Conflicting data on glucosamine, chondroitin sulfate concerns public, physicians

Expert suggests combined treatment works, recommends three-month trial for patients.

By Tina DiMarcantonio
ORTHOPEDICS TODAY 2006; 26:24
August 2006

Patients and physicians alike are struggling to sift through the often-conflicting information on glucosamine and chondroitin sulfate use for relieving osteoarthritis pain.

The most significant contribution to this confusion: A National Institutes of Health (NIH)-funded study – known as the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) – which was presented at the 2005 American College of Rheumatology (ACR) meeting.

In the study abstract, researchers concluded that glucosamine and chondroitin sulfate effectively treat moderate-to-severe osteoarthritis knee pain, according to David S. Hungerford, MD, orthopedic surgeon at The Johns Hopkins University in Baltimore.


David S. Hungerford

“From the podium, however … [the study’s principal author, Daniel O. Clegg, MD] concluded, ‘Glucosamine and chondroitin sulfate are no better than placebo,’” Hungerford told colleagues at the 7th Annual Current Concepts in Joint Replacement Spring 2006 Meeting.

The contradictions did not stop there. “This has led to a lot of controversy in the lay public, with articles in the New York Times saying that the GAIT study shows no significant effect of nutraceuticals, and then Clegg appearing in a post-ACR meeting saying that there was some significance. So, it’s confusing,” Hungerford said.

Hungerford said that the GAIT study contradictions might be related to a variation in evaluation methods, including the WOMAC Osteoarthritis Index and the Outcome Measures in Rheumatology (OMERACT) score.

The GAIT study, a five-arm multicenter study beginning in 1999, enrolled roughly 1,500 patients. Researchers randomized patients to receive glucosamine alone, chondroitin sulfate alone, combined glucosamine and chondroitin sulfate, Celebrex, or placebo.
Among patients with a WOMAC pain score of 125 mm to 300 mm, those taking Celebrex reported the only statistically significant improvement (P=.04).



“But with a WOMAC pain score [of 301 mm to 400 mm], the combination of glucosamine and chondroitin sulfate (79.2%) is statistically significant (P=.002), and Celebrex, interestingly enough, is not statistically significant in this group,” Hungerford said.

No response in mild pain group
Although the researchers found that glucosamine and chondroitin sulfate effectively treated moderate-to-severe osteoarthritis, they found no response in patients with mild pain because of a “floor effect” that limited the ability to detect a response, he said.


In patients with a low WOMAC pain stratum, celecoxib shows significant improvement, while glucosamine and chondroitin sulfate do not. But the roles are reversed on the higher pain scale.

Source: Hungerford DS

Overall, the researchers said there was a significant improvement with Celebrex and not for the combined glucosamine and chondroitin sulfate. However, the researchers enrolled significantly fewer patients in the moderate-to-severe group compared to the mild group, Hungerford said.

He also found that the WOMAC score might not be sensitive enough to detect all changes and requires a 20% improvement for a positive response.

“If you look at the OMERACT … [there] was [a] statistically significant difference for both Celebrex and glucosamine and chondroitin [sulfate] for the group as a whole,” Hungerford said.

Three-month trial recommended
Hungerford has recommended the combined therapy in his practice for 10 years and believes that a three-month trial is the best approach. “If a patient responds, then he or she should continue. If the patient doesn’t respond, you don’t continue,” he said.

No study has shown negative side effects with glucosamine and chondroitin sulfate, such as those found with some NSAIDs like Vioxx, he said. Consequently, “[the combination] is a reasonable thing to apply to your patients, and [it’s] basically risk-free.”

For more information:
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;354:795-808.
Hungerford D. Over-the-counter interventions: What a difference a decade makes. #65. Presented at the 7th Annual Current Concepts in Joint Replacement Spring 2006 Meeting. May 21-24, 2006. Las Vegas.

I found this info very interesting. I have very mild osteoarthritis myself, but my husband had more severe osteoarthritis, and my son is starting, at his relatively young age. My mother has sworn by the combination of glucosamine and chondroitin, and said it kept her going for years until she finally had to have a complete knee replacement. Of course, she is in her 80's, so I don't think that is too bad. She has had knee problems since her 30's, probably, and had been taking the glucosamine and chondroitin for probably 20 years before the surgery. So I think it really did work for her. My husband also noticed it seemed to help him.
I can see I need to start posting in this forum, too. You have some very good info, and looks like you could use the support. I usually post in the myasthenia gravis and autoimmune forums.
Hugs,

And this was after I found a very good website showing the chemistry for
glutamine/glutamate. It is on a gene website. There are many enzymes that
are involved with this amino acid...and some convert to glucosamine.
(also glutathione).

In my business...I see very devoted patients to the Glucosamine/chondritin
formulas. And others (like me) where they don't really work.

I think there is a genetic variance in how glucosamine is made in the body, depending on the integrity of the enzymes involved. In the vitamin world we have just found genetic errors in folate metabolism (25 to be exact).
So I think that people who are converting to glucosamine well, who consume glutamine containing foods, do NOT need supplements.

Those with errors in the metabolism do better on the supplements.
This is why the studies see-saw around. There is really no way at present to screen these patients for any of this at this time!

It took some doing...to find this chart....
but here it is...
http://www.genome.jp/kegg/pathway/map/map00251.html

Everytime you see a NUMBER on this chart, there is an enzyme that is
controlling that function. Even if it is overwhelming...it does illustrate how complex the system is. Most doctors and non-doctors have NO idea!