| The Research Status of Glucosamine Sulfate By Dr. James Meschino, D.C., MS About Dr. Meschino James Meschino,DC,MS, holds a master's degree in science with specialties in nutrition and biology. He is on the board of advisors of the Academy of Anti-Aging Research and is the clinical and research director for the RenaiSanté Institute of Integrative Medicine. He is an associate professor in the division of graduate studies and research at the Canadian Memorial Chiropractic College, and a postgraduate faculty member of the American Council on Exercise. He was also the attending chiropractor at the Ryerson University Health Centre from 2000-2001. Osteoarthritis has been reported to affect 40 million Americans, involving more than 13 percent of the population. Eighty percent of those over the age of 50 are affected to some degree, and show radiographic evidence of osteoarthritic changes.1 A contributing cause of osteoarthritis is now thought to include the age-related decline in the body's synthesis of glucosamine, which appears to become pronounced by 45 to 50 years of age.2 Glucosamine sulfate is normally synthesized by chondrocytes and serves as the precursor to the production of N-acetyl-galactosamine sulfate, an essential component of chondroitin sulfate. Chondroitin sulfate forms the ground substance (glycosaminoglycans, proteoglycans or mucopolysaccharides) of joint cartilage.3 Thus, any reduction in glucosamine sulfate synthesis results in a decline in joint cartilage (articular cartilage) ground substance production, with subsequent joint space narrowing and arthritic degeneration.2 In the body, glucosamine is synthesized by the conversion of fructose-6 phosphate to glucosamine-6 phosphate by the enzyme, fructose-6 phosphate amide transferase, in the hexosamine biosynthetic pathway.3 As we age, it appears that the fructose-6 phosphate amide transferase enzyme concentrations decline or this enzyme becomes less active, resulting in the noted reduction in glucosamine synthesis seen with aging.2 Since the early 1980s, researchers have conducted a large number of clinical and experimental investigations to determine if oral glucosamine sulfate supplementation can compensate for the age-related decline in glucosamine synthesis, and thereby block the progression of osteoarthritis or reverse or repair any existing joint cartilage damage.4,5 In the past 20 years glucosamine sulfate has been the subject of more than 300 scientific investigations and over 20 double-blind clinical studies.2 In a recent meta-analysis addressing the efficacy of glucosamine sulfate for the treatment of osteoarthritis, researchers indicated that glucosamine supplementation was shown to be highly effective in the treatment of osteoarthritis in all 13 double-blind clinical trials that met the inclusion criteria.6 Absorption and Metabolism of Oral Glucosamine Sulfate Glucosamine is a small and simple molecule that is readily absorbed from the gastrointestinal tract. Studies demonstrate that 90-98 percent of glucosamine sulfate is absorbed intact from the intestinal tract. By contrast, less than 13 percent of chondroitin sulfate is absorbed from the intestinal tract, making it significantly less effective than glucosamine sulfate as an intervention in the prevention and management of osteoarthritis.7-11 Once absorbed from the gut, glucosamine circulates through the bloodstream, where it can be taken up by cartilage cells (chondrocytes) and used to synthesize N-acetyl-galactosamine sulfate in the production of cartilage ground substance (glycosaminoglycans).3,12 The ground substance in joint cartilage fills in the gaps between the collagen fibers, which run parallel to each other within the cartilage. As an analogy, the collagen fibers are like the bricks of the cartilage structure, and the glycosaminoglycans are like the mortar between the bricks. Not only does glucosamine sulfate supplementation stimulate the synthesis of glycosaminoglycans, but it stimulates the synthesis of collagen by chondrocytes.13 As well, glucosamine sulfate is required for the synthesis of hyaluronic acid by the synovial membrane of the joint. Hyaluronic acid increases the viscosity of the synovial fluid and serves to reduce the wear-and-tear stress on the articular cartilage and related joint structures. Thus, glucosamine may be helpful in preventing, reversing or stabilizing the osteoarthritic process by stimulating the synthesis of glycosaminoglycans, collagen and hyaluronic acid.13,14 Essentially all of the research on glucosamine has employed the use of glucosamine sulfate, the only treatment approved for osteoarthritis in more than 70 countries around the world, used by millions of people for this purpose for more than 20 years.2 Glucosamine sulfate also delivers the mineral sulfur (hence the name glucosamine sulfate) to the joint cartilage. It has been recognized for many years that sulfur is a vital nutrient for the maintenance of joint cartilage. Sulfur is required to stabilize the connective tissue matrix of cartilage, tendons, and ligaments.15-19 As such, the use of glucosamine sulfate provides the joint structures with the mineral sulfur and glucosamine. This form of glucosamine offers a double benefit in the management of osteoarthritis cases. Other forms of glucosamine are present in the commercial marketplace, such as N-acetyl-glucosamine and glucosamine hydrochloride. There is presently insufficient evidence to support their use and neither one of these forms provides the addition of the mineral sulfur, which has shown to be of value in osteoarthritis cases.2 Clinical Studies with Glucosamine Sulfate Glucosamine sulfate has been the subject of more than 300 scientific investigations and over 20 double-blind clinical studies.2 In a recent meta-analysis of glucosamine clinical trials in the treatment of osteoarthritis, McAlindon and colleagues indicated that all 13 studies that met the inclusion criteria for double-blind, placebo-controlled trials of greater than four weeks' duration; using global pain score or the Lequesne index joint as the primary outcome measure and considered the trial positive if improvement in the treatment group was equal to or greater than 25 percent compared with the placebo group), were classified as positive, demonstrating that glucosamine supplementation is highly effective in the treatment of osteoarthritis. This meta-analysis revealed that glucosamine supplementation reduced the symptoms and signs of osteoarthritis by 40.2 percent on average, compared with the placebo.6 Glucosamine sulfate supplementation has also been investigated in head-to-head studies against nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis. In a number of these trials, glucosamine supplementation was shown to produce better results than ibuprofen and other NSAIDs in relieving the pain and inflammation of osteoarthritis. Unlike many NSAIDs, glucosamine has not been shown to produce any of the adverse side-effects that are frequently encountered with the use of NSAIDs (gastritis; peptic ulcer; GI bleeding and erosion of the intestinal lining; liver and kidney toxicity; and tinnitus).20-24 In a recent therapeutic investigation involving 178 Chinese patients suffering from osteoarthritis of the knee, the group given a daily dose of 1500mg of glucosamine sulfate demonstrated better results than did the group given ibuprofen at 1200mg per day (NSAID) with respect to reduction in symptoms of osteoarthritis. In this study, glucosamine sulfate was shown to be better tolerated than ibuprofen. Sixteen percent of the ibuprofen group dropped out due to adverse side-effects from the drug. A six-percent dropout rate occurred in the glucosamine group. The authors of the study concluded that glucosamine sulfate was a selective intervention for osteoarthritis, as effective on the symptoms of the disease as NSAIDs but significantly better tolerated. As such, glucosamine sulfate seems particularly indicated in the long-term treatment needed in osteoarthritis.25 |
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