Glucosamine

Biochemistry

Glucosamine was first prepared in 1876 by Dr. 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.

Indications

Oral glucosamine is marketed as a treatment of osteoarthritis. Commonly sold forms of glucosamine are glucosamine sulfate and glucosamine hydrochloride. Glucosamine is often sold in combination with other supplements such as chondroitin sulfate and methylsulfonylmethane.

Glucosamine may take weeks to months before improvements in symptoms are noticed.

Restoration of cartilage

A 2009 review concluded that “Little evidence suggests that glucosamine is superior to a placebo treatment in restoring articular cartilage.”

Osteoarthritis pain

A 2009 scientific review of available studies concluded that glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate have individually shown inconsistent efficacy in decreasing OA pain, but many studies confirmed OA pain relief with glucosamine and chondroitin sulfate in combined use.

Health effects

Since glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, supplemental glucosamine may help to prevent cartilage degeneration and treat arthritis. Its use as a therapy for osteoarthritis appears safe, but there is conflicting evidence as to its effectiveness. A Cochrane 2005 meta-analysis of glucosamine for osteoarthritis found that only “Rotta” preparations (including older studies) found beneficial effects for pain and functional impairment. It also found that when only the studies using the highest-quality design were considered, there was no effect above placebo. In addition, in vitro analysis of glucosamine has revealed that glucosamine inhibits cartilage cell characteristics. Studies reporting beneficial effects have generally used glucosamine sulfate. Chondroitin sulfate is sometimes used in conjunction, and animal studies suggest that chondroitin may increase its efficacy. Two recent randomized, double-blind controlled trials have found no effect beyond placebo in reducing pain, while one found an effect beyond placebo.

Use

A typical dosage of glucosamine salt is 1,500 mg per day. Glucosamine contains an amino group that is positively charged at physiological pH. The anion included in the salt may vary. The amount of glucosamine present in 1500 mg of glucosamine salt will depend on which anion is present and whether additional salts are included in the manufacturer’s calculation. Glucosamine and chondroitin are “apparently poor candidates for transdermal [through the skin] absorption”, but glucosamine’s metabolite N-acetyl-D-glucosamine (NAG) appears to be a better candidate. The ability of NAG to permeate the skin is enhanced by ethanol and dimethyl sulfoxide (DMSO). DMSO is used to help deliver drugs in veterinary care, but is not approved for use on humans.

Glucosamine is a popular alternative medicine used by consumers for the treatment of osteoarthritis. Glucosamine is also extensively used in veterinary medicine as an unregulated but widely accepted supplement.

Contraindications

Clinical studies have consistently reported that glucosamine appears safe.

Allergy

Since glucosamine is usually derived from shellfish, those allergic to shellfish may wish to avoid it; however, since glucosamine is derived from the shells of these animals while the allergen is within the flesh of the animals, it is probably safe even for those with shellfish allergy. Alternative sources using fungal fermentation of corn are available.

Some commercially sold glucosamine supplements have other questionable ingredients added such as chinese skullcap, in addition to the more typical chondroitin, and MSM which is often seen too. “Allergic” type reaction may well be to these other ingredients and not the shellfish. People with reactions to these concoctions should also look at such things as red dyes and other needless additives. As noted above, the shellfish warning is just that warningresumably done by the lawyers and not because of a real problem.[citation needed] First hand experience with these since they first appeared in the USA has shown that the “red” pills are much more likely to cause a reaction, and the white ones do not unless chinese skullcap or other herbal additives are also included.[original research?]

Glucose metabolism

Another concern has been that the extra glucosamine could contribute to diabetes by interfering with the normal regulation of the hexosamine biosynthesis pathway, but several investigations have found no evidence that this occurs. A 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. It should be mentioned that the authors of the above mentioned review paper (Anderson et. al.) were financially supported by Cargill, Incorporated, Eddyville, IA, a manufacturer of glucosamine as mentioned in the acknowledgments section of the paper. 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.

Legal status

United States

In the United States, glucosamine is not approved by the Food and Drug Administration for medical use in humans. 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. 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 Europe, glucosamine is approved as a medical drug and is sold in the form of glucosamine sulphate. 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 sulphate a level of toxicity of 5 in a 0-100 scale, and recent OARSI (OsteoArthritis Research Society International) guidelines for hip and knee osteoarthritis also confirm its excellent safety profile.

Bioavailability and pharmacokinetics

Two recent studies confirm that glucosamine is bioavailable both systemically and at the site of action (the joint) after oral administration of crystalline glucosamine sulfate in osteoarthritis patients. Steady state glucosamine concentrations in plasma and synovial fluid were correlated and in line with those effective in selected in vitro studies.

The bioavailability of glucosamine sulfate is around 20%.

Natural sources

Glucosamine is naturally present in the shells of shellfish, animal bones and bone marrow. It is also present in some fungi, such as Aspergillus niger.

Pharmacodynamics

The possible effects of glucosamine sulfate in patients with osteoarthritis may be the result of its anti-inflammatory activity, the stimulation of the synthesis of proteoglycans, and the decrease in catabolic activity of chondrocytes inhibiting the synthesis of proteolytic enzymes and other substances that contribute to damage cartilage matrix and cause death of articular chondrocytes.

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.

Clinical studies

There have been multiple clinical trials of glucosamine as a medical therapy for osteoarthritis, but results have been conflicting. The evidence both for and against glucosamine’s efficacy has led to debate among physicians about whether to recommend glucosamine treatment to their patients.

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.

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This situation led the National Institutes of Health 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. The group of patients who took celecoxib did have a statistically significant improvement in their symptoms. These results suggest that glucosamine and chondroitin did not effectively relieve pain in the overall group of osteoarthritis patients, but it should be interpreted with caution because most patients presented only mild pain (thus a narrow margin to appraise pain improvement) and because of an unusual response to placebo in the trial (60%). However, exploratory analysis of a subgroup of patients suggested that the supplements taken together (glucosamine and chondroitin sulfate) may be significantly more effective than placebo (79.2% versus 54%; p = 0.002) and a 10% higher than the positive control, in patients with pain classified as moderate to severe (see testing hypotheses suggested by the data).

In an accompanying editorial, Dr. Marc Hochberg also noted that “It is disappointing that the GAIT investigators did not use glucosamine sulfate … since the results would then have provided important information that might have explained in part the heterogeneity in the studies reviewed by Towheed and colleagues” 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”. Thus the question of glucosamine’s efficacy will not be resolved without further updates or trials.

In this respect, a 6-month double-blind, multicenter trial has been recently performed to assess the efficacy of glucosamine sulfate 1500 mg once daily compared to placebo and acetaminophen in patients with osteoarthritis of the knee (GUIDE study). The results showed that glucosamine sulfate improved the Lequesne algofunctional index significantly compared to placebo and the positive control. Secondary analyses, including the OARSI responder indices, were also significantly favorable for glucosamine sulfate.

A subsequent meta-analysis of randomized controlled trials, including the NIH trial by Clegg, concluded that hydrochloride is not effective and that there was too much heterogeneity among trials of glucosamine sulfate to draw a conclusion. 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 2009 small study has concluded that glucosamine reduces cartilage turnover in osteoarthritis patients in response to physical training.

See also

Chitosan

Chitobiose

Methylsulfonylmethane

References

^ a b Horton D, Wander JD (1980). The Carbohydrates. Vol IB. New York: Academic Press. pp. 727728. ISBN 042-556351-5. 

^ “Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007”. National Center for Health Statistics. December 10, 2008. http://nccam.nih.gov/news/2008/nhsr12.pdf. Retrieved 2009-08-16. 

^ Ledderhose G (1877). Zeitschrift fr physiologische chemie ii: 213. 

^ Ledderhose G. Zeitschrift fr physiologische chemie iv: 139. 

^ Roseman S (2001). “Reflections on glycobiology” (free full text). J Biol Chem 276 (45): 4152742. doi:10.1074/jbc.R100053200. PMID 11553646. 

^ Ghosh S, Blumenthal HJ, Davidson E, Roseman S (1 May 1960). “Glucosamine metabolism. V. Enzymatic synthesis of glucosamine 6-phosphate”. J Biol Chem 235 (5): 1265. PMID 13827775. http://www.jbc.org/cgi/reprint/235/5/1265. 

^ International Union of Biochemistry and Molecular Biology

^ a b Buse MG (2006). “Hexosamines, insulin resistance, and the complications of diabetes: current status”. Am J Physiol Endocrinol Metab 290 (1): E18. doi:10.1152/ajpendo.00329.2005. PMID 16339923. 

^ Current Medical Diagnosis and Treatment 2008. McGraw-Hill Medical. 2008. ISBN 978-0071494304. 

^ Kirkham, SG; Samarasinghe, RK (2009). “Review article: Glucosamine”. Journal of orthopaedic surgery (Hong Kong) 17 (1): 726. PMID 19398798.  edit

^ Vangsness Jr, C.; Spiker, W.; Erickson, J. (2009). “A review of evidence-based medicine for glucosamine and chondroitin sulfate use in knee osteoarthritis”. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association 25 (1): 8694. doi:10.1016/j.arthro.2008.07.020. PMID 19111223.  edit

^ Towheed TE, Maxwell L, Anastassiades TP, et al. (2005). “Glucosamine therapy for treating osteoarthritis”. Cochrane Database Syst Rev (2): CD002946. doi:10.1002/14651858.CD002946.pub2. PMID 15846645.  Cochrane entry.

^ a b c Dahmer S, Schiller RM (August 2008). “Glucosamine”. Am Fam Physician 78 (4): 4716. PMID 18756654.  Free full-text.

^ Terry DE, Rees-Milton K, Smith P, Carran J, Pezeshki P, Woods C, Greer P, Anastassiades TP. (2005). “N-acylation of glucosamine modulates chondrocyte growth, proteoglycan synthesis, and gene expression”. J. Rheumatol. 32 (9): 177586. PMID 16142878. 

^ a b Clegg DO, Reda DJ, Harris CL, et al. (February 2006). “Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis”. N. Engl. J. Med. 354 (8): 795808. doi:10.1056/NEJMoa052771. PMID 16495392. 

^ Rozendaal RM, Koes BW, van Osch GJ, et al. (February 2008). “Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial”. Ann. Intern. Med. 148 (4): 26877. PMID 18283204. 

^ a b Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, et al. (February 2007). “Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator”. Arthritis Rheum. 56 (2): 55567. doi:10.1002/art.22371. PMID 17265490. 

^ a b PDR Health

^ Garner ST, Israel BJ, Achmed H, Capomacchia AC, Abney T, Azadi P (2007). “Transdermal permeability of N-acetyl-D-glucosamine”. Pharm Dev Technol 12 (2): 16974. doi:10.1080/10837450701212560. PMID 17510888. 

^ Gray HC, Hutcheson PS, Slavin RG (August 2004). “Is glucosamine safe in patients with seafood allergy?”. The Journal of Allergy and Clinical Immunology 114 (2): 45960. doi:10.1016/j.jaci.2004.05.050. PMID 15341031. 

^ Scroggie DA, Albright A, Harris MD (July 2003). “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”. Archives of Internal Medicine 163 (13): 158790. doi:10.1001/archinte.163.13.1587. PMID 12860582. 

^ Tannis AJ, Barban J, Conquer JA (June 2004). “Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals”. Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society 12 (6): 50611. doi:10.1016/j.joca.2004.03.001. PMID 15135147. 

^ Monauni T, Zenti MG, Cretti A, et al. (June 2000). “Effects of glucosamine infusion on insulin secretion and insulin action in humans”. Diabetes 49 (6): 92635. doi:10.2337/diabetes.49.6.926. PMID 10866044. 

^ Anderson JW, Nicolosi RJ, Borzelleca JF (February 2005). “Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy”. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association 43 (2): 187201. doi:10.1016/j.fct.2004.11.006. PMID 15621331. 

^ Muniyappa R, Karne RJ, Hall G, et al. (November 2006). “Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects”. Diabetes 55 (11): 314250. doi:10.2337/db06-0714. PMID 17065354. 

^ Pouwels MJ, Jacobs JR, Span PN, Lutterman JA, Smits P, Tack CJ (May 2001). “Short-term glucosamine infusion does not affect insulin sensitivity in humans”. The Journal of Clinical Endocrinology and Metabolism 86 (5): 2099103. doi:10.1210/jc.86.5.2099. PMID 11344213. 

^ Biggee BA, Blinn CM, Nuite M, Silbert JE, McAlindon TE (February 2007). “Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis”. Annals of the Rheumatic Diseases 66 (2): 2602. doi:10.1136/ard.2006.058222. PMID 16818461. 

^ “Dietary Supplements”. U.S. Food and Drug Administration. http://www.cfsan.fda.gov/~dms/supplmnt.html. Retrieved December 10, 2009. 

^ “Effects of Oral Glucosamine on Insulin and Blood Vessel Activity in Normal and Obese People”. ClinicalTrials.gov. June 23, 2006. http://www.clinicaltrials.gov/ct/show/NCT00065377. Retrieved December 10, 2009. 

^ Jordan KM, Arden NK, Doherty M, et al. (December 2003). “EULAR Recommendations 2003: an 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)”. Annals of the Rheumatic Diseases 62 (12): 114555. doi:10.1136/ard.2003.011742. PMID 14644851. 

^ Zhang W, Moskowitz RW, Nuki G, et al. (September 2007). “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”. Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society 15 (9): 9811000. doi:10.1016/j.joca.2007.06.014. PMID 17719803. 

^ 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): 10419. doi:10.1016/j.joca.2005.07.009. PMID 16168682. 

^ 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): 76472. doi:10.1016/j.joca.2007.01.019. PMID 17353133. 

^ Cohen MJ, Braun L (2007). Herbs & natural supplements: an evidence-based guide. Marrickville, New South Wales: Elsevier Australia. ISBN 0-7295-3796-X. 

^ 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 The EFSA Journal (2009) 1099, 1-19

^ Largo R, Alvarez-Soria MA, Dez-Ortego I, et al. (April 2003). “Glucosamine inhibits IL-1beta-induced NFkappaB activation in human osteoarthritic chondrocytes”. Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society 11 (4): 2908. PMID 12681956. .

^ Chan PS, Caron JP, Orth MW (July 2006). “Short-term gene expression changes in cartilage explants stimulated with interleukin beta plus glucosamine and chondroitin sulfate”. The Journal of Rheumatology 33 (7): 132940. PMID 16821268. 

^ Bassleer C, Rovati L, Franchimont P (November 1998). “Stimulation of proteoglycan production by glucosamine sulfate in chondrocytes isolated from human osteoarthritic articular cartilage in vitro”. Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society 6 (6): 42734. doi:10.1053/joca.1998.0146. PMID 10343776. 

^ Dodge GR, Jimenez SA (June 2003). “Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes”. Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society 11 (6): 42432. PMID 12801482. 

^ Chan PS, Caron JP, Orth MW (November 2005). “Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1-challenged bovine articular cartilage explants”. American Journal of Veterinary Research 66 (11): 18706. doi:10.2460/ajvr.2005.66.1870. PMID 16334942. 

^ Uitterlinden EJ, Jahr H, Koevoet JL, et al. (March 2006). “Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants”. Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society 14 (3): 2507. doi:10.1016/j.joca.2005.10.001. PMID 16300972. 

^ Chu SC, Yang SF, Lue KH, et al. (October 2006). “Glucosamine sulfate suppresses the expressions of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis”. Clinica Chimica Acta; International Journal of Clinical Chemistry 372 (1-2): 16772. doi:10.1016/j.cca.2006.04.014. PMID 16756968. 

^ a b Swarbrick J, ed (2006). Encyclopedia of Pharmaceutical Technology. 4 (Third ed.). Informa Healthcare. pp. 2436. ISBN 978-0-8493-9399-0. 

^ Manson JJ, Rahman A (January 2004). “This house believes that we should advise our patients with osteoarthritis of the knee to take glucosamine”. Rheumatology (Oxford, England) 43 (1): 1001. doi:10.1093/rheumatology/keg458. PMID 12867572. 

^ Adams ME (July 1999). “Hype about glucosamine”. Lancet 354 (9176): 3534. doi:10.1016/S0140-6736(99)90040-5. PMID 10437858. 

^ McAlindon TE, LaValley MP, Gulin JP, Felson DT (March 2000). “Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis”. JAMA : the Journal of the American Medical Association 283 (11): 146975. doi:10.1001/jama.283.11.1469. PMID 10732937. 

^ Reginster JY, Deroisy R, Rovati LC, et al. (January 2001). “Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial”. Lancet 357 (9252): 2516. doi:10.1016/S0140-6736(00)03610-2. PMID 11214126. 

^ Pavelk K, Gatterov J, Olejarov M, Machacek S, Giacovelli G, Rovati LC (October 2002). “Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study”. Archives of Internal Medicine 162 (18): 211323. doi:10.1001/archinte.162.18.2113. PMID 12374520. 

^ Hughes R, Carr A (March 2002). “A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee”. Rheumatology (Oxford, England) 41 (3): 27984. doi:10.1093/rheumatology/41.3.279. PMID 11934964. 

^ Cibere J, Kopec JA, Thorne A, et al. (October 2004). “Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis”. Arthritis and Rheumatism 51 (5): 73845. doi:10.1002/art.20697. PMID 15478160. 

^ Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY (July 2003). “Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis”. Archives of Internal Medicine 163 (13): 151422. doi:10.1001/archinte.163.13.1514. PMID 12860572. 

^ Bruyere O, Reginster JY (2007). “Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis”. Drugs & Aging 24 (7): 57380. doi:10.2165/00002512-200724070-00005. PMID 17658908. 

^ Clinicaltrials.gov

^ Towheed TE, Maxwell L, Anastassiades TP, et al. (2005). “Glucosamine therapy for treating osteoarthritis”. Cochrane Database of Systematic Reviews (Online) (2): CD002946. doi:10.1002/14651858.CD002946.pub2. PMID 15846645. 

^ Hochberg MC (February 2006). “Nutritional supplements for knee osteoarthritis–still no resolution”. The New England Journal of Medicine 354 (8): 85860. doi:10.1056/NEJMe058324. PMID 16495399. 

^ Vlad SC, LaValley MP, McAlindon TE, Felson DT (July 2007). “Glucosamine for pain in osteoarthritis: why do trial results differ?”. Arthritis and Rheumatism 56 (7): 226777. doi:10.1002/art.22728. PMID 17599746. 

^ a b Reginster JY (July 2007). “The efficacy of glucosamine sulfate in osteoarthritis: financial and nonfinancial conflict of interest”. Arthritis and Rheumatism 56 (7): 210510. doi:10.1002/art.22852. PMID 17599727. 

^ Petersen, G.; Saxne, T.; Heinegard, D.; Hansen, M.; Holm, L.; Koskinen, S.; Stordal, C.; Christensen, H. et al. (Jul 2009). “Glucosamine but not ibuprofen alters cartilage turnover in osteoarthritis patients in response to physical training1”. Osteoarthritis and Cartilage 18: 34. doi:10.1016/j.joca.2009.07.004. ISSN 1063-4584. PMID 19679221.  edit

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.

v  d  e

Dietary supplements

Types

Amino acids Bodybuilding supplement Energy drink Energy bar Fatty acids Herbal Supplements Minerals Prebiotics Probiotics (Lactobacillus, Bifidobacterium) Vitamins

Vitamins and minerals

Retinol (Vitamin A) B vitamins: Thiamine (B1) Riboflavin (B2) Niacin (B3) Pantothenic acid (B5) Pyridoxine (B6) Biotin (B7) Folic acid (B9) Cyanocobalamin (B12) Ascorbic acid (Vitamin C) Ergocalciferol and Cholecalciferol (Vitamin D) Tocopherol (Vitamin E) Naphthoquinone (Vitamin K) Calcium Choline Chlorine Chromium Cobalt Copper Fluorine Iodine Iron Magnesium Manganese Molybdenum Phosphorus Potassium Selenium Sodium Sulfur Zinc

Other common ingredients

AAKG Carnitine Chondroitin sulfate Cod liver oil Copper gluconate Creatine/Creatine supplements Dietary fiber Echinacea Elemental calcium Ephedra Fish oil Folic acid Ginseng Glucosamine Glutamine Grape seed extract Iron supplements Japanese Honeysuckle Krill oil Lingzhi Linseed oil Milk thistle Melatonin Red yeast rice Royal jelly Saw palmetto Spirulina St John’s wort Taurine Wheatgrass Wolfberry Yohimbine Zinc gluconate

Related articles

Codex Alimentarius Enzyte Metabolife Hadacol Nutraceutical Multivitamin Nutrition

v  d  e

Anti-inflammatory products (M01A)

Pyrazolidine/Butylpyrazolidines

Ampyrone  Clofezone  Kebuzone  Metamizole  Mofebutazone  Oxyphenbutazone  Phenazone  Phenylbutazone  Sulfinpyrazone

Acetic acid derivatives

and related substances

Aceclofenac  Acemetacin  Alclofenac  Bromfenac  Bumadizone  Bufexamac  Diclofenac  Difenpiramide  Etodolac  Fentiazac  Indometacin  Ketorolac  Lonazolac  Oxametacin  Proglumetacin  Sulindac  Tolmetin  Zomepirac

Oxicams

Ampiroxicam  Droxicam  Lornoxicam  Meloxicam  Piroxicam  Tenoxicam

Propionic acid derivatives

Alminoprofen  Benoxaprofen  Dexibuprofen  Dexketoprofen  Fenbufen  Fenoprofen  Flunoxaprofen  Flurbiprofen  Ibuprofen  Ibuproxam  Indoprofen  Ketoprofen  Naproxen  Oxaprozin  Pirprofen  Suprofen  Tiaprofenic acid

Fenamates

Flufenamic acid  Meclofenamic acid  Mefenamic acid  Tolfenamic acid

Coxibs

Celecoxib  Etoricoxib  Lumiracoxib  Parecoxib  Rofecoxib  Valdecoxib

Other

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Categories: Amino sugars | Monosaccharide derivatives | Monosaccharides | Dietary supplementsHidden categories: All articles with unsourced statements | Articles with unsourced statements from May 2009 | Articles with unsourced statements from December 2009 | All articles that may contain original research | Articles that may contain original research from December 2009

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