Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of the polysaccharides chitosan and chitin, which compose the exoskeletons of crustaceans and other arthropods, cell walls in fungi and many higher organisms. Glucosamine is one of the most abundant monosaccharides.. In the US it is one of the most common non-vitamin, non-mineral, dietary supplements used by adults.
Glucosamine was first prepared in 1876 by Georg Ledderhose by the hydrolysis of chitin with concentrated hydrochloric acid. The stereochemistry was not fully defined until the 1939 work of Walter Haworth. D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all nitrogen-containing sugars. Specifically, glucosamine-6-phosphate is synthesized from fructose 6-phosphate and glutamine as the first step of the hexosamine biosynthesis pathway. The end-product of this pathway is UDP-N-acetylglucosamine (UDP-GlcNAc), which is then used for making glycosaminoglycans, proteoglycans, and glycolipids.
As the formation of glucosamine-6-phosphate is the first step for the synthesis of these products, glucosamine may be important in regulating their production; however, the way that the hexosamine biosynthesis pathway is actually regulated, and whether this could be involved in contributing to human disease remains unclear.
It may take weeks to months before improvements in symptoms are noticed when taking glucosamine.
Glucosamine is a popular alternative medicine used by consumers for the treatment of osteoarthritis (OA). Glucosamine is also extensively used in veterinary medicine as an unregulated but widely accepted supplement.
A meta-analysis published in the British Medical Journal found that alone or in combination glucosamine and chondroitin were no better than placebo for joint pain or for narrowing of joint spacing.
Adverse effects, which are usually mild and infrequent, include stomach upset, constipation, diarrhea, headache and rash.
The bioavailability of glucosamine sulfate is around 20%.
Glucosamine is an essential substrate in the natural formation of the GAG matrix.
Glucosamine is thought to stimulate synovial production of hyaluronic acid and is also claimed to inhibit cartilage degrading liposomal enzymes.
Multiple clinical trials in the 1980s and 1990s, all sponsored by the European patent-holder, Rottapharm, demonstrated a benefit for glucosamine. However, these studies were of poor quality due to shortcomings in their methods, including small size, short duration, poor analysis of drop-outs, and unclear procedures for blinding. Rottapharm then sponsored two large (at least 100 patients per group), three-year-long, placebo-controlled clinical trials of the Rottapharm brand of glucosamine sulfate. These studies both demonstrated a clear benefit for glucosamine treatment. There was not only an improvement in symptoms but also an improvement in joint space narrowing on radiographs. This suggested that glucosamine, unlike pain relievers such as NSAIDs, can actually help prevent the destruction of cartilage that is the hallmark of osteoarthritis. On the other hand, several subsequent studies, independent of Rottapharm, but smaller and shorter, did not detect any benefit of glucosamine.
Due to these controversial results, some reviews and meta-analyses have evaluated the efficacy of glucosamine. Richie et al. performed a meta-analysis of randomized clinical trials in 2003 and found efficacy for glucosamine on VAS and WOMAC pain, Lequesne index and VAS mobility and good tolerability.
Recently, a review by Bruyere et al. about glucosamine and chondroitin sulfate for the treatment of knee and hip osteoarthritis concludes that both products act as valuable symptomatic therapies for osteoarthritis disease with some potential structure-modifying effects.
This situation led the National Institutes of Health in the U.S.A. to fund a large, multicenter clinical trial (the GAIT trial) studying reported pain in osteoarthritis of the knee, comparing groups treated with chondroitin sulfate, glucosamine, and the combination, as well as both placebo and celecoxib. The results of this 6-month trial found that patients taking glucosamine HCl, chondroitin sulfate, or a combination of the two had no statistically significant improvement in their symptoms compared to patients taking a placebo. But this concern is not shared by pharmacologists at the PDR who state, "The counter anion of the glucosamine salt (i.e. chloride or sulfate) is unlikely to play any role in the action or pharmacokinetics of glucosamine". In response to these conclusions, Dr. J-Y Reginster in an accompanying editorial suggests that the authors failed to apply the principles of a sound systematic review to the meta-analysis, but instead put together different efficacy outcomes and trial designs by mixing 4-week studies with 3-year trials, intramuscular/intraarticular administrations with oral ones, and low-quality small studies reported in the early 1980s with high-quality studies reported in 2007.
However, currently OARSI (OsteoArthritis Research Society International) is recommending glucosamine as the second most effective treatment for moderate cases of osteoarthritis. Likewise, recent European League Against Rheumatism practice guidelines for knee osteoarthritis grants to glucosamine sulfate the highest level of evidence, 1A, and strength of the recommendation, A.
A report by the UK's Arthritis Research Campaign concluded that:
Despite some mixed results, the majority of trials that have evaluated the effectiveness of glucosamine sulphate demonstrated significant clinical benefits when compared to placebo or NSAIDs. Evidence from trials on glucosamine hydrochloride is scarce and much less convincing. The medication, in both sulphate and hydrochloride preparations, appears to be safe with only mild and infrequent adverse effects. The U.S. National Institutes of Health is currently conducting a study of supplemental glucosamine in obese patients, since this population may be particularly sensitive to any effects of glucosamine on insulin resistance.Europe
In most of Europe, glucosamine is approved as a medical drug and is sold in the form of glucosamine sulfate. and recent OARSI (OsteoArthritis Research Society International) guidelines for hip and knee osteoarthritis also confirm its excellent safety profile.See also
Chitosan Chitobiose Chondroitin sulfate Methylsulfonylmethane References
External links
Glucosamine article, Mayo Clinic General Glucosamine and Chondroitin Sulfate information from the Arthritis Foundation. "UDP-N-acetylglucosamine Biosynthesis," Diagram including IUBMB nomenclature and links. PDR Health Summary of drug information on glucosamine from the publishers of the Physician's Desk Reference. "Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)," ClinicalTrials.gov registration and information. "Effects of Oral Glucosamine on Insulin and Blood Vessel Activity in Normal and Obese People," ClinicalTrials.gov information. "NIH News: Efficacy of Glucosamine and Chondroitin Sulfate May Depend on Level of Osteoarthritis Pain," Wednesday, February 22, 2006. "Glucosamine and Chondroitin for Arthritis: Benefit is Unlikely," Summary of and commentary on research findings, including GAIT.
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