David T. Felson, MD, MPH
Grant Support: Dr. Felson is supported by National Institutes of Health grant AR 47785.
Potential Financial Conflicts of Interest: Grants received: Merck & Co.
Requests for Single Reprints: David T. Felson, MD, MPH, Clinical Epidemiology, A203, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118; e-mail, firstname.lastname@example.org.
Felson D.; Chondroitin for Pain in Osteoarthritis. Ann Intern Med. 2007;146:611-612. doi: 10.7326/0003-4819-146-8-200704170-00014
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Published: Ann Intern Med. 2007;146(8):611-612.
Frequent knee pain affects about 25% of adults (1), at least half of whom have osteoarthritis (2). Persons with knee and other joint pain often take over-the-counter nutritional supplements available in grocery stores, in drug stores, or online for treatment of their joint pain. The most popular supplement is a pill containing a combination of glucosamine and chondroitin. The demand for the chondroitin component of this pill alone constitutes a $1 billion-per-year market in the United States.
The primary pathology of osteoarthritis is loss of hyaline articular cartilage. Chondroitin sulfate, a glycosaminoglycan, is a constituent of a large macromolecule in cartilage called aggrecan. Glycosaminoglycans like chondroitin have a high negative charge. During cartilage compression, the negatively charged glycosaminoglycan molecules are forced into proximity, increasing the electrostatic repulsive force among them. As compression ends, the electrostatic force predominates and they move away from each other, allowing cartilage to reassume its usual thickness. Thus, aggrecan and its constituents—including chondroitin—provide compressive stiffness to cartilage. The concept of ingesting a molecule found in cartilage so that it might be incorporated into cartilage is appealing, but the logic is misleading: Glycosaminoglycans are not synthesized from intact chondroitin molecules; therefore, it is unlikely that ingested chondroitin would be incorporated intact into cartilage.
Patrick H. MacAuley
April 16, 2007
Glucosamine sulfate, never hydrochloride
Interesting editorial, but I have to comment on your statement that Glucosamine hydrochloride is the form of glucosamine most commonly used in America. The reality is that nearly all knowledgable users of stand-alone glucosamine will take Glucosamine sulfate, and only cheap products marketed to under-informed consumers will contain the hydrochloride form.
There are at least two theoretical reasons why the sulfate form should be superior: First, in some large joints glucosamine-sulfate-based compounds appear to serve as lubricants. Second, since glucosamine and sulphur are two of the most important constituents of cartilage, it would clearly seem better to take the the sulphur-containing form. (Some manufacturers claim that that it's OK to take the hydrochloride form if it's combined with Chrondoitin sulfate, but I'm skeptical, especially since so little Chondroitin sulfate is absorbed into the bloodtream.)
So even if you are correct that the hydrochloride form is more commonly used, it is used by less knowledgable users rather than serious students of nutrients. Of course, if they are getting a placebo effect from Glucosamine hydrochloride, it is fairly cheap and it doesn't appear to do any harm.
Martin T Donohoe
Portland State University
April 23, 2007
Chondroitin use contributes to global decline in shark populations
Shark cartilage serves as a major source of chondroitin.(1) The UN Food and Agricultural Organization reports that 70-80% of the world's shark fisheries are fully- to over-exploited, depleted, or in a state of collapse. (2) In the US, one of the few countries that even somewhat effectively manages any of its fisheries, the number of some species of coastal sharks has been reduced by 75-85% over the past 20 years.(2) Sharks are caught for their fins (to be used in soup), their cartilage (to be used in supplements), and their meat, as well as "inadvertently" through the use of long-line fishing. The United Nations Food and Agriculture Organization estimates that 100 million sharks, rays, and skates are fished yearly, but acknowledges that this number is too low, due to under-reporting by many of the 125+ nations engaged in the shark trade.(2) Unregulated fisheries in other countries and in international waters support a thriving, worldwide gray-market trade in shark skeletons.(2)
Shark cartilage first achieved widespread recognition through I. William Lane, whose 1992 bestseller Sharks Don't Get Cancer was promoted by a 1993 broadcast of 60 Minutes.(3) [Ironically, sharks do get cancers, including those of the cartilage.] A few years ago, the FDA took legal action to stop sales of BeneFin (one brand of shark cartilage) and two other alternative remedies produced by labs owned by Lane, claiming that such products may not be promoted and marketed as therapies until their efficacy has been proven.(3)
Nevertheless, some companies today market shark cartilage as pet neutraceuticals (e.g., Sea Pet Shark Cartilage Frosted Treats, "to enhance [your dog's] healthy joints", available at www.seapet.com).
Despite its lack of proven efficacy, Felson sees "no harm in encouraging patients to continue taking [chondroitin] as long as they perceive a benefit.(4) I disagree. In the midst of the largest global extinction since the demise of the dinosaurs 65 million years ago, when we are losing over 5,000 species per year (10,000 times the naturally- occurring rate of extinction), we must take special care to preserve all creatures and promote biodiversity.(5) Given that many currently available pharmaceutical and "neutraceutical" products are derived from or patterned after molecules found in plant and animal species, we must balance a respect for human, plant, and animal life and assure that a continuing source of effective organismal products are available for patients.
1) Arthritis Foundation. Alternative therapies: glucosamine and chondroitin sulfate. Available at http://www.arthritis.org/conditions/alttherapies/glucosamine.asp. Accessed 4/20/07.
2) Kemper S. Shark. Smithsonian 2005 (August):43-51.
3) Rivlin, MA. Bad to the bone. The Amicus Journal (Natural Resources Defense Council) 2000(Spring):12-18.
4) Felson DT. Chondroitin for pain in osteoarthritis. Ann Int Med 2007;146:611-12.
5) Donohoe MT. Causes and health consequences of environmental degradation and social injustice. Soc Sci and Med 2003;56(3):573-587.
UniversitÃ di Genova
May 2, 2007
Chondroitin for Pain in Osteoarthritis
in his editorial article in Annals of Internal Medicine (Chondroitin for pain in osteoarthritis, 2007 Apr 17;146(8):611-2) dr. David T. Felson states "At least 1 trial reported that chondroitin was more effective than total knee replacement (6), a finding that lacks credibility (6. Rovetta G. Galactosaminoglycuronoglycan sulfate (matrix) in therapy of tibiofibular osteoarthritis of the knee. Drugs Exp Clin Res. 1991;17:53-7. [PMID: 1914837]). I think that dr. Felson must properly read my paper before quoting it. This sentence is completely invented.
With best regards
Prof. Guido Rovetta UniversitÃ di Genova
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