I have a confession to make. I have been taking 1200 mgs of glucosamine sulfate for the past 5-6 years for my knee cartilage. I do not presently have osteoarthritis, but I am trying to stave it off by taking this supplement.
Does this supplement work? That’s hard to say for certain because the studies disagree. There are theoretical reasons to suspect that glucosamine would help with cartilage deposition. Cartilage is very rich in a group of sticky, sugary compounds called “glycosaminoglycans,” which have the unfortunate acronym of GAGs. GAGs consist of repeating two-sugar motifs, and the building block for the vast majority of these two-sugar motifs is glucosamine. Therefore, glucosamine is a main building block of a prominent component of cartilage.
What about chrondroitin? Chondroitin is a GAG that usually comes attached to a protein. This complex of GAG + backbone protein is called a “proteoglycan.” The chondroitin you get in the store is a repeating polymer of a two-sugar motif, and this complex molecule is either degraded in your digestive system by bacteria, or by our own gastrointestinal tract. The degradation and absorption of chondroitin probably varies considerably from person to person. If chondroitin is absorbed then the building blocks of chondroitin can potentially help build cartilage, since chondroitin-containing proteoglycans are important structural components of cartilage. There is also the possibility that chondroitin precursors prevent the breakdown of cartilage.
In 2006, a good-sized study called the GAIT study was published in the New England Journal of Medicine (Clegg, D.O. et al. (2006). Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New Eng. J. Med. 354(8):795-808). In this study, 1583 patients with symptomatic knee osteoarthritis were randomly assigned to different treatment subgroups. These groups were:
a) chondroitin sulphate alone (400 mg 3x a day)
b) glucosamine hydrochloride alone (500 mg 3x a day)
c) combined glucosamine hydrochloride/chondroitin sulphate (same doses but combined)
d) celecoxib (Celebrex®) (200 mg per day)
e) placebo (inactive dummy tablet)
Daily dosages for glucosamine and chondroitin were 1500 mgs and 1200 mgs, respectively. The efficacious dosage for these supplements have yet to be determined. Therefore, these dosages are a best guess. Celecoxib was included as a positive control for the GAIT study, since celecoxib is FDA approved for the management of osteoarthritis pain. Therefore, investigators therefore expected participants in this group to experience some pain relief, which would serve to validate the results of the GAIT study.
The GAIT study found that when patients were divided into two groups based on pain levels, 1,229 had mild pain and 354 had moderate to severe pain. With regard to the effectiveness of these supplements, neither glucosamine nor chondroitin sulphate either on their own or in combination were effective in reducing pain. However, when only those patients with moderate to severe pain was analyzed the combination of glucosamine and chondroitin sulphate was effective for pain relief. Unfortunately, no cartilage thickness studies were performed to determine if the supplements augment cartilage thickness. The GAIT study was publicly funded, and therefore, accusations of conflict of interest could not be used to discredit this study.
in 2005, results from the GUIDE study were presented at the 2005 Annual Meeting of the American College of Rheumatology. This study was funded by glucosamine manufacturers and examined of pain and mobility in 318 osteoarthritis sufferers between the ages of 45 and 75 at 13 European hospitals. Participants in this study were divided into three groups:
a) glucosamine sulphate in soluble powder form 1500mg daily
b) acetaminophen (e.g. Tylenol® and paracetamol) 3000mg daily
In addition, subjects in all three groups were allowed to take ibuprofen as needed as a ‘rescue’ for pain relief.
The GUIDE study found that glucosamine sulphate and acetaminophen were more effective in reducing pain than placebo. Patients who took glucosamine sulphate experienced greater pain relief than patients on acetaminophen.
The GUIDE and GAIT studies were positive for glucosamine and chondroitin, but there are negative studies too. In October 2004, Jolanda Cibere and others published a study in the journal Arthritis Care and Research in which they gave glucosamine or a placebo to arthritis suffers and then discontinued them. 42% of the patients receiving the placebo experienced a disease flare-up and 45% of the glucosamine-receiving patients experienced a flare-up. Also, the time to disease flare was not significantly different in the glucosamine compared with placebo group. Thus Cibere and others concluded that “this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate.”
The bottom line on all this is the glucosamine and chondroitin perform inconsistently in controlled studies. When poor-quality studies are excluded, glucosamine seems to delay arthritis. The highly respected Cochrane Library published a summary of human clinical trials with glucosamine and when the poor-quality trials were excluded, Towheed and his colleagues concluded that glucosamine provided relief of the symptoms of arthritis and also, based on X-rays, helped delay the onset of osteoarthritis.
However, the European Food Safety Authority reviewed over 60 articles on glucosamine and came to a completely different conclusion. In 2012, the EFSA concluded that “The Panel concludes that a cause and effect relationship has not been established between the consumption of glucosamine and maintenance of normal joint cartilage in individuals without osteoarthritis.”
In 2009, in the Journal, Arthroscopy, Vangsness, Spiker, and Erickson came to a somewhat blasé conclusion, “glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate have individually shown inconsistent efficacy in decreasing OA pain and improving joint function.”
The long and the short of it is that these supplements might work. Furthermore, my best guess at this point is that they probably work better for some people than for others. So should you take glucosamine or even chondroitin? All our information at this point says that it is safe to do so. No serious or even moderate side effects have been observed by taking these supplements. Secondly, they might work for some people. How do know if you are one of them? By taking the supplement.
I realize that this post is probably very unsatisfying to many of you, but some are very enthusiastic about glucosamine and chondroitin, and I think that this enthusiasm needs to be tempered by a hard dose of reality. There is much we simply do not know at this time about the efficacy of these supplements, and more work needs to be done before we can say anything definitive about them. A recent study shows that large doses of chondroitin (1200 mgs) are effective at reducing symptoms in patients with osteoarthritis of the knee, but given the vagaries of chondroitin absorption (see above), it is unlikely that we can make any hard and fast conclusions about it.
One more note about these supplements. Several studies have shown that the quality of over-the-counter glucosamine vary considerably. Be careful what you buy and from whom you buy your supplements. Consumer Reports has shown that some supplements are even spiked with prescription drugs! So caveat emptor and do not believe the marketer’s own statements about their supplements.