Glucosamine

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Glucosamine
Stereo structural formula of glucosamine ((2S,6R)-6-meth,-2-ol) Ball and stick model of glucosamine ((2R,6R)-6-meth,-2-ol)
Identifiers
CAS number 3416-24-8 YesY
PubChem 439213
ChemSpider 388352 N
UNII N08U5BOQ1K YesY
EC number 222-311-2
DrugBank DB01296
KEGG D04334 N
MeSH Glucosamine
ChEBI CHEBI:5417 N
ChEMBL CHEMBL181132 N
ATC code M01AX05
Beilstein Reference 1723616
Gmelin Reference 720725
Jmol-3D images Image 1
Properties
Molecular formula C6H13NO5
Molar mass 179.17 g mol−1
Density 1.563 g/mL
Melting point 150 °C (302 °F; 423 K)
log P -2.175
Acidity (pKa) 12.273
Basicity (pKb) 1.724
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

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, as well as the cell walls of fungi and many higher organisms. Glucosamine is one of the most abundant monosaccharides.[1] It is produced commercially by the hydrolysis of crustacean exoskeletons or, less commonly, by fermentation of a grain such as corn or wheat.[2] In the US it is one of the most common non-vitamin, non-mineral, dietary supplements used by adults.[3]

Medical uses[edit]

Oral glucosamine is a dietary supplement and is not a pharmaceutical drug. It is illegal in the US to market any dietary supplement as a treatment for any disease or condition.[4] Glucosamine is marketed to support the structure and function of joints and the marketing is targeted to people suffering from osteoarthritis. Commonly sold forms of glucosamine are glucosamine sulfate, glucosamine hydrochloride, and N-acetylglucosamine. Glucosamine is often sold in combination with other supplements such as chondroitin sulfate and methylsulfonylmethane. Of the three commonly available forms of glucosamine, only glucosamine sulfate is given a "likely effective" rating for treating osteoarthritis.[5]

Glucosamine, along with commonly used condroitin, should not be used to treat patients who have symptomatic osteoarthritis of the knee as evidence shows that these treatments fail to provide relief for that condition.[6]

Adverse effects[edit]

Clinical studies have consistently reported that glucosamine appears safe.[citation needed] However, a recent Université Laval study shows that people taking glucosamine tend to go beyond recommended guidelines, as they do not feel any positive effects from the dietary supplement. Beyond recommended dosages, researchers found in preliminary studies that glucosamine may damage pancreatic cells, possibly increasing the risk of developing diabetes.[7]

Adverse effects, which are usually mild and infrequent, include stomach upset, constipation, diarrhea, headache and rash.[8]

Since glucosamine is usually derived from the shells of shellfish while the allergen is within the flesh of the animals, it is probably safe even for those with shellfish allergy.[9] However, many manufacturers of glucosamine derived from shellfish include a warning that those with a seafood allergy should consult a healthcare professional before taking the product.[10][11] Alternative, non-shellfish derived forms of glucosamine are available.[12]

Another concern has been that the extra glucosamine could contribute to diabetes by interfering with the normal regulation of the hexosamine biosynthesis pathway,[13] but several investigations have found no evidence that this occurs.[14][15][16] A manufacturer-supported review conducted by Anderson et al. in 2005 summarizes the effects of glucosamine on glucose metabolism in in vitro studies, the effects of oral administration of large doses of glucosamine in animals, and the effects of glucosamine supplementation with normal recommended dosages in humans, concluding that glucosamine does not cause glucose intolerance and has no documented effects on glucose metabolism.[17] Other studies conducted in lean or obese subjects concluded that oral glucosamine at standard doses does not cause or significantly worsen insulin resistance or endothelial dysfunction.[18][19][20]

Biochemistry[edit]

Glucosamine is naturally present in the shells of shellfish, animal bones, bone marrow, and fungi.[21]

History[edit]

Glucosamine was first prepared in 1876 by Georg Ledderhose by the hydrolysis of chitin with concentrated hydrochloric acid.[22][23][24] The stereochemistry was not fully determined until the 1939 work of Walter Haworth.[1][25] D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all nitrogen-containing sugars.[26] Specifically, glucosamine-6-phosphate is synthesized from fructose 6-phosphate and glutamine by glucosamine-6-phosphate deaminase[27] as the first step of the hexosamine biosynthesis pathway.[28] The end-product of this pathway is Uridine diphosphate 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.[13]

Legal status[edit]

United States[edit]

In the United States, glucosamine is not approved by the Food and Drug Administration for medical use in humans.[29] Since glucosamine is classified as a dietary supplement in the US, safety and formulation are solely the responsibility of the manufacturer; evidence of safety and efficacy is not required as long as it is not advertised as a treatment for a medical condition.[30] 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.[31]

Europe[edit]

In most of Europe, glucosamine is approved as a medical drug and is sold in the form of glucosamine sulfate.[32] In this case, evidence of safety and efficacy is required for the medical use of glucosamine and several guidelines have recommended its use as an effective and safe therapy for osteoarthritis. The Task Force of the European League Against Rheumatism (EULAR) committee has granted glucosamine sulfate a level of toxicity of 5 in a 0-100 scale,[32] and recent OARSI (OsteoArthritis Research Society International) guidelines for hip and knee osteoarthritis indicate an acceptable safety profile.[33]

Class action lawsuits[edit]

In 2013, without admitting fault, manufacturer Rexall Sundown, Inc., and NBTY, Inc., agreed to pay up to $2 million to settle consumer claims related to the wording of certain claims on the packaging of glucosamine bottles sold at Costco under the Kirkland label.[34]

In August 2012, a class action lawsuit was filed in New York claiming that 21st Century Healthcare, Inc. falsely advertises that its “Glucosamine 750 Chondroitin 600 Triple Strength” dietary supplements will restore lost cartilage.[35] In April 2013, a San Diego man launched a proposed class action lawsuit in California Federal Court accusing Nutramax Laboratories, Walmart and Rite Aid of falsely advertising the effectiveness of glucosamine.[36] The two class actions are still pending.

Research[edit]

Clinical trials on glucosamine and chondroitin[edit]

Since glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of cartilage, some have hoped that supplemental glucosamine could beneficially influence cartilage structure, and alleviate arthritis. Its use as a therapy for osteoarthritis appears safe, but there is no unequivocal evidence for its effectiveness. There have been multiple clinical trials testing glucosamine as a potential medical therapy for osteoarthritis, but the results have not supported its use.

Possibility of bioavailability[edit]

Recent studies provide preliminary evidence that glucosamine may be bioavailable in the synovial fluid after oral administration of crystalline glucosamine sulfate in osteoarthritis patients, as steady state glucosamine concentrations in plasma and synovial fluid were correlated.[37][38] If eventually proven, glucosamine sulfate uptake in synovial fluid may be as much as 20%, or as little as a negligible amount, indicating no biological significance.[39]

Veterinary medicine[edit]

Some studies have shown efficacy of glucosamine supplementation for dogs with osteoarthritis pain, particularly in combination with other nutraceuticals like chondroitin[40][41] while others have not.[42] A trial of oral combination capsules (glucosamine/chondroitin/manganese ascorbate) in dogs with osteoarthritis found no benefit on either gait analysis or subjective assessments by the veterinarian or owner.[42]

The use of glucosamine in equine medicine exists, but one meta-analysis judged extant research too flawed to be of value in guiding treatment of horses.[43] The intravenous use of a combination of N-acetylglucosime, pentosan polysulfate and sodium hyaluronate in horses with surgically-induced osteoarthritis saw improvements in xray changes to the cartilage but not histologically or in biochemical outcomes,[44] suggesting more evidence is needed for this combination and route of administration.

See also[edit]

References[edit]

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  4. ^ Staff, FDA Last Updated April 11, 2013 Q&A on Dietary Supplements
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  6. ^ American Academy of Orthopaedic Surgeons (February 2013), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation (American Academy of Orthopaedic Surgeons), retrieved 19 May 2013 , which cites
    • Jevsevar, DS; Brown, GA; Jones, DL; Matzkin, EG; Manner, PA; Mooar, P; Schousboe, JT; Stovitz, S; Sanders, JO; Bozic, KJ; Goldberg, MJ; Martin WR, 3rd; Cummins, DS; Donnelly, P; Woznica, A; Gross, L; American Academy of Orthopaedic, Surgeons (Oct 16, 2013). "The American Academy of Orthopaedic Surgeons evidence-based guideline on: treatment of osteoarthritis of the knee, 2nd edition.". The Journal of bone and joint surgery. American volume 95 (20): 1885–6. PMID 24288804. 
    • Clegg, Daniel O.; Reda, Domenic J.; Harris, Crystal L.; Klein, Marguerite A.; O'Dell, James R.; Hooper, Michele M.; Bradley, John D.; Bingham, Clifton O.; Weisman, Michael H.; Jackson, Christopher G.; Lane, Nancy E.; Cush, John J.; Moreland, Larry W.; Schumacher, H. Ralph; Oddis, Chester V.; Wolfe, Frederick; Molitor, Jerry A.; Yocum, David E.; Schnitzer, Thomas J.; Furst, Daniel E.; Sawitzke, Allen D.; Shi, Helen; Brandt, Kenneth D.; Moskowitz, Roland W.; Williams, H. James (23 February 2006). "Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis". New England Journal of Medicine 354 (8): 795–808. doi:10.1056/NEJMoa052771. 
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  10. ^ http://dietarysupplements.nlm.nih.gov/dietary/detail.jsp?name=Kirkland+Signature+Extra+Strength+Glucosamine+with+MSM&contain=11001019&pageD=brand
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  34. ^ "Glucosamine Settlement". www.glucosaminesettlement.com. Retrieved June 17, 2013. 
  35. ^ "21st Century Glucosamine/Chondroitin Triple Strength Class Action Lawsuit". www.topclassactions.com. Retrieved June 17, 2013. 
  36. ^ "Wal-Mart, Rite Aid Face Suit Over Glucosamine Promises". www.law360.com. Retrieved June 17, 2013. 
  37. ^ Persiani S, Roda E, Rovati LC, Locatelli M, Giacovelli G, Roda A (December 2005). "Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man". Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society 13 (12): 1041–9. doi:10.1016/j.joca.2005.07.009. PMID 16168682. 
  38. ^ Persiani S, Rotini R, Trisolino G et al. (July 2007). "Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulphate at therapeutic dose". Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society 15 (7): 764–72. doi:10.1016/j.joca.2007.01.019. PMID 17353133. 
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  40. ^ Gupta, R. C.; Canerdy, T. D.; Lindley, J; Konemann, M; Minniear, J; Carroll, B. A.; Hendrick, C; Goad, J. T.; Rohde, K; Doss, R; Bagchi, M; Bagchi, D (2012). "Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: Pain evaluation by ground force plate". Journal of Animal Physiology and Animal Nutrition 96 (5): 770–7. doi:10.1111/j.1439-0396.2011.01166.x. PMID 21623931.  edit
  41. ^ d'Altilio, M; Peal, A; Alvey, M; Simms, C; Curtsinger, A; Gupta, R. C.; Canerdy, T. D.; Goad, J. T.; Bagchi, M; Bagchi, D (2007). "Therapeutic Efficacy and Safety of Undenatured Type II Collagen Singly or in Combination with Glucosamine and Chondroitin in Arthritic Dogs". Toxicology Mechanisms and Methods 17 (4): 189–96. doi:10.1080/15376510600910469. PMID 20020968.  edit
  42. ^ a b ĀMoreau, M; Dupuis, J; Bonneau, N. H.; Desnoyers, M (2003). "Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis". The Veterinary record 152 (11): 323–9. PMID 12665145.  edit
  43. ^ Pearson, W; Lindinger, M (2009). "Low quality of evidence for glucosamine-based nutraceuticals in equine joint disease: Review of in vivo studies". Equine veterinary journal 41 (7): 706–12. doi:10.2746/042516409X424153. PMID 19927591. 
  44. ^ Koenig, T. J.; Dart, A. J.; McIlwraith, C. W.; Horadagoda, N; Bell, R. J.; Perkins, N; Dart, C; Krockenberger, M; Jeffcott, L. B.; Little, C. B. (2014). "Treatment of Experimentally Induced Osteoarthritis in Horses Using an Intravenous Combination of Sodium Pentosan Polysulfate, N-Acetyl Glucosamine, and Sodium Hyaluronan". Veterinary Surgery: n/a. doi:10.1111/j.1532-950X.2014.12203.x. PMID 24819506.  edit

External links[edit]