Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)

Review of the Feb. 23, 2006, New England Journal of Medicine (NEJM)
report on a study of Glucosamine and Chondroitin supplements for knee arthritis.

Glucosamine and chondroitin sulfate are synthesized in the body. Glucosamine, an amino sugar is believed important for cartilage formation and repair. Chondroitin sulfate is a sugar-protein substance (proteoglycan) important in cartilage elasticity. A report by NEJM on a recent research study of Glucosamine and Chondroitin suggests both dietary supplements may benefit patients with moderate to severe osteoarthritis of the knees. 

Although both Glucosamine and Chondroitin appear to relieve pain, improve joint mobility decrease inflammation, the ability of these substances to prevent or reverse osteoarthritis is still in question. Other nutritional factors that may affect osteoarthritis include mineral imbalance, protein malnutrition, bowel disorders, metabolic disorders, food allergies or sensitivities, and Non Steroidal Anti-inflammatory Drugs (NSAIDs). In this context, Glucosamine and Chondroitin may only be compensating for a greater problem of dietary, digestive or metabolic malnutrition..

John W. Cartmell, MS

Glucosamine and Chondroitin Sulfate for Knee Osteoarthritis
— Allan S. Brett, MD
Published in Journal Watch February 28, 2006

In this long-awaited Multicenter NIH-supported trial, researchers examined the dietary supplements glucosamine and chondroitin sulfate in patients with knee osteoarthritis. The trial included 1583 patients with knee pain for at least 6 months, plus radiographic evidence of knee osteoarthritis. Patients were randomized to receive placebo, glucosamine hydrochloride (500 mg 3 times daily), chondroitin sulfate (400 mg 3 times daily), both supplements, or celecoxib (200 mg daily). A response to treatment was defined as a 20% decrease in pain on a standardized scale at 24 weeks.

Overall response rates were 60%, 64%, 65%, 67%, and 70% in the placebo, glucosamine, chondroitin, glucosamine/chondroitin, and celecoxib groups, respectively.

Only the response to celecoxib (Celebrex) was statistically significant compared with placebo. In a subgroup of patients with moderate-to-severe pain (22% of participants), response rates were 54%, 66%, 61%, 79%, and 69%, respectively. Only the 79% response to combined glucosamine/chondroitin was statistically significant compared with placebo. Patients' global assessments of response to therapy were not statistically significant for any active treatment (compared with placebo) in either the mild or moderate-to-severe subgroups.

Comment: In this trial, glucosamine hydrochloride, chondroitin sulfate, or combination therapy conferred no benefit in patients with mild knee osteoarthritis. The observed benefit from combined therapy in the subgroup with moderate-to-severe symptoms is provocative and deserves further study. An editorialist outlines several caveats about this study and questions whether outcomes for glucosamine hydrochloride (used in this study) can be extrapolated to glucosamine sulfate (used in many marketed products). Another report on the effect of these supplements on radiographic progression is expected.  

“The New England Journal of Medicine” Reviews the GAIT Study: Glucosamine, Chondroitin Sulfate and the Two in Combination for Painful Knee Osteoarthritis

Excerpted from:

Barcelona, Spain February 22, 2006 -- While “The New England Journal of Medicine” concludes that there is still no resolution for the use of supplements in treating knee osteoarthritis (OA), much of the data coming out of the GAIT study suggests otherwise.

In the overall population of all patients with mild to moderate pain the results, for supplement use, while positive, were not statistically significant.

Even the researchers themselves commented that the study had a number of limitations. The high rate of response to placebo (60.1%) and the relatively mild degree of pain from OA among participants, may have limited the ability to detect the benefits of the treatments.

However, in the severe pain group the Glucosamine + Chondroitin Sulfate combination scored higher than both placebo and celecoxib, concluding that the combination of glucosamine and chondroitin sulfate is effective in treating moderate to severe pain in patients with knee OA.

Also reported in “The New England Journal of Medicine” was that treatment with chondroitin sulfate alone was associated with a significant decrease in the incidence of joint swelling and effusion.

Doctors treating patients are always concerned about addressing a number of issues. Getting the pain under control is the first step, however, dealing with all the other symptoms such as joint swelling, stiffness and function is just as important. It is a vicious cycle; joint swelling in 90% of patients is caused by joint effusion. Joint effusion is an increase of liquid inside the articular space, which produces pain and functional incapacity. According to Nicholas DiNubile, MD and orthopaedic surgeon, “It’s crucial when treating osteoarthritis to break that cycle and treat the disease. I find that joint supplements are a very effective and risk-free way of doing that and it’s good to have data that supports what I see in my clinical practice everyday.”

While this major clinical trial is not offering conclusive results, it suggests a need for more research.  Jason Theodosakis M.D. has a decade of practical use and two best selling books on the subject. According to Theodosakis, “With any medical intervention, the risk/benefit/cost considerations must also be addressed. Glucosamine/chondroitin have the best safety record of any prescription or over-the-counter oral treatment for OA. The results of the GAIT study exulted the benefits in those who actually needed the most relief and the cost of good quality (pharmaceutical grade) supplements is approximately one dollar a day, a third of the price of the most popular drug prescribed.”

The study was conducted under pharmaceutical rather than dietary supplement regulations and, as such, the supplements were held to stringent standards of pharmaceutical manufacturing practices. Bioiberica is the leading manufacturer of pharmaceutical-grade chondroitin sulfate and was selected by the NIH as the exclusive supplier of chondroitin sulfate for the GAIT study. Its CSb™Bio-Active brand of chondroitin sulfate used in the study is commercially available in the US as Cosamin®DS.

For more information, or to arrange an interview with a company spokesperson or Dr. Theodosakis or Dr.DiNubile, please contact Tamara York at ADinfinitum, 212 693 2150 Ext 314, or Leesa Raab @ 212 693 2150 Ext. 309.

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