Chondroitin for Pain in Osteoarthritis

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.

There are 2 other practical concerns about the potential efficacy of chondroitin sulfate. First, because chondroitin is a large macromolecule, only about 12% to 13% of ingested chondroitin is absorbed intact into the bloodstream (3). Second, while chondroitin therapy supposedly targets cartilage, osteoarthritis affects the whole joint, not just cartilage. Pathologies include bone …