At the ends of each of the two bones that form joints in the body is a rubbery substance called cartilage, which serves the purpose of cushioning the bone against sudden jolts. It is damage to this cartilage and the underlying bone that forms the basis of osteoarthritis, the most common arthritis of older age.
Cartilage is made up of, among other things, a family of chemicals called glycosaminoglycans. The chemical glucosamine occurs naturally in the body and is a building block for the glycosaminoglycans; chondroitin is one of a particular type of glycosaminoglycan called a proteoglycan. These compounds can be derived from natural products, particularly the shells of shellfish, or they can be synthesized.
In many European countries, glucosamine is regulated as a prescription drug, rather than as a dietary supplement. The Food and Drug Administration (FDA) has warned one glucosamine manufacturer not to claim that the supplement is effective for arthritis.
Do Not Use: There is no evidence that this supplement is effective.
Glucosamine and chondroitin (DONA, MAJESTIC EARTH) have been administered separately or together to treat osteoarthritis; there are even claims by some proponents that these supplements can reverse the course of the disease, something that the standard therapy for osteoarthritis, nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen [ADVIL, MEDIPREN, MOTRIN, NUPRIN]), has never been shown to accomplish. However, one problem facing the advocates of glucosamine is that no human clinical data exist to confirm that glucosamine actually reaches the joint or that it does so in adequate concentrations.
In the most rigorous study to date, there was no evidence of effectiveness for glucosamine, chondroitin or the combination of the two together. Public Citizen continues to recommend against the use of these supplements.
In general, glucosamine is well tolerated. There is a case report of glucosamine raising blood sugar levels, an effect also seen with high doses in animals. However, a small, randomized trial was not able to detect such an effect.Glucosamine has been associated with an allergic skin rash, and the combination of glucosamine and chondroitin has been associated with asthma.
As for all dietary supplements, questions over the purity and consistency of commercially available formulations remain. In a National Institutes of Health (NIH) trial (see “Studies show …” section), such inconsistencies were so substantial that the researchers had to manufacture the supplements themselves.
Interactions with other drugs
The U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has received seven reports suggesting an interaction between glucosamine and warfarin (COUMADIN), according to the MHRA and the U.K. Committee on Safety of Medicines (CSM). In those cases, patients who previously had stable warfarin lab monitoring values while receiving warfarin experienced an increase in those lab values after they started receiving glucosamine supplements. This means that the patients were at higher risk of bleeding. The mechanism of any interaction is unclear; however, it is recommended that patients on warfarin not take glucosamine.
The Australian Adverse Drug Reactions Advisory Committee reported that there were 12 cases of changes in lab values that developed after glucosamine was started in patients previously stable on warfarin.
The MHRA and the CSM say that patients who have seafood allergies should not use glucosamine because it is manufactured by processing crushed crustacean shells and therefore may cause an allergic reaction in such individuals.
Studies show ...
Glucosamine and/or meta-analyses
Two studies have statistically combined the randomized trials on glucosamine and/or chondroitin, a technique known as meta-analysis. In the first, restricted to glucosamine, most studies showed glucosamine to be effective in osteoarthritis, but the studies were poorly designed (the median design score was 2 on a scale of 0–8, where 8 is the best-designed study).For instance, the studies were conducted over a short time period, and there was no standardization in both diagnosis of osteoarthritis and in the measure of effectiveness of glucosamine.
A subsequent meta-analysis found efficacy in treating osteoarthritis for glucosamine and for chondroitin.However, these trials, too, were of poor methodological quality, with such major deficiencies as lack of intention-to-treat analyses (i.e., the studies included data only on those who completed the study, not on all subjects) in almost all cases. Further, the largest and best-designed studies showed the least benefit. With the great majority of these studies either funded by the manufacturers or including authors employed by the manufacturers, the authors of the meta-analysis raised the possibility of a well-documented practice known as publication bias, in which studies showing an intervention not to be effective are simply not published.
Randomized, controlled trials
Since these meta-analyses were published, five randomized, placebo-controlled trials of glucosamine have been conducted. (There is also a third meta-analysis reporting benefits for glucosamine and chondroitin,but we prefer to review the more recent studies individually.)
Three studies claim positive results. In the most widely cited, statistically significant improvements in symptom scores and on X-ray were claimed.However, the improvements in symptom scores were presented in an inconsistent fashion, making interpretation difficult.In fact, the scores reflecting knee function (almost all studies of glucosamine examine knee osteoarthritis only) reveal an absolute benefit for glucosamine of only 5 percent. The study was also unique in demonstrating, for perhaps the first time for any osteoarthritis drug, a benefit in the X-ray appearance of the knee: less narrowing of the joint, a common consequence of osteoarthritis. Again, however, the effect was very small: about 1/250 of an inch per year. In any event, the relationship between joint-space narrowing and symptoms is very weak.
A second study, also funded by the leading glucosamine manufacturer, had similar results and limitations.
In the third trial, the patients did not have X-ray-confirmed diagnoses of osteoarthritis prior to the study, the number of patients was small, the glucosamine group had had osteoarthritis for longer than the placebo group, and although reported pain scores were more improved in the glucosamine group than in the placebo group, the drug had little or no impact on measures of joint function.On the other hand, two somewhat smaller, well-conducted trials showed no benefit whatsoever for glucosamine compared to placebo on either pain or an array of indices of joint function.,
Three studies on chondroitin have been published since these meta-analyses, and none is sufficient to shift our view of the efficacy of these products. Two studies claim effectiveness for chondroitin, but one improperly combined the placebo groups from two separate studies and the other was not designed in a manner that allowed clear comparison between chondroitin and the placebo. In the third, the intention-to-treat analysis does not reach statistical significance.
Because of the ongoing controversy over the efficacy of these supplements,,the NIH conducted a six-month randomized trial comparing glucosamine and chondroitin, alone and together, to a placebo. The study examined both pain relief and the progression of osteoarthritis of the knee. No statistically significant difference was found in effectiveness between any of these products and a placebo on the main pain measure.
In 2009, a Drug and Therapeutics Bulletin article looked at the use of glucosamine in osteoarthritis. According to the article:
The National Institute for Health and Clinical Excellence (NICE) guideline on osteoarthritis does not recommend the use of glucosamine for the treatment of patients with this condition. It found that “overall, those trials which used glucosamine sulfate as a single dose of 1,500mg, rather than hydrochloride 500mg tds, showed a small benefit over placebo for treatment of knee OA [osteoarthritis]. … Evidence to support the efficacy of licensed glucosamine hydrochloride as a symptom modifier is poor … For the non-licensed product (glucosamine sulfate), the evidence is not strong enough to warrant recommending that it should be prescribed on the NHS. … A wide range of incremental cost-effectiveness ratios reported and the poorest estimates of efficacy would take it beyond the threshold of affordability in the NHS.
In August 2011, the journal Archives of Physical Medicine and Rehabilitation published results of another study. This study examined the effect of an NSAID, glucosamine or placebo together with strength training on reduced pain and muscle strength in patients with knee osteoarthritis. The authors found that the improvements in muscle strength and the small decrease in muscle pain in patients taking an NSAID or glucosamine compared to improvements in patients taking a placebo were not large enough to justify taking these medications.
A recent Journal of Parenteral and Enteral Nutrition (JPEN) systematic review revealed that, with a few possible exceptions, dietary supplements offer no benefits to well-nourished adults eating a Western diet and, in many cases, may be harmful. The results of this study reinforce Worst Pills, Best Pills News’ longstanding view that there is little evidence that dietary supplements are either safe or effective.
The study authors concluded that with the possible exception of vitamin D in elderly patients and omega-3 fatty acids in patients with a history of cardiovascular disease, no data support the widespread use of dietary supplements in the U.S. and other Western countries. Indeed, the data suggest that certain commonly used dietary supplements, including beta-carotene, vitamin A and vitamin E, may be harmful. We agree.