Despite the fact that there are over 40 clinical studies on glucosamine and chondroitin, the results of this study were highly anticipated by physicians in the US.
GAIT is a large study, it was funded by NIH (NIAMS), and is the first major clinical study to directly compare the combination of glucosamine and chondroitin head-to-head against celecoxib (Celebrex), a prescription anti-inflammatory drug FDA approved for osteoarthritis pain.
Furthermore, the criteria used were rather rigorous. A 20% change in the WOMAC scale is a significant difference in pain and function. In addition, researchers also looked to see what treatments offered subjects at least a 50% change in their WOMAC score.
Unfortunately, as we'll see below, there were problems with the study that bias to the results toward negative outcomes. In other words, even though the treatment groups might really be effective, certain problems within the study would make it appear that the treatments were not that potent.
Why GAIT Underestimated The Effects of All of the Treatments
The first thing that should jump out to everyone who reads the results of GAIT is that the prescription drug celecoxib was no better than placebo in those patients who were most severely affected by arthritis. This result is in sharp contrast to several other large studies which do indeed show some benefit to celecoxib - that's how the drug became FDA approved from the start.
Why didn't the prescription drug help those who had the most severe pain? Obviously, there was something about the study that blunted the results, not only for Celebrex, but for all of the groups.
As impressive as the data may appear in favor of the supplements, there were really many negative biases to the study that would likely decrease the results are even wash out the data:
1) Subjects who entered the study were allowed to have taken glucosamine and chondroitin in the past. Since we don't actually know how long the washout is for the supplements, or indeed if there is a washout period, this would blunt the effect during the treatment. The eight-year study on glucosamine published and presented in 2004 showed that even people who only took glucosamine alone for three years had a 75% reduction in joint replacement surgery at the end of eight years is an example of the long-term effect of the supplements.
Here's how this could wipe out the results in GAIT. if you were studies subject who had been taking glucosamine and chondroitin prior to entering the study, then you were put into one of the research groups, but say the glucosamine alone group, it's unlikely you would start to show benefit in the study when you're actually receiving less treatment then when you entered! it's possible that you noticed your pain increased during the study because you were without your usual chondroitin.
So why did the researchers even allow people who had been on the supplements in the past to enter the study? Recruitment of suitable study participants was difficult and the investigators had much trouble finding people who had not been exposed to the supplements in the past.
2) In my experience, backed by reviewing some basic science literature, it's very apparent some of the causes of secondary osteoarthritis respond much better to the supplements than those with primary OA (the subjects used in GAIT). Osteoarthritis caused from gout and pseudogout, for instance usually results in miraculous recoveries once people start taking the supplements.
3) Split dosing, three times a day for the supplements decreases the concentration in the blood and is likely not as effective as once a day dosing, which is been recommended for many years. We can't blame the investigators for this, the study was designed when the thinking was that split dosing was okay. This was before the data on the blood concentrations in pharmacokinetics was established.
4) The extremely high placebo rate obviously could result in the washout of data. Even though the supplements did better than placebo in every instance, either alone or together in combination, there was no statistical significance in the individual supplements because the placebo rate was so high. This is what the conclusion alluded to when it mentioned the "floor effect." Perhaps one of the reasons the placebo rate was so high was because a faintness of heart test was used to help weed out those study subjects who were most likely to drop out and not follow the protocol. The bad part of this methodology is it one is left with patients that are very "gung ho" and more likely to experience an Avis effect, which is a bias that subjects in a study are more likely to respond just because they are involved in a study and are being evaluated.
5) The study was first initiated in the late 1990s. Since that time, we've made significant advances in the dietary supplement intervention for arthritis. New formulations and ingredients can improve the benefits to many patients who are not helped by ordinary glucosamine and chondroitin alone.
Safety/Cost Concerns Not Well Elaborated in GAIT
Celebrex costs $2-$3 per day compared to $.50 to $1 per day for the dietary supplements glucosamine and chondroitin. Added to the cost of Celebrex however is the cost of a physician visit to write the prescription for the drug, as well as the cost of co-medication necessary to help keep the Celebrex from causing a life threatening, bleeding ulcer.
New guidelines call for all people at high risk for developing an ulcer (even those just taking low-dose aspirin as a heart protector), to also a proton pump inhibitor drug (special acid blockers such as the trade drugs: Aciphex, Nexium, Prevacid or Prilosec). The cost for proton pump inhibitors range from about $1 per day up to $4 per day. In addition, these drugs are not without their own risks and side effects.
It does not make sense to pay up to $7 per day for drugs that barely do better for only three out of every 100 people with mild pain, and don't even approach the benefit of glucosamine/chondroitin for those with moderate to severe pain
It's really going to be fun (but frustrating however) to watch the drug companies and their representatives try to spin these results into their favor. I would gladly debate anyone concerning the implications of this study at any time and any place.
What's Important to the Public?
Given the fact of the combination of supplements blew away Celebrex in those people who actually needed intervention (those in the high-pain group), it's clear that it may become malpractice to use anti-inflammatory drugs as first-line therapy unless the patient has failed six months of therapy was a good quality combination glucosamine and chondroitin product. My position hasn't changed, the data has just caught up. NSAIDs should be last-line therapy in osteoarthritis, before surgery.
Bear in mind, that the use of these dietary supplements is really only one of nine steps I detailed in The Arthritis Cure - Revised Edition. As a result, people who implement the entire program should expect results even more significant than those who just utilize the individual step of consuming glucosamine and chondroitin.
Notes to the media/health writers:
Please contact me related to your stories. I have a number of peer-reviewed articles to support my statements and I can help explain the details of the study in sight am an oversight committee member.
My contact information information is on the homepage of this site at the lower left-hand corner.
More to follow soon...
Jason Theodosakis, MD, MS, MPH, FACPM
Purpose and Results < > Main NIH Page