Feb. 22, 2006 -- The popular dietary supplements glucosamine and chondroitin sulfate are no better than placebo for treating knee pain in most people with osteoarthritis, according to findings from a large study funded by the National Institutes of Health.
The trial was conducted at 16 sites around the country and is the most rigorous examination of the widely-used supplements ever done, researchers say. It appears in tomorrow's issue of the New England Journal of Medicine.
Osteoarthritis patients with mild pain treated for six months with the glucosamine and chondroitin sulfate, either alone or in combination, experienced no greater pain relief than patients randomly assigned to take a placebo.
Those with moderate to severe knee pain who took a combination of the two supplements did report significantly greater pain relief than patients with the same degree of pain who took a placebo.
But this subgroup of around 20% of the total study population was too small to prove the findings, researchers say.
Millions Take the Supplements
Twenty one million Americans suffer from chronic joint pain due to osteoarthritis, and that number is expected to double within the next two decades as the population ages. The condition is caused by the breakdown and eventual loss of cartilage, the rubbery substance that serves as a cushion between the bones of the joints.
According to a 2002 survey conducted by the CDC, 5.2 million people reported using glucosamine, either alone or in combination with chondroitin, and most used the supplements for arthritis pain. Both substances, which are found naturally in the body, help make and maintain cartilage.
"Since both [glucosamine and chondroitin] are important components of cartilage, it is tempting to believe that ingestion of the agents would somehow provide beneficial help to the cartilage," researcher and rheumatologist Daniel O. Clegg, MD, said in a news conference. "However, it must be stressed that there is very little understanding of any potential biologic action of either of these agents in the treatment of osteoarthritis."
Supplements vs. Placebo
The Glucosamine/chondroitin Arthritis Intervention (GAIT) trial was designed to determine if the supplements effectively treat the pain associated with osteoarthritis of the knee.
A total of 1,583 people over the age of 40 with confirmed osteoarthritis were randomly placed into five different groups. Each group took either glucosamine, chondroitin sulfate, both the supplements, the Cox-2 anti-inflammatory pain reliever Celebrex, or a placebo.
The study endpoint was a 20% or greater reduction in pain, as determined by a standardized questionnaire, after six months of treatment.
Overall, there was no significant difference in pain reduction between the people using supplements either alone or combined or those taking placebo. There was a greater improved response in the people taking Celebrex.
In the 354 patients with moderate to severe pain, however, the supplement combination appeared to be more effective than either Celebrex or placebo. The researchers say a larger study of patients with moderate to severe pain is needed to better understand the findings.
Another important unanswered question is whether the supplements can slow progression of knee osteoarthritis. Clegg and colleagues will attempt to answer this question by following about half of the original study participants who will continue taking the treatments for two years. Results from that trial are expected in about a year.
In the meantime, Clegg says that patients who want to take the supplements should probably take them in combination for just long enough to determine if they help relieve the pain.
Although few side effects were reported in the six-month study, National Center for Complementary and Alternative Medicine director Stephen Straus, MD, says the long-term safety of the supplements is unknown.
"We've learned from past studies that much longer exposures to certain medications are needed to reveal their true safety profile," he says.
Clegg also warned that the unregulated glucosamine and chondroitin products available commercially may be very different from the supplements used in the study.
Marc C. Hochberg, MD, MPH, who heads the division of rheumatology at the University of Maryland School of Medicine, says the findings also raise interesting questions about the placebo effect.
No fewer than half of the patients in the placebo arm of the study experienced significant reductions in pain, and responses in some placebo subgroups were as high as 62%.
Hochberg says the large placebo effect shows that the mind-body connection is very important in the treatment of arthritis pain.
He adds that physicians should consider treating these patients with minimal dosages of the safest pain medications available early on, graduating to stronger doses and drugs if pain persists.