Glucosamine

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Clinical Studies
References


We combine 3 different forms of the glucosamine "family" in this product.  Each have subtle molecular differences to maximise their efficacy. The different forms are Glucosamine sulphate, Poly-N-acetyl-Glucosamine or Chitin, and D-Glucosamine hydrochloride.

General Info

Glucosamine is an amino sugar, which is a constituent of cartilage proteoglycans. It is derived from marine exoskeletons or produced synthetically. Glucosamine is required for the synthesis of glycoproteins, glycolipids and glycosaminoglycans (also known as mucopolysaccharides). These carbohydrate-containing compounds are found in tendons, ligaments, cartilage, synovial fluid, mucous membranes, structures in the eye, blood vessels and heart valves.

In osteoarthritis, Glucosamine stimulates metabolism of chondrocytes in the articular cartilage and of synovial cells in the synovial tissues. There is evidence that suggests that Glucosamine might have a disease-modifying effect, stopping or slowing the progression of osteoarthritis. Preliminary research suggests that Glucosamine inhibits protein N-Glycosylation and cytokine-stimulated production of mediators of inflammation and cartilage degradation. Glucosamine seems to inhibit interleukin 1-beta, IL-1beta, which stimulates the gene expression and protein synthesis of cyclooxygenase-2 (COX-2). Glucosamine doesn't seem to directly affect cyclooxygenase, which is responsible for anti-inflammatory and analgesic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) as well as adverse gastrointestinal effects. Glucosamine is used for osteoarthritis and temporomandibular joint (TMJ) arthritis.

Glucosamine encourages the cartilage to create the fundamental building material of the cartilage itself, proteoglycans and collagen. Glucosamine also has anti-inflammatory effects and prevents the creation of enzymes which can damage the cartilage. It’s main action is to stimulate the synthesis of cartilage in the joints. Also, by inhibiting the degradation of cartilage the effect can be relief from the pain and inflammation around joints that is associated with osteoarthritis.


D-Glucosamine-Hydrochloride

D-glucosamine hydrochloride is obtained from the shells of sea crustaceans. It is naturally contained in any healthy cartilage. D-Glucosamine HCL is a small molecule comprised of a sugar molecule (glucose), an amino group and a hydrochloride group.
 
This form is especially good for those with high blood pressure, on salt or potassium restricted diets or those having adverse reactions to sulfate. It has important physiological functions such as to take part in the detoxification of the liver and kidney, to protect liver from inflammation, to stimulate the increase of intestinal secretions, to treat rheummatoid arthritis and gastric ulcer, and to control the growth of cells.


Poly-N-acetyl-Glucosamine or Chitin

Chitosan is a polycationic polymer containing more than 5000 glucosamine units and is obtained by alkaline deacetylation of chitin (a N-acetyl-glucosamine polymer) from shellfish exo-skeletons. Chitosan is inexpensive, non-toxic and possesses potentially reactive amino functional groups. It is known to have a marked hypocholesterolemic effects, lowering cholesterol absorption in the lymphatic thoracic duct.


D-Glucosamine sulfate

D-glucosamine sulfate is an important nutritional factor used to maintain proper functioning of the joints and connective tissue. It relieves pain and inflammation of osteoarthritis, stimulates connective tissue reproduction, and helps arthritic joints. D-glucosamine sulfate has been shown to have beneficial results in dealing with the symptoms of osteoarthritis, the most common form of arthritis. The studies done with glucosamine sulfate actually suggest that it can help protect joint destruction, halting the disease, and has a healing effect on arthritic symptoms. Improvements do not come overnight, however, but the eventual effects can certainly rival those of prescription medications, without all the unwanted side-effects.

As well as this, it assistant cure functions to rheumatoid arthritis, heart disease pneumonia and fractures. Recently, it is found that D-glucosamine sulfate has good multifunction abilities to absorb free radicals, as well as potentially weight management.

 

 

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Published Clinical Studiescl top
Glucosamine

 1
Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy.

Anderson JW, Nicolosi RJ, Borzelleca JF.

 

Department of Internal Medicine, University of Kentucky, 1030 South Broadway, Suite 5, Lexington KY 40504-2681, USA. jwandersmd@aol.com

Glucosamine is widely used to relieve symptoms from osteoarthritis. Its safety and effects on glucose metabolism are critically evaluated in this review. The LD50 of oral glucosamine in animals is approximately 8000 mg/kg with no adverse effects at 2700 mg/kg for 12 months. Because altered glucose metabolism can be associated with parenteral administration of large doses of glucosamine in animals and with high concentrations in in vitro studies, we critically evaluated the clinical importance of these effects. Oral administration of large doses of glucosamine in animals has no documented effects on glucose metabolism. In vitro studies demonstrating effects of glucosamine on glucose metabolism have used concentrations that are 100-200 times higher than tissue levels expected with oral glucosamine administration in humans. We reviewed clinical trial data for 3063 human subjects. Fasting plasma glucose values decreased slightly for subjects after oral glucosamine for approximately 66 weeks. There were no adverse effects of oral glucosamine administration on blood, urine or fecal parameters. Side effects were significantly less common with glucosamine than placebo or non-steroidal anti-inflammatory drugs (NSAID). In contrast to NSAID, no serious or fatal side effects have been reported for glucosamine. Our critical evaluation indicates that glucosamine is safe under current conditions of use and does not affect glucose metabolism.

Publication Types:

PMID: 15621331 [PubMed - indexed for MEDLINE]

 

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Chondroprotective activity of N-acetylglucosamine in rabbits with experimental osteoarthritis.2

Shikhman AR, Amiel D, D'Lima D, Hwang SB, Hu C, Xu A, Hashimoto S, Kobayashi K, Sasho T, Lotz MK.

 

Division of Arthritis Research, The Scripps Research Institute, La Jolla, CA, USA. shikhman@scripps.edu

OBJECTIVE: To examine the therapeutic efficacy of N-acetylglucosamine (GlcNAc) in rabbits with experimental osteoarthritis (OA). METHODS: Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). In the first study, rabbits (six in each group) received intramuscular injections of GlcNAc or normal saline three times a week starting 1 week postoperatively. In the second study, rabbits (eight in each group) were injected intra-articularly with GlcNAc (either once or twice a week) or normal saline. In the third study, rabbits (seven in each group) were injected intra-articularly twice a week with either GlcNAc, hyaluronan, or normal saline. Animals were killed 8 weeks after ACLT for macroscopic and histological assessment of the knee joints. RESULTS: Intramuscular administration of GlcNAc in rabbits with experimental knee OA did not show chondroprotective effects but showed mild anti-inflammatory activity. In contrast, intra-articular administration of GlcNAc twice a week reduced cartilage degradation. Additionally, intra-articular GlcNAc also suppressed synovitis. Once a week intra-articular injections of GlcNAc did not demonstrate therapeutic efficacy. The chondroprotective efficacy of GlcNAc was better than that of viscosupplementation treatment with hyaluronan. CONCLUSION: Intra-articular GlcNAc has chondroprotective and anti-inflammatory activity in experimental OA.

PMID: 15608304 [PubMed - indexed for MEDLINE]

 

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[Slow-acting anti-rheumatic agents: recent developments]3

Van Linthoudt D, Gerster JC.

 

Services de Rhumatologie, Medecine physique et Rehabilitation. Daniel.VanLinthoudt@ne.ch

Until recently, treatment of osteoarthritis targeted the pain and the disability of the involved joints. It consisted in a mix of analgesics, anti-inflammatory drugs, steroid infiltrations and physical therapies. Usefulness of slow but long acting substances is increasing not only by their action on the symptoms but also because they positively influence the evolution of the disease. Some of them seem to induce a structural effect on the cartilage confirmed by a slow down of the joint space narrowing on successive radiographs of the knees. Presently, only basic matricial precursors such as chondroitin sulfate, glucosamine sulfate and hyaluronic acid are available in the clinic. They act by reducing cartilage destruction and enhancing chondrocyte anabolism. These preliminary results should be confirmed by further studies based on magnetic resonance imaging and surrogate markers of the cartilage matrix. Recent developments in the understanding of the physiopathology of osteoarthritis, including the key role of some cytokines, should allow new therapic ways, individually or in combination.

Publication Types:

PMID: 15552752 [PubMed - indexed for MEDLINE]

 

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Glucosamine and chondroitin sulfate are effective in the management of osteoarthritis.4

Hungerford DS, Jones LC.

 

Division of Arthritis Surgery, Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, G-1 Good Samaritan Professional Building, 5601 Loch Raven Boulevard, Baltimore, MD 21239, USA.

The use of glucosamine and chondroitin sulfate for the symptomatic treatment of osteoarthritis has been a subject of controversy for several reasons. First, the medical community in general took offense at the title of Theodosakis' book, The Arthritis Cure. Second, the medical community is becoming divided into "traditional" and "alternative" camps with deep skepticism between them. Third, the whole nutraceutical industry is essentially unregulated, with manufacturers making outrageous claims on products that have never been tested at all, are often of poor quality, and occasionally lacking in any active ingredient. However, for the nutriceuticals evaluated here, there is abundant in vitro, in vivo, animal clinical, and human clinical evidence of both their efficacy and safety. They deserve a prominent place in the armamentarium of nonsurgical treatment of osteoarthritis. Copyright 2003 Elsevier Inc. All rights reserved.

Publication Types:

PMID: 12730919 [PubMed - indexed for MEDLINE]

 

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Referencesre

  1. Adams ME. Hype about glucosamine. Lancet 1999;354:353.
  2. Balkan B, Dunning BE. Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats. Diabetes 1994;43:1173-9.
  3. Giaccari A, Morviducci L, Zorretta D, et al. In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia. Diabetologia 1995;38:518-24.
  4. Holmang A, Nilsson C, Niklasson M, et al. Induction of insulin resistance by glucosamine reduces blood flow but not interstitial levels of either glucose or insulin. Diabetes 1999;48:106-11.
  5. Kim YB, Zhu JS, Zierath JR, et al. Glucosamine infusion in rats rapidly impairs insulin stimulation of phosphoinositide 3-kinase but does not alter activation of Akt/protein kinase B in skeletal muscle. Diabetes 1999;48:310-20.
  6. Foerster KK, Schmid K, Rovati LC. Efficacy of glucosamine sulfate in osteoarthritis of the lumbar spine: a placebo-controlled, randomized, double-blind study. Am Coll Rheumatol 64th Ann Scientific Mtg, Philadelphia, PA: 2000;Oct 29- Nov 2:abstract 1613.
  7. Rindone JP, Hiller D, Collacott E, et al. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med 2000;172:91-4.
  8. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and Chondroitin for Treatment of Osteoarthritis A Systematic Quality Assessment and Meta-analysis. JAMA 2000;283:1469-75.
  9. Drovanti A, Bignamini AA, Rovati AA. Therapeutic activity of oral glucosamine sulfate in osteoarthrosis: a placebo-controlled, double-blind investigation. Clin Ther 1980;3:260-72.
  10. da Camara CC, Dowless GV. Glucosamine sulfate for osteoarthritis. Ann Pharmacother 1998;32:580-7.
  11. Lopes Vaz AL. Double-blind, clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients. Curr Med Res Opin 1982;8:145-9.
  12. Pujalte JM, Llavore EP, Ylescupidez FR. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Curr Med Res Opin 1980;7:110-4.
  13. Qiu GX, Gao SN, Giacovelli G, et al. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung 1998;48:469-74.
  14. Reichelt A. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebo-controlled, double-blind study. Arzneimittelforschung 1994;44:75-80.
  15. Forster K, Schmid K, Rovati L, et al. Longer-term treatment of mild-to-moderate osteoarthritis of the knee with glucosamine sulfate- a randomized controlled, double-blind clinical study. Euro J Clin Pharmacol 1996;50:542.
  16. Setnikar I, Palumbo R, Canali S, et al. Pharmacokinetics of glucosamine in man. Arzneimittelforschung 1993;43:1109-13.
  17. Barclay TS, Tsourounis C, McCart GM. Glucosamine. Ann Pharmacother 1998;32:574-9.
  18. Rossetti L, Hawkins M, Chen W, et al. In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats. J Clin Invest 1995;96:132-40.
  19. Shankar RR, Zhu JS, Baron AD. Glucosamine infusion in rats mimics the beta-cell dysfunction of non-insulin-dependent diabetes mellitus. Metabolism 1998;47:573-7.
  20. Thie NM, Prasad NG, Major PW. Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial. J Rheumatol 2001;28:1347-55.