In North America, the medical profession until recently took a more guarded view of glucosamine research, which has largely been performed in Europe and Asia. Concerns over research methodology and the validity of clinical findings have been raised, but it has been widely accepted that glucosamine is highly bioavailable (26 percent bioavailability after first pass through the liver to enter the bloodstream), and thus has the potential to slow or reverse osteoarthritic processes.26 These reports laid the foundation for the groundbreaking study published by Reginster, et al., in 1999 and 2001, published in Arthritis and Rheumatology (1999;42, supplement) and Lancet (2001;357). The three-year randomized study by Dr. Reginster was a large analysis that was placebo-controlled, double-blind, and prospective in nature. It involved 212 patients with knee osteoarthritis. Weightbearing and anteroposterior radiographs of each knee were obtained at one and three years, and joint space width was also measured. Symptom and functional status were scored every four months using the Western Ontario and McMaster University Osteoarthritis index (WOMAC). The two groups had comparable baseline status, but after three years there was no further joint space narrowing in the glucosamine group. The placebo group had further joint space narrowing and objective evidence of disease progression. Subject symptoms worsened in the placebo group, but the group taking glucosamine realized a marked reduction in symptoms of osteoarthritis over the three-year period. The authors concluded that glucosamine sulfate supplementation significantly reduced progression of knee osteoarthritis. Patients in the glucosamine group did not experience any untoward side-effects.27,28 "It is time for (medical doctors) to accommodate the possibility that many nutritional products may have valuable therapeutic effects and to regain the credibility of the public at large,"41 states the Lancet editorial. Other Clinical Uses of Glucosamine The clinical use of glucosamine supplementation may extend beyond the treatment of osteoarthritis. Glucosamine sulfate is also required for the synthesis of other glycosaminoglycans that are integral components of the basement membrane below the skin, intestinal tract lining and blood vessels. As reviewed by McCarty, glucosamine supplementation can be used to enhance wound healing (e.g., postsurgical) by stimulating the synthesis of hyaluronic acid. Experimental studies and human anecdotal evidence support this application.29 Glucosamine sulfate has also been used in a clinical trial involving 50 patients with temperomandibular disorders stemming from internal derangement and a diagnosis of osteoarthritis. These patients experienced decreased joint noises, pain and swelling after the administration of therapeutic doses of glucosamine and chondroitin sulfate.30 Experts in this area conclude, however, that adding chondroitin to glucosamine administration has not been shown to further improve the benefits available from glucosamine alone. At this time, the addition of chondroitin sulfate is seen to impose additional cost with no added benefit.13 There is also evidence to suggest that glucosamine sulfate supplementation may be beneficial as part of a nutritional regime to aid in the management of inflammatory bowel diseases. Experimental studies and human anecdotal evidence suggests that this may be the case. It is proposed that glucosamine supplementation can strengthen the basement membrane of gut blood vessels helping to prevent leakage of blood into the intestinal lumen, which may otherwise trigger an inflammatory immune reaction. Further, glucosamine has been shown to have a healing effect on the mucosal lining of the G I tract itself. Anecdotal evidence supports the trial of glucosamine in both Crohn's disease and ulcerative colitis.31,38 As well, the decline in glucosamine sulfate synthesis with age may imply that a prudent anti-aging strategy may be to use a low-to-moderate dose of glucosamine sulfate (500mg per day) as a prevention strategy beginning at 45-50 years of age. This intervention may help to prevent or minimize the age-related biochemical changes that are linked to the development of osteoarthritis, helping to preserve quality of life to a significant degree. This practice may also serve to reduce the chances of capillary fragility that is associated with risk of stroke and vein disorders, also seen with increasing frequency with advancing age. Finally, it should be noted that the heparan sulfate (a glycosaminoglycan made from glucosamine sulfate) content of ground substance between body cells has also been shown in animal experiments to reduce the ability of cancer cells to metastasize. The metastatic capacity of cancer cells tends to correlate with their ability to produce heparanase enzyme. Heparanase enzyme eats through the heparan sulfate ground substance (mortar) between cells, through the secretion of heparanase enzyme. Once again, glucosamine sulfate is required for the optimum synthesis of heparan sulfate, thickening the mortar between cells and making it more difficult for heparanase enzyme to break it down. With the realization that heparan sulfate production may decline as we age due to reduced glucosamine sulfate synthesis, the prophylactic administration of glucosamine may also be of value in these facets of disease prevention.32-37 Side-Effects, Toxicity and Contra-Indications to the Use of Glucosamine Reported short-term adverse side-effects from the use of glucosamine are generally mild and infrequent. These include mild gastrointestinal upset, drowsiness, skin reactions, and headache.26 Glucosamine sulfate has been shown to be non-toxic at prescribed doses.14 Patients allergic or sensitive to sulfa drugs or sulfate-containing food additives can safely take glucosamine sulfate. The word "sulfate" in this instance indicates the presence of the mineral sulfur, not the sulfa compounds used in sulfa drugs and sulfate-containing food additives. All cells of the body contain the mineral sulfur and thus, it is not possible to be allergic to this mineral. However, glucosamine sulfate is manufactured from the chitin exoskeleton of shellfish, such as lobster crab and shrimp. Therefore, it is conceivable that a person with a severe allergy to shellfish may be sensitive to the use of glucosamine, although the pharmaceutical grade of glucosamine is generally devoid of shellfish contaminants. Nevertheless, caution should be exercised in these cases.2,14 Some preliminary animal experiments and human trials on healthy people reveals that glucosamine supplementation may increase insulin resistance in some by down-regulating the synthesis of insulin receptors by the nuclear DNA.39 In large clinical trials this has not surfaced as a concern, and no indication of pronounced glucose intolerance has been demonstrated in the many well-documented glucosamine studies, including one in Lancet and the glucosamine meta-analysis appearing in JAMA.22,40 It is advisable for diabetic and pre-diabetic patients to have their blood glucose monitored during the first few weeks of glucosamine sulfate supplementation. These conditions are not an absolute contra-indication to the use of glucosamine. Dosage In regards to the treatment of osteoarthritis, the usual daily dosage of glucosamine sulfate is 1500mg, which can be taken all at one time28 or in divided doses of 500mg per dose.2,14 Individuals taking diuretic drugs may require an additional 500mg per day to compensate for the increased excretion rate. Individuals weighing more than 200 pounds may also be advised to up their dosage to 2000mg per day.2 |
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