patients using, provided pain relief," said Dr. Clegg.