Glucosamine is a naturally occurring amino sugar found ubiquitously in glycoproteins and glycosaminoglycans. Glycosaminoglycans, formerly named mucopolysaccharides, are an integral component of all connective tissues.Connective tissue, a fibrous type of body tissue, has various functions. It supports and connects internal organs (ligaments), forms bone, cartilage, and the walls of blood vessels, attaches muscles to bones (tendons), and replaces tissues that have been damaged following injury. The two main components of connective tissue are collagen and proteoglycans. Collagen is the strong, fibrous protein that physically connects our tissues. Proteoglycans are large carbohydrate-rich structures, resembling a bottlebrush in three-dimensional structure, i.e., a central protein rod with many strings of glucosamine-containing glycosaminogly-cans extending outwards. Proteoglycans hold large amounts of water forming a stiff gel by virtue of their dense negative charges from sulfates. Proteoglycans are linked to collagen fibers to help form connective tissues, and proteoglycans provide resiliency, load distribution, shock-absorbing, compressive and lubricating properties to connective tissues and joints. Glycosaminoglycans and proteoglycans are continuously being formed and replaced in connective tissues. Remodeling of connective tissues is also continuous, albeit slowly, with turnover half-lives of almost two years in healthy human joints. Turnover is accelerated in wound healing, arthritic joints, and burns.
New synthesis of glycosaminoglycans has clinical importance in skin during normal wound healing, in bone during fracture repair and osteoporosis, and in joints. In these instances, glycosaminoglycan synthesis is necessary for healing, and enhancement of glycosaminoglycan and proteoglycan deposition may improve tissue repair. Glycosaminoglycans are synthesized primarily by fibroblasts (skin, tendons, ligaments), osteoblasts (bone), and chondrocytes (cartilage). Thus, the cell™s ability to manufacture glycosaminoglycans and secrete proteoglycans is crucial during any healing or joint disease process. The availability of glucosamine is the key, rate-limiting step in glycosaminoglycan and proteoglycan synthesis in all connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Only with sufficient glucosamine, the synthesis can proceed. The body has a long metabolic pathway to synthesize a glucosamine derivative, UDP-N-acetylglucosamine, which is used for glycosaminoglycan synthesis. In addition, exogenous, i.e., dietary, glucosamine serves as an immediate precursor for glycosaminoglycan synthesis, and also stimulates incorporation of other precursors into the connective tissue matrix. Chondroitin sulfate, a glycosaminoglycan formed in the body, is also used for the synthesis and maintenance of connective tissue, primarily within the cartilage matrix. In addition, chondroitin sulfate protects existing cartilage by reducing water loss from the matrix and by inhibiting the enzymatic breakdown of the cartilage. The overlapping activities as well as functional differences of glucosamine and chondroitin sulfate offer several advantages for combined supplementation. Although glucosamine is a precursor for chondroitin synthesis, this process requires large amounts of metabolic energy. Dietary preformed chondroitin sulfate spares the use of glucosamine for this purpose. Instead glucosamine can be used for formation of other important glycosaminoglycans and proteoglycans. When adequate chondroitin sulfate is thus available to help protect tissues from premature breakdown, glucosamine can more readily stimulate synthesis of healthy new tissue. Glucosamine is almost universally found in small amounts in most foods.