A method of treating, managing, repairing or modulating inflammation associated with damage to connective tissue in humans and animals comprising administering an effective amount of a combination comprising one or more avocado/soybean unsaponifiables, glucosamine, and a chondroitin or a salt thereof to a human or animal in need thereof, wherein the combination provides a synergistic effect and wherein the combination is administered daily to reach a steady state concentration in a body fluid of the human or animal that bathes a target cell type that affects at least one of COX-2, TNF-α, IL-1β, iNOS, p38, and chemokines, and wherein the dosage is subsequently reduced in at least one of frequency and amount to maintain a desired response in the human or animal.