Examine individual changes

'{{Chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464190859 | ImageFileL1 = Glucosamine Structural Formulae V.1.svg | ImageFileL1_Ref = {{Chemboximage|correct|??}} | ImageNameL1 = Stereo structural formula of glucosamine ((2S,6R)-6-meth,-2-ol) | ImageFileR1 = beta-D-glucosamine-3D-balls.png | ImageFileR1_Ref = {{Chemboximage|correct|??}} | ImageNameR1 = Ball and stick model of glucosamine ((2R,6R)-6-meth,-2-ol) | IUPACName = (3''R'',4''R'',5''S'')-3-Amino-6-(hydroxymethyl)oxane-2,4,5-triol | OtherNames = 2-Amino-2-deoxy-glucose<br /> Chitosamine |Section1={{Chembox Identifiers | CASNo = 3416-24-8 | CASNo_Ref = {{cascite|correct|CAS}} | PubChem = 439213 | ChemSpiderID = 388352 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | UNII = N08U5BOQ1K | UNII_Ref = {{fdacite|correct|FDA}} | EINECS = 222-311-2 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01296 | KEGG = D04334 | KEGG_Ref = {{keggcite|changed|kegg}} | MeSHName = Glucosamine | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 5417 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 181132 | Beilstein = 1723616 | Gmelin = 720725 | SMILES = N[C@H]1C(O)OC(CO)[C@@H](O)[C@@H]1O | StdInChI = 1S/C6H13NO5/c7-3-5(10)4(9)2(1-8)12-6(3)11/h2-6,8-11H,1,7H2/t2?,3-,4-,5-,6?/m1/s1 | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = MSWZFWKMSRAUBD-SPZCMYQFSA-N | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} }} |Section2={{Chembox Properties | C=6 | H=13 | N=1 | O=5 | MeltingPtC = 150 | LogP = -2.175 | Density = 1.563 g/mL | pKa = 12.273 | pKb = 1.724 }} |Section6={{Chembox Pharmacology | ATCCode_prefix = M01 | ATCCode_suffix = AX05 }} }} '''Glucosamine''' (C₆H₁₃NO₅) is an [[amino sugar]] and a prominent precursor in the [[biochemical]] synthesis of [[glycosylation|glycosylated]] proteins and lipids. Glucosamine is part of the structure of the [[polysaccharide]]s, [[chitosan]], and [[chitin]]. Glucosamine is one of the most abundant [[monosaccharide]]s.<ref name="carb"/> It is produced commercially by the [[hydrolysis]] of crustacean [[exoskeleton]]s or, less commonly, by fermentation of a grain such as corn or wheat. Evidence for the effectiveness of glucosamine as a [[dietary supplement]] is mixed. In the United States, it is one of the most common [[dietary supplement]]s used by adults that is neither a [[vitamin]] nor a [[mineral]].<ref>{{cite journal |url=http://nccam.nih.gov/news/2008/nhsr12.pdf |page=4 |first1=Patricia M. |last1=Barnes |first2=Barbara |last2=Bloom |first3=Richard L. |last3=Nahin |title=Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007 |journal=National Health Statistics Reports |number=12 |date=December 10, 2008 |access-date=March 1, 2018}}</ref> ==Medical uses== 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.<ref>Staff, FDA Last Updated April 11, 2013 [http://www.fda.gov/Food/DietarySupplements/QADietarySupplements/default.htm Q&A on Dietary Supplements]</ref> 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|''N''-acetylglucosamine]]. Of the three commonly available forms of glucosamine, only glucosamine sulfate is given a "likely effective" rating for treating osteoarthritis.<ref name="mlp">{{cite web|title=Glucosamine sulfate|url=https://www.nlm.nih.gov/medlineplus/druginfo/natural/807.html|publisher=MedlinePlus, US National Library of Medicine|date=22 April 2016}}</ref> Glucosamine is often sold in combination with other supplements such as [[chondroitin sulfate]] and [[methylsulfonylmethane]]. Glucosamine, along with commonly used [[chondroitin]], is not routinely prescribed to treat people who have symptomatic osteoarthritis of the knee, as there is insufficient evidence that this treatment is helpful.<ref name="AAOSfive">{{Citation |author1 = American Academy of Orthopaedic Surgeons |author1-link = American Academy of Orthopaedic Surgeons |date = February 2013 |title = Five Things Physicians and Patients Should Question |publisher = American Academy of Orthopaedic Surgeons |work = [[Choosing Wisely]]: an initiative of the [[ABIM Foundation]] |page = |url = http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-orthopaedic-surgeons/ |accessdate = 19 May 2013}}</ref> As is common with heavily promoted dietary supplements, the claimed benefits of glucosamine are based principally on clinical and laboratory studies. Clinical studies are divided, with some reporting relief from arthritic pain and stiffness, while higher quality studies report no benefit above placebo.<ref name="towheed">{{cite journal|pmid=15846645|year=2005|last1=Towheed|first1=T. E.|title=Glucosamine for osteoarthritis|journal=The Cochrane Database of Systematic Reviews|issue=2|pages=CD002946|last2=Maxwell|first2=L|last3=Anastassiades|first3=T. P.|last4=Shea|first4=B|last5=Houpt|first5=J|last6=Robinson|first6=V|last7=Hochberg|first7=M. C.|last8=Wells|first8=G|doi=10.1002/14651858.CD002946.pub2}}</ref> There is no evidence to date that consumption of glucosamine by sport participants will prevent or limit joint damage after injury.<ref>{{Cite journal | pmid = 16766503 | year = 2006 | last1 = Hespel | first1 = P | title = Dietary supplements for football | journal = Journal of Sports Sciences | volume = 24 | issue = 7 | pages = 749–61 | last2 = Maughan | first2 = R. J. | last3 = Greenhaff | first3 = P. L. | doi = 10.1080/02640410500482974 }}</ref> In a randomized placebo-controlled trial, glucosamine supplementation had no additional effect on any [[Physical medicine and rehabilitation|rehabilitation]] outcome when given to athletes after [[anterior cruciate ligament]] (ACL) reconstruction.<ref>{{cite journal | vauthors = Eraslan A, Ulkar B | title = Glucosamine supplementation after anterior cruciate ligament reconstruction in athletes: a randomized placebo-controlled trial | journal = Res. Sports Med. | volume = 23 | issue = 1 | pages = 14–26 | year = 2015 | pmid = 25630243 | doi = 10.1080/15438627.2014.975809 }}</ref> ==Adverse effects and drug interactions== One clinical study over three years showed that glucosamine in doses of 1500&nbsp;mg per day is safe to use.<ref>{{cite journal|title=Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial|journal=The Lancet|date=January 2011|volume=357|issue=9252|pages=251–256|url=http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)03610-2/fulltext|doi=10.1016/S0140-6736(00)03610-2|pmid=11214126|last1=Reginster|first1=Jean Yves|last2=Deroisy|first2=Rita|last3=Rovati|first3=Lucio C|last4=Lee|first4=Richard L|last5=Lejeune|first5=Eric|last6=Bruyere|first6=Olivier|last7=Giacovelli|first7=Giampaolo|last8=Henrotin|first8=Yves|last9=Dacre|first9=Jane E|last10=Gossett|first10=Christiane}}</ref> Glucosamine with or without chondroitin elevates the [[international normalized ratio]] (INR) in individuals who are taking the [[anticoagulant|blood thinner]], [[warfarin]].<ref name=mlp/><ref name = Pharmacotherapy>{{cite journal|title=Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database|journal=Pharmacotherapy|date=April 2008|pmid=18363538|doi=10.1592/phco.28.4.540|volume=28|issue=4|pages=540–8|last1=Knudsen|first1=J. F.|last2=Sokol|first2=G. H.|url=https://zenodo.org/record/1236349|type=Submitted manuscript}}</ref> It may also interfere with the efficacy of [[chemotherapy]] for treating [[cancer]] symptoms.<ref name=mlp/> Adverse effects may include stomach upset, constipation, diarrhea, headache, and rash.<ref name="ARC report">{{cite web|title=Complementary and alternative medicines for the treatment of rheumatoid arthritis, osteoarthritis and fibromyalgia|publisher=Arthritis Research UK|pages=34–5|url=http://www.arthritisresearchuk.org/~/media/Files/Arthritis-information/Additional-items/CAM%20Report.ashx?la=en|date=October 2012|accessdate=17 February 2017}}</ref> There are case reports of people who have chronic liver disease and a worsening of their condition with glucosamine supplementation.<ref>{{cite journal|title=Hepatotoxicity associated with glucosamine and chondroitin sulfate in patients with chronic liver disease|journal=World J. Gastroenterol.|date=Aug 28, 2013|pages=5381–5384|pmc=3752575|pmid=23983444|doi=10.3748/wjg.v19.i32.5381|volume=19|issue=32|last1=Cerda|first1=C|last2=Bruguera|first2=M|last3=Parés|first3=A}}</ref> More high-quality clinical research is needed before recommending glucosamine in pregnancy.<ref name=mlp/> Since glucosamine is usually derived from the shells of [[shellfish]], it may be unsafe for those with [[shellfish allergy]].<ref>{{cite journal |author1=Gray HC|author2=Hutcheson PS|author3=Slavin RG |title=Is glucosamine safe in patients with seafood allergy? |journal=[[The Journal of Allergy and Clinical Immunology]] |volume=114 |issue=2 |pages=459–60 |date=August 2004 |pmid=15341031 |doi= 10.1016/j.jaci.2004.05.050}}</ref> 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.<ref>{{cite web |url=http://dietarysupplements.nlm.nih.gov/dietary/detail.jsp?name=Kirkland+Signature+Extra+Strength+Glucosamine+with+MSM&contain=11001019&pageD=brand |archiveurl=https://web.archive.org/web/20100304095044/http://dietarysupplements.nlm.nih.gov/dietary/detail.jsp?contain=11001019&name=Kirkland+Signature+Extra+Strength+Glucosamine+with+MSM&pageD=brand |archivedate=4 March 2010 |accessdate=23 April 2015 |title=Kirkland Signature Extra Strength Glucosamine with MSM |date=3 February 2010 |work=Dietary Supplements Labels Database |publisher=U.S. National Library of Medicine}}</ref> Alternative, non-shellfish-derived forms of glucosamine are available.<ref name=VegSources2008>{{cite web|url=http://www.nutraingredients-usa.com/Industry/Another-vegetarian-glucosamine-launched-in-US |title=Another vegetarian glucosamine launched in US |date=January 25, 2008|work=NutraIngredients-USA.com |archiveurl=https://web.archive.org/web/20090417035225/http://www.nutraingredients-usa.com/Industry/Another-vegetarian-glucosamine-launched-in-US |archive-date=April 17, 2009 |deadurl=yes |df= }}</ref> Another concern has been that the extra glucosamine could contribute to diabetes by interfering with the normal regulation of the [[hexosamine]] biosynthesis pathway,<ref name="Buse"/> but several investigations found no evidence that this occurs.<ref>{{cite journal |author1=Scroggie DA|author2=Albright A|author3=Harris MD |title=The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial |journal=[[Archives of Internal Medicine]] |volume=163 |issue=13 |pages=1587–90 |date=July 2003 |pmid=12860582 |doi=10.1001/archinte.163.13.1587}}</ref><ref>{{cite journal |author1=Tannis AJ|author2=Barban J|author3=Conquer JA |title=Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals |journal=[[Osteoarthritis and Cartilage]] |volume=12 |issue=6 |pages=506–11 |date=June 2004 |pmid=15135147 |doi=10.1016/j.joca.2004.03.001}}</ref> Other studies conducted in lean or obese subjects concluded that oral glucosamine at standard doses does not affect [[insulin resistance]].<ref>{{cite journal |author=Muniyappa R |title=Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects |journal=[[Diabetes (journal)|Diabetes]] |volume=55 |issue=11 |pages=3142–50 |date=November 2006 |pmid=17065354 |doi=10.2337/db06-0714 |author2=Karne RJ |author3=Hall G |display-authors=3 |last4=Crandon |first4=S. K. |last5=Bronstein |first5=J. A. |last6=Ver |first6=M. R. |last7=Hortin |first7=G. L. |last8=Quon |first8=M. J. }}</ref><ref>{{cite journal |author1=Biggee BA|author2=Blinn CM|author3=Nuite M|author4=Silbert JE|author5=McAlindon TE |title=Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis |journal=[[Annals of the Rheumatic Diseases]] |volume=66 |issue=2 |pages=260–2 |date=February 2007 |pmid=16818461 |pmc=1798503 |doi=10.1136/ard.2006.058222}}</ref> ==Biochemistry== Glucosamine is naturally present in the shells of shellfish, animal bones, bone marrow, and fungi.<ref>{{cite journal |title=Scientific Opinion of the Panel on Dietetic Products Nutrition and Allergies on a request from the European Commission on the safety of glucosamine hydrochloride from ''Aspergillus niger'' as food ingredient |journal=The EFSA Journal |volume=1099 |pages=1–19 |year=2009 |url=http://www.efsa.europa.eu/en/efsajournal/pub/1099}}</ref> D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all [[amino sugar|nitrogen-containing sugars]].<ref>{{cite journal | author = Roseman S | title = Reflections on glycobiology | journal = [[J Biol Chem]] | year = 2001 | volume = 276 | issue = 45 | pages = 41527–42 | pmid = 11553646 | doi = 10.1074/jbc.R100053200 | format = free full text}}</ref> Specifically in humans, glucosamine-6-phosphate is synthesized from [[fructose 6-phosphate]] and [[glutamine]] by [[Glutamine—fructose-6-phosphate transaminase (isomerizing)|glutamine—fructose-6-phosphate transaminase]]<ref>[[Glutamine—fructose-6-phosphate transaminase (isomerizing)]]</ref> as the first step of the hexosamine biosynthesis pathway.<ref>{{cite web |url=http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/polysacc/UDPGlcN.html |publisher=International Union of Biochemistry and Molecular Biology |title=UDP-N-acetylglucosamine Biosynthesis |work=Recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology on the Nomenclature and Classification of Enzymes by the Reactions they Catalyse |year=2002 |accessdate=2012-09-10 }}</ref> The end-product of this pathway is [[uridine diphosphate N-acetylglucosamine]] (UDP-GlcNAc), which is then used for making [[glycosaminoglycan]]s, [[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.<ref name="Buse">{{cite journal | author = Buse MG | title = Hexosamines, insulin resistance, and the complications of diabetes: current status | journal = [[Am. J. Physiol. Endocrinol. Metab.]] | year = 2006 | volume = 290 | issue = 1 | pages = E1–E8 | pmid = 16339923 | doi = 10.1152/ajpendo.00329.2005 | pmc = 1343508}}</ref> ==Manufacturing== Most glucosamine is manufactured by processing [[chitin]] from the shells of [[shellfish]] including shrimp, lobsters, and crabs.<ref>{{cite book|last1=Murray|first1=Michael T.|editor1-last=Pizzorno, Jr.|editor1-first=Joseph E.|editor2-last=Murray|editor2-first=Michael T.|title=Textbook of natural medicine|date=2012|publisher=Churchill Livingstone|location=Edinburgh|isbn=9781437723335|page=790|edition=4th|chapter-url=https://books.google.com/books?id=6cjgo1IixvEC&pg=PA790|chapter=Chapter 94: Glucosamine}}</ref> To meet the demands of vegetarians and others with objections to shellfish, manufacturers have brought glucosamine products to market made using fungus ''[[Aspergillus niger]]'' and from fermenting corn.<ref name=VegSources2008/> ==History== Glucosamine was first prepared in 1876 by [[Georg Ledderhose]] by the [[hydrolysis]] of [[chitin]] with concentrated [[hydrochloric acid]].<ref>{{cite journal|author=Georg Ledderhose |year=1876 |url=https://books.google.com/books?id=hltBAAAAYAAJ&pg=PA1200#v=onepage&q&f=false |title=Über salzsaures Glycosamin |trans-title=On glucosamine hydrochloride |journal=Berichte der Deutschen Chemischen Gesellschaft |volume=9 |issue=2 |pages=1200–1201|doi=10.1002/cber.18760090251}}</ref><ref>{{cite journal |author = Ledderhose G |authorlink =Georg Ledderhose|year = 1879|journal = Zeitschrift für Physiologische Chemie |title = Über Chitin und seine Spaltungs-produkte |trans-title=On chitin and its hydrolysis products |volume = ii |pages = 213–227 }}</ref><ref>{{cite journal |author = Ledderhose G |authorlink = Georg Ledderhose|year = 1880 |journal = Zeitschrift für Physiologische Chemie|title = Über Glykosamin|volume = iv |pages = 139–159}}</ref> The [[stereochemistry]] was not fully determined until the 1939 work of [[Walter Haworth]].<ref name="carb">{{cite book |vauthors=Pigman WW, Horton D, Wander JD | title =The Carbohydrates | volume =Vol IB | publisher =Academic Press | year =1980 | location =New York | pages =727–728 | isbn =9780125563512 }}</ref><ref>{{cite journal|author1=W. N. Haworth|author2=W. H. G. Lake|author3=S. Peat |year=1939 |title=The configuration of glucosamine (chitosamine) |journal=Journal of the Chemical Society |pages=271–274|doi=10.1039/jr9390000271}}</ref> == Legal status == === United States === In the United States, glucosamine is not approved by the [[Food and Drug Administration]] for medical use in humans.<ref name="FDA2004">{{cite web|url=http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm073400.htm|title=Letter Regarding the Relationship Between the Consumption of Glucosamine and/or Chondroitin Sulfate and a Reduced Risk of: Osteoarthritis; Osteoarthritis-related Joint Pain, Joint Tenderness, and Joint Swelling; Joint Degeneration; and Cartilage Deterioration(Docket No. 2004P-0059)|author=Hubbard WK, Associate Commissioner of Policy and Planning|year=2012|publisher=United States Department of Health and Human Services, Food and Drug Administration|accessdate=14 May 2014|quote=FDA concludes that there is no credible evidence to support qualified health claims for glucosamine or chondroitin sulfate and reduced risk of osteoarthritis, joint degeneration or cartilage deterioration.}}</ref> Since glucosamine is classified as a [[dietary supplement]] in the US, evidence of safety is required by FDA regulations, but evidence of efficacy is not required so long as it is not advertised as a treatment for a medical condition.<ref>{{cite web|url=http://www.cfsan.fda.gov/~dms/supplmnt.html |title=Dietary Supplements |publisher=[[U.S. Food and Drug Administration]] |accessdate=December 10, 2009}}</ref> === Europe === In most of Europe, glucosamine is approved as a medical drug and is sold in the form of glucosamine sulfate.<ref name="EULAR" /> 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,<ref name="EULAR">{{cite journal |author=Jordan KM |title=EULAR Recommendations 2003: a evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT) |journal=[[Annals of the Rheumatic Diseases]] |volume=62 |issue=12 |pages=1145–55 |date=December 2003 |pmid=14644851 |pmc=1754382 |doi= 10.1136/ard.2003.011742 |author2=Arden NK |author3=Doherty M |display-authors=3 |last4=Bannwarth |first4=B |last5=Bijlsma |first5=JW |last6=Dieppe |first6=P |last7=Gunther |first7=K |last8=Hauselmann |first8=H |last9=Herrero-Beaumont |first9=G |first14=B |first15=E |first16=K |first17=A |first18=L |first19=U |first20=B |first21=G}}</ref> and recent OARSI (OsteoArthritis Research Society International) guidelines for hip and knee osteoarthritis indicate an acceptable safety profile.<ref>{{cite journal |author=Zhang W |title=OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence |journal=[[Osteoarthritis and Cartilage]] |volume=15 |issue=9 |pages=981–1000 |date=September 2007 |pmid=17719803 |doi=10.1016/j.joca.2007.06.014 |author2=Moskowitz RW |author3=Nuki G |display-authors=3 |last4=Abramson |first4=S |last5=Altman |first5=R |last6=Arden |first6=N |last7=Biermazeinstra |first7=S |last8=Brandt |first8=K |last9=Croft |first9=P |first14=K. |first15=L.S. |first16=P.}}</ref> By 2014, the OARSI did not recommend glucosamine for disease modification, and considered it "uncertain" for symptom relief, in knee osteoarthritis.<ref>{{cite journal|journal=Osteoarthritis and Cartilage|date=March 2014 |volume=22 |issue=3 |pages=363–88 |title=OARSI guidelines for the non-surgical management of knee osteoarthritis |author1=McAlindon TE|author2=Bannuru RR|author3=Sullivan MC|author4=Arden NK|author5=Berenbaum F|author6=Bierma-Zeinstra SM|author7=Hawker GA|author8=Henrotin Y|author9=Hunter DJ|author10=Kawaguchi H|author11=Kwoh K|author12=Lohmander S|author13=Rannou F|author14=Roos EM|author15=Underwood M |pmid=24462672 |doi=10.1016/j.joca.2014.01.003 }}</ref> === Class action lawsuits === 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.<ref>{{cite web|url= http://glucosaminesettlement.com/ |title=Glucosamine Settlement |publisher=www.glucosaminesettlement.com |accessdate=June 17, 2013}}</ref> In August 2012, a class action lawsuit was filed in New York claiming that 21st Century Healthcare, Inc. had falsely advertised that its “Glucosamine 750 Chondroitin 600 Triple Strength” dietary supplements would restore lost cartilage.<ref>{{cite web|url=http://www.topclassactions.com/lawsuit-settlements/lawsuit-news/2452-21st-century-glucosaminechondroitin-triple-strength-class-action-lawsuit# |title=21st Century Glucosamine/Chondroitin Triple Strength Class Action Lawsuit |publisher=www.topclassactions.com |accessdate=June 17, 2013|date=2012-09-14 }}</ref> 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.<ref>{{cite web|url=http://www.law360.com/articles/432329/wal-mart-rite-aid-face-suit-over-glucosamine-promises |title=Wal-Mart, Rite Aid Face Suit Over Glucosamine Promises|publisher=www.law360.com |accessdate=June 17, 2013}}</ref> ==Research== ===Humans=== {{main|Clinical trials on glucosamine and chondroitin}} Since glucosamine is a precursor for [[glycosaminoglycan]]s, and glycosaminoglycans are a major component of [[cartilage]], research has focused on the potential for supplemental glucosamine to beneficially influence cartilage structure and alleviate [[arthritis]]. Although its use as a supplement appears safe, the evidence does not support it being universally effective, as [[clinical trial]]s have not provided results that support its efficacy in 100% of human subjects.<ref name=AAOSfive/><ref name=towheed/> ====Bioavailability==== Two studies measured the concentrations of glucosamine in the [[synovial fluid]] and [[Blood plasma|plasma]] after oral administration of glucosamine sulfate to both healthy volunteers and people with osteoarthritis.<ref>{{cite journal |author=Persiani S |title=Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulphate at therapeutic dose |journal=[[Osteoarthritis and Cartilage]] |volume=15 |issue=7 |pages=764–72 |date=July 2007 |pmid=17353133 |doi=10.1016/j.joca.2007.01.019 |author2=Rotini R |author3=Trisolino G |display-authors=3 |last4=Rovati |first4=L.C. |last5=Locatelli |first5=M. |last6=Paganini |first6=D. |last7=Antonioli |first7=D. |last8=Roda |first8=A.}}</ref><ref>{{cite journal |author1=Persiani S|author2=Roda E|author3=Rovati LC|author4=Locatelli M|author5=Giacovelli G|author6=Roda A |title=Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man |journal=[[Osteoarthritis and Cartilage]] |volume=13 |issue=12 |pages=1041–9 |date=December 2005 |pmid=16168682 |doi=10.1016/j.joca.2005.07.009}}</ref> In the first study, glucosamine sulfate was given to healthy volunteers in doses of 750, 1500 or 3000&nbsp;mg once daily. In the second study, oral glucosamine sulfate capsules (1500&nbsp;mg) were given daily for two weeks to 12 people with [[osteoarthritis]]. Glucosamine concentrations in plasma and [[synovial fluid]] increased significantly from baseline levels and the levels in the two fluids were highly correlated. The authors interpreted that these levels could be biologically advantageous to [[articular cartilage]], but the levels are still 10 - 100 fold lower than required to positively affect the [[cartilage]] ([[chondrocytes]]) to build new tissue.<ref>{{Cite journal | pmid = 15529373 | year = 2004 | last1 = Mroz | first1 = P. J. | title = Use of 3H-glucosamine and 35S-sulfate with cultured human chondrocytes to determine the effect of glucosamine concentration on formation of chondroitin sulfate | journal = Arthritis & Rheumatism | volume = 50 | issue = 11 | pages = 3574–9 | last2 = Silbert | first2 = J. E. | doi = 10.1002/art.20609 }}</ref> Glucosamine sulfate uptake in [[synovial fluid]] may be as much as 20%, or could be negligible, indicating no biological significance.<ref>{{cite book |vauthors=Cohen MJ, Braun L |title=Herbs & natural supplements: an evidence-based guide |publisher=Elsevier Australia |location=Marrickville, New South Wales |year=2007 |isbn=978-0-7295-3796-4 }}</ref> ==Veterinary medicine== <!--needs secondary sources - try PMID 21733414 instead of some of these --> {{expand section|date=December 2013}} Some studies have shown efficacy of glucosamine supplementation for dogs with osteoarthritis pain, particularly in combination with other nutraceuticals like chondroitin<ref>{{Cite journal | pmid = 21623931 | year = 2012 | last1 = Gupta | first1 = R. C. | title = Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: Pain evaluation by ground force plate | journal = Journal of Animal Physiology and Animal Nutrition | volume = 96 | issue = 5 | pages = 770–7 | last2 = Canerdy | first2 = T. D. | last3 = Lindley | first3 = J | last4 = Konemann | first4 = M | last5 = Minniear | first5 = J | last6 = Carroll | first6 = B. A. | last7 = Hendrick | first7 = C | last8 = Goad | first8 = J. T. | last9 = Rohde | first9 = K | last10 = Doss | first10 = R | last11 = Bagchi | first11 = M | last12 = Bagchi | first12 = D | doi = 10.1111/j.1439-0396.2011.01166.x }}</ref><ref>{{Cite journal | pmid = 20020968 | year = 2007 | last1 = d'Altilio | first1 = M | title = Therapeutic Efficacy and Safety of Undenatured Type II Collagen Singly or in Combination with Glucosamine and Chondroitin in Arthritic Dogs | journal = Toxicology Mechanisms and Methods | volume = 17 | issue = 4 | pages = 189–96 | last2 = Peal | first2 = A | last3 = Alvey | first3 = M | last4 = Simms | first4 = C | last5 = Curtsinger | first5 = A | last6 = Gupta | first6 = R. C. | last7 = Canerdy | first7 = T. D. | last8 = Goad | first8 = J. T. | last9 = Bagchi | first9 = M | last10 = Bagchi | first10 = D | doi = 10.1080/15376510600910469 }}</ref> while others have not.<ref name="Moreau">Ā{{Cite journal | pmid = 12665145 | year = 2003 | last1 = Moreau | first1 = M | title = Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis | journal = The Veterinary Record | volume = 152 | issue = 11 | pages = 323–9 | last2 = Dupuis | first2 = J | last3 = Bonneau | first3 = N. H. | last4 = Desnoyers | first4 = M | doi=10.1136/vr.152.11.323 }}</ref> 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.<ref name=Moreau/> 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.<ref>{{cite journal|pmid=19927591|year=2009|last1=Pearson|first1=W|last2=Lindinger|first2=M|title=Low quality of evidence for glucosamine-based nutraceuticals in equine joint disease: Review of in vivo studies|volume=41|issue=7|pages=706–12|journal=Equine Veterinary Journal |doi=10.2746/042516409X424153}}</ref> A number of studies have measured the bioavailability of glucosamine after oral administration to horses. When given as a single oral dose (nine grams) with or without [[chondroitin sulfate]] (three grams) to ten horses, glucosamine (hydrochloride) was detected in the blood with a maximum level of 10.6 (+/- 6.9) micrograms per millilitre at two hours after dosing.<ref>{{Cite journal | pmid = 15083499 | year = 2004 | last1 = Du | first1 = J | title = The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse | journal = Biopharmaceutics & Drug Disposition | volume = 25 | issue = 3 | pages = 109–16 | last2 = White | first2 = N | last3 = Eddington | first3 = N. D. | doi = 10.1002/bdd.392 }}</ref> Another study examined both the serum and the joint [[synovial fluid]] after nasogastric (oral) or intravenous administration of 20&nbsp;mg/kg glucosamine hydrochloride to eight adult horses.<ref>{{Cite journal | pmid = 15641100 | year = 2005 | last1 = Laverty | first1 = S | title = Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses | journal = Arthritis and Rheumatism | volume = 52 | issue = 1 | pages = 181–91 | last2 = Sandy | first2 = J. D. | last3 = Celeste | first3 = C | last4 = Vachon | first4 = P | last5 = Marier | first5 = J. F. | last6 = Plaas | first6 = A. H. | doi = 10.1002/art.20762 }}</ref> Although joint fluid concentrations of glucosamine reached 9 - 15 micromolar following intravenous dosing, it was only 0.3 - 0.7 micromolar with nasogastric dosing. The authors calculated that these glucosamine synovial fluid levels achieved by the oral route were 500 fold lower than that required to have a positive effect on the metabolism of [[cartilage]] cells. A follow up study by the same research group compared glucosamine sulfate with glucosamine hydrochloride at the same dose (20&nbsp;mg/kg) in eight horses and found a higher fluid concentration with the sulfate preparation (158&nbsp;ng/mL compared to 89&nbsp;ng/mL one hour post oral dose).<ref>{{Cite journal | pmid = 18295513 | year = 2008 | last1 = Meulyzer | first1 = M | title = Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride | journal = Osteoarthritis and Cartilage | volume = 16 | issue = 9 | pages = 973–9 | last2 = Vachon | first2 = P | last3 = Beaudry | first3 = F | last4 = Vinardell | first4 = T | last5 = Richard | first5 = H | last6 = Beauchamp | first6 = G | last7 = Laverty | first7 = S | doi = 10.1016/j.joca.2008.01.006 }}</ref> They concluded that these higher [[synovial fluid]] levels obtained with the sulfate derivative were still too low to have a relevant biological effect on [[articular cartilage]]. A three-month trial of an oral dosage regime of a commercial preparation of glucosamine sulfate, chondroitin sulfate and [[methylsulfonylmethane]] was performed in veteran horses with no effect on gait stiffness, with exercise alone in the control group being effective.<ref>{{Cite journal | pmid = 24011144 | year = 2013 | last1 = Higler | first1 = M. H. | title = The effects of three-month oral supplementation with a nutraceutical and exercise on the locomotor pattern of aged horses | journal = Equine Veterinary Journal | last2 = Brommer | first2 = H | last3 = l'Ami | first3 = J. J. | last4 = De Grauw | first4 = J. C. | last5 = Nielen | first5 = M | last6 = Van Weeren | first6 = P. R. | last7 = Laverty | first7 = S | last8 = Barneveld | first8 = A | last9 = Back | first9 = W | doi = 10.1111/evj.12182 | volume=46 | issue = 5 | pages=611–7 }}</ref> The intravenous use of a combination of N-acetylglucosamine, 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,<ref>{{Cite journal | pmid = 24819506 | year = 2014 | last1 = Koenig | first1 = T. J. | title = Treatment of Experimentally Induced Osteoarthritis in Horses Using an Intravenous Combination of Sodium Pentosan Polysulfate, N-Acetyl Glucosamine, and Sodium Hyaluronan | journal = Veterinary Surgery | pages = 612–22 | last2 = Dart | first2 = A. J. | last3 = McIlwraith | first3 = C. W. | last4 = Horadagoda | first4 = N | last5 = Bell | first5 = R. J. | last6 = Perkins | first6 = N | last7 = Dart | first7 = C | last8 = Krockenberger | first8 = M | last9 = Jeffcott | first9 = L. B. | last10 = Little | first10 = C. B. | doi = 10.1111/j.1532-950X.2014.12203.x | volume=43 | issue=5 }}</ref> suggesting more evidence is needed for this combination and route of administration. ==See also== * [[Chitobiose]] * [[Chitosan]] * [[Chondroitin sulfate]] * [[Methylsulfonylmethane]] ==References== {{Reflist|colwidth=30em}} ==External links== *[http://www.mayoclinic.com/health/glucosamine/NS_patient-glucosamine Glucosamine article, Mayo Clinic] *[http://www.arthritis.org/living-with-arthritis/treatments/natural/supplements-herbs/glucosamine-chondroitin-osteoarthritis.php General glucosamine and chondroitin sulfate information, Arthritis Foundation] {{Dietary supplement}} {{Anti-inflammatory and antirheumatic products}} [[Category:Hexosamines]] [[Category:Dietary supplements]]'