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.

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.

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Published Clinical Studiescl top
Glucosamine

• Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy.
• Chondroprotective activity of N-acetylglucosamine in rabbits with experimental osteoarthritis.
• [Slow-acting anti-rheumatic agents: recent developments]
• Glucosamine and chondroitin sulfate are effective in the management of osteoarthritis.

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:

• Review

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:

• Review
• Review, Tutorial

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:

• Review
• Review, Tutorial

PMID: 12730919 [PubMed - indexed for MEDLINE]

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Referencesre

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