Yes. Amy Pickens, MPAS, PA-C, says the over-the-counter supplement is a safe treatment option within the armamentarium of modalities for osteoarthritis of the knee. No, Blaine Carmichael, PA-C, says the literature and the general makeup of a glucosamine/chondroitin supplement makes it a less than viable treatment option for osteoarthritis of the knee.

Yes. This author says the over-the-counter supplement is a safe treatment option within the armamentarium of modalities for osteoarthritis of the knee.

By Amy Pickens, MPAS, PA-C

Glucosamine and chondroitin sulfate are relatively safe and inexpensive, and can be helpful in treating painful joints. It makes sense that the supplements are useful in treating symptoms associated with osteoarthritis (OA) of the knee.
The combination dietary supplement is often praised and vilified in the same sentence often by the same clinicians who recommend its use or utilize it themselves. Clinicians take both sides of the debate while recommending the product’s use or utilizing it themselves. Largely unregulated, many clinicians and many patients are asking for information regarding the effectiveness of glucosamine/chondroitin for the treatment of OA.
The likelihood of joint problems is a reality for all of us as we get older. The old adage (“Would you prescribe this for a family member?”) rings true when recommending any treatment available to our patients.


Much of the literature reports that glucosamine and chondroitin is ineffective for Osteoarthritis. Still, even authors of the oft-discussed GAIT study on this topic concede there were limitations of their study despite the many parameters they considered. Perhaps most important is that the authors noted “more substantial” results with the combination of glucosamine and chondroitin among patients with moderate to severe disease. However, this was a smaller subset of patients in comparison to the thousands of patients screened and the 1,583 patients who were actually involved with the study.1


Bear in mind that other studies that have demonstrated the effectiveness of glucosamine and chondroitin were criticized for the small number of enrolled patients and their relatively lower reported knee pain levels.


The National Institutes of Health has a credible and comprehensive information page concerning glucosamine and chondroitin. Despite confirming that the actual formulation used in the GAIT study is not available to the general public, it states most formulations of glucosamine/chondroitin are similar enough to be efficacious.


It is also noteworthy that that one ancillary part of the GAIT study is ongoing and examines whether one can halt or even reduce the progression of knee Osteoarthritis by using glucosamine and chondroitin. These exciting results will be reported in early 2008 and may shed light on the effectiveness of glucosamine/chondroitin over a longer period of time and in the more serious OA patient.2

What About The Safety Of Glucosamine and Chondroitin?

With recent studies and warnings of medication safety issues, glucosamine and chondroitin continue to demonstrate minimal if any ill effects. The most reported adverse reactions are nausea and epigastric discomfort. While diarrhea, constipation, blepharitis, palpitations and hair loss have also been mentioned, current research has not demonstrated a proven link between these effects and the use of glucosamine and chondroitin.
With glucosamine/chondroitin being structurally similar to heparin, except for one case of excessive glucosamine and chondroitin dosing, there has been unfounded concern about possible interference of anticoagulant therapy. Minimal evidence also suggests that glucosamine and chondroitin may facilitate the recurrence or spread of existing prostate cancer. Obviously, that would be a consideration for not using this usually safe supplement.
One small consideration is that chondroitin originates from bovine tracheal cartilage. Not only might there be religious limitations with Hindu patients, clinicians may also consider the possibility of mad cow disease transmission or bovine spongiform encephalopathy (BSE). However, there are no reports of this contamination in the current medical literature.3
Glucosamine is derived from the chitin in shellfish exoskeletons. Studies show that glucosamine enhances the production of proteoglycans and exhibits antinflammatory properties without inhibiting prostaglandin synthesis.4
The primary considerations against using glucosamine includes the interference of most available insulin therapies including insulin, sulfonylurea, thiazolidinediones. and metformin. In combination with chondroitin, glucosamine also may dangerously enhance warfarin and aspiring anticoagulant properties.5

What You Should Keep In Mind About Dosing And The GAIT Study

In October 2006, the Arthritis Foundation cited an ongoing study, which has found that up to 25 percent of people using glucosamine and chondroitin note improvement. It also references the long-anticipated results of the additional trial to measure reduction and lack of progression of knee Osteoarthritis.6
According to the Arthritis Foundation, supplements should contain a combination of 500 mg glucosamine and 400 mg chondroitin. One should take the glucosamine/chondroitin supplement three times a day and patients should reportedly notice results within days to weeks.7
Interestingly, the studies that examined the usage of glucosamine and chondroitin utilized different dosing regimens. The Glucosamine-Chondroitin Arthritis Intervention Trial (GAIT), which garnered support from the National Center for Complementary and Alternative Medicines and the National Institute for Arthritis and Musculoskeletal and Skin Diseases, randomized patients to a regimen of 1,000 mg of glucosamine hydrochloride, 1,200 mg of chondroitin sulfate, both glucosamine and chondroitin, 200 mg of Celebrex or a placebo for 24 weeks. Patients were allowed to take up to 4,000 mg acetaminophen daily for breakthrough pain.1
For a clinician in the working world, these results translated to worthy information in everyday practice. Ultimately, there was demonstrated relief with glucosamine/chondroitin for those with severe OA pain but the findings were not as robust for patients whose symptoms were not as advanced. However, I do feel it is more impressive to achieve pain relief for those with more advanced disease.1

Other Considerations To Be Aware Of With The GAIT Study

In an accompanying editorial in the same issue of the New England Journal of Medicine, Marc C. Hochberg, MD, MPH, pointed out several salient considerations. These considerations include a high dropout rate, which may have adversely impacted a reliable reporting of results. Dr. Hochberg also cited the high rate of response by the placebo arm, which had not been anticipated.8
Dr. Hochberg also opined that researchers should have used the Rottapharm brand of glucosamine sulfate, which was cited as effective in seven previous trials, as opposed to the chosen glucosamine hydrochloride.
In the editorial, Dr. Hochberg advised that if a patient experiences no improvement after a three-month trial, that clinicians should discontinue the glucosamine and chondroitin. He also encouraged clinicians to advise patients that utilizing glucosamine sulfate and chondroitin “may have an additive effect.”8 This was also discussed by Jellin and Gregory in the Prescriber’s Letter.3

Final Notes

My own husband, Rick, has used the generic version of glucosamine and chondroitin with impressive relief. After he researched the topic, he learned that people usually notice results after approximately a week of use although may take as long as three months. Rick prefers to buy “whatever is on sale” at the local pharmacy and has not noticed differences in the various versions. He states that if he does not take it for four to six days, his knees again begin to hurt and swell.
As a former marathoner and tri-athlete, my aging spouse of over two decades says: “For an over-the-counter remedy that is so inexpensive, it is definitely worth trying.” I concur.