Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006; 354(8):795-808.

The use of glucosamine and chondroitin generally has little effect on symptoms of knee arthritis, according to results of a study funded by the National Institutes of Health. However, these dietary supplements seem safe and patients with moderate-to-severe pain may experience some relief with them. To determine if the agents are of benefit, members of the Glucosamine/Chondroitin Arthritis Intervention Trial group enrolled 1,583 patients with knee pain during the previous 6 months. Patients were randomly assigned to 500 mg glucosamine three times daily, celecoxib (Celebrex) 200 mg daily, or inactive placebo. In the overall group, the supplements, either alone or combined, were not distinguished from placebo in any regard, including pain, stiffness, or swelling. Only celecoxib was associated with significant pain relief. Among the 22% of patients with moderate-to-severe pain, glucosamine and chondroitin provided greater pain relief than placebo. However, the authors noted that the relatively small number of patients in this subgroup may have limited the study's power to demonstrate significant benefits.