Glucosamine hydrochloride, which is used to reduce clinical signs of osteoarthritis, is believed to favorably modulate the metabolic activity of chon-
drocytes. In vitro and animal studies suggest that it helps preserve cartilage by stimulating synthetic activity and inhibiting catabolic enzymes.

S-adenosylmethionine (SAMe), a nutraceutical with potent antioxidant and antiinflammatory activity, is also used in the treatment of joint disorders to reduce pain and improve joint function. Unlike glucosamine, however, very little is known about SAMe's direct effect on cartilage. The purpose of this study was to examine whether glucosamine combined with SAMe would provide more effective treatment for joint disorders.

In vitro studies were conducted examining the synthesis and catabolism of cartilage matrix macromolecules. The effects of glucosamine and SAMe under conditions of stress were also examined by simulating early osteoarthritic conditions in vitro via partial proteoglycan depletion and by examining the response of articular cartilage from an osteoarthritic joint. The authors found that exposure of chondrocytes to SAMe by itself demonstrated a dose-dependent stimulation of glycosaminoglycan (GAG) synthesis. However, no response was seen with glucosamine alone. When glucosamine and SAMe were combined, a synergistic effect was seen, with a 15% to 20% greater increase in activity than when either agent was tested alone. In testing for anticatabolic activity, glucosamine, SAMe, and both agents combined all showed activity after 72 hours, with combined glucosamine and SAMe again showing synergistic effects over either agent used alone. In the tests using conditions of stress, glucosamine and SAMe combined showed a significantly greater effect on matrix synthesis than either agent alone.

COMMENTARY: There is mounting evidence that glucosamine and s-adenosylmethionine (SAMe) reduce pain and improve joint function in osteoarthritis. Most clinical trials have studied primary osteoarthritis involving humans. The results of this study, suggesting that the combination of SAMe and glucosamine is more efficacious than either agent used alone, is interesting and potentially significant but must be proven by clinical trials. Osteoarthritis in dogs commonly has a contributing, underlying component (secondary osteoarthritis), such as cruciate ligament disease, hip dysplasia, elbow dysplasia, and osteochondritis dissecans; in humans, osteoarthritis often has no identifiable underlying component and is referred to as primary arthritis. These common joint disorders in dogs that lead to secondary osteoarthritis have been most consistently managed by weight loss, surgery for the underlying component, and a formal postoperative rehabilitation program. It may be that initial medical management of the secondary osteoarthritis may not be as effective as with the primary osteoarthritis that is common in humans. Good clinical trials for dogs are necessary, and this distinction should be kept in mind.

Advantageous use of glucosamine combined with S-adenosylmethionine in veterinary medicine: Preservation of articular cartilage in joint disorders. Lippiello L, Prudhomme A. INTl J APPL RES VET MED 3:6-12, 2005.