1. Dietary Supplements for Joints W. Rose Last updated 2008

2. Proteoglycan Complex. Key component of the ground substance of cartilage. Made of proteoglycans (aggrecans) attached to a hyaluronic acid backbone. Each proteoglycan includes a protein backbone (the start of which is shown in green) and glycosaminoglycan side chains (chondroitin sulfate, keratan sulfate). Chondroitin sulfate, keratan sulfate, and hyaluronic acid are all glycoaminoglycans; hylauronic acid is an unsulfated GAG. Total molecular weight of the complex: up to 3x10 6 daltons. Figure: Marieb & Hoehn 4.7. Also: Jim Swan, http://webanatomy.net/anatomy/

3. Images: Craig W. Wiesenhutter www.cdaarthritis.com/images_slideswww.cdaarthritis.com/images_slides Also: Jim Swan, http://webanatomy.net/anatomy/ Proteoglycan complex. Hyaluronic acid (or hyaluronate) backbone with proteoglycans (aggrecans) attached. Found in extracellular matricx of cartilage. Chondrocyte shown for reference. Another view of proteoglycan complexes. Proteoglycan (aggrecan) structure. Protein backbone with a mix of up to about 30 keratan sulfate side chains and up to about 100 chondroitin sulfate side chains.

4. Popular “dietary supplements” sold as treatment for OA: chondroitin and glucosamine. Chondroitin one subunit; portion derived from glucosamine highlighted www.genome.jp/Fig/compound/C00607.gif Glucosamine www.genome.jp/Fig/compound/C00043.gif Dietary supplements need not prove efficacy or even content of the supplement. Burden is on gov’t to prove it is not safe. Glucosamine is a component of chondroitin. Chondroitin is a glycosaminoglycan (GAG): large, negatively charged (hence hydrophilic), gel-forming polysaccharide. Gives cartilage much of its ability to withstand compression. Keratan sulfate, hyaluronic acid are also GAGs. At physiological pH, these molecules are neg. charged, since some of the hydroxyls dissociate.

5. Good studies show these supplements don’t help. NEJM, Feb. 2006: Glucosamine, chondroitin, gluc/chon combination, Celebrex, or placebo. Knee OA. Only celebrex better than placebo. (Suggestion that a “moderate to severe knee pain” subgroup may be helped more by supplements than by placebo, but the group was small so further study needed.) Ann Int Med 2008: Glucosamine sulfate vs placebo. Hip OA. Glucosamine not better than placebo. Arthr Rheum Oct 2008: Glucosamine, chondroitin sulfate, combination, Celebrex, or placebo. Knee OA. Follow-up to the hint in the NEJM 2006 study. None of the treatments reduce disease progression.

6. Glucosamine sulfate is no better than placebo in reducing the symptoms or progression of hip OA, according to a randomized, double-blind, placebo-controlled trial in the Netherlands (2008). 222 patients were treated for two years with glucosamine sulfate or placebo. Primary outcome measures were hip pain, hip function, and joint space (assessed radiographically, i.e. by X-ray images). (Joint space decreases as OA progresses.) Glucosamine sulfate was no better than placebo for any of the main outcome measures. Ann Intern Med. (2008) 148: 268-277.

7. The best current evidence is that chondroitin sulfate does not reduce joint pain in osteoarthritis. However, some patients are convinced that it helps, which could be because of a placebo response or even a therapeutic response resulting from enhanced absorption or limited metabolism of chondroitin. Because no frequent or severe adverse effects have been reported, chondroitin sulfate should not be considered dangerous. If patients say that they benefit from chondroitin, I see no harm in encouraging them to continue taking it as long as they perceive a benefit. D. Felson, MD, MPH Ann Intern Med (2007) 146: 611-612. Chondroitin www.3dchem.com/imagesofmolecules/Chondroitin.jpg