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 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 (NIH). Researchers led by rheumatologist Daniel O. Clegg, MD, 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. UAB was one of the sites for this study, with investigator Larry Moreland, MD, leading the UAB portion of the study.

"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, MD, 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). 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% 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% of those taking celecoxib versus 60% taking placebo had a 20% 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% in this group had a 20% or greater pain reduction compared to 54 percent 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," said Stephen E. Straus, MD, NCCAM Director. "It is important to study dietary supplements with well-designed research in order to find out what works and what does not."

"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% were in the mild pain subgroup and the other 22% 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," said Stephen I. Katz, MD., PhD, NIAMS Director. "We are excited to support studies looking at new treatment options that could improve the symptoms and quality of life of people with osteoarthritis."

GAIT was conducted under an Investigational New Drug application filed with the U.S. 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. "I urge people with osteoarthritis to follow a comprehensive plan for managing their arthritis pain -- eat right, exercise, lose excess weight, and talk to your physician about appropriate treatment options."

The GAIT team continues their research with a smaller study to see whether glucosamine and chondroitin sulfate can alter the progression of osteoarthritis, such as delaying the narrowing of the joint spaces. About one-half of the participants in the larger GAIT study were eligible to enroll in this ancillary study. The results are expected in about a year.