A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals

Cantox Health Sciences International, Mississauga, ON, Canada.
Diabetes/Metabolism Research and Reviews (Impact Factor: 3.55). 01/2011; 27(1):14-27. DOI: 10.1002/dmrr.1150
Source: PubMed


Glucosamine (GlcN) is a widely utilized dietary supplement that is used to promote joint health. Reports that oral GlcN supplementation at usual doses adversely affects glucose metabolism in subjects with impaired glucose tolerance have raised concerns that GlcN should be contraindicated in individuals with diabetes and those at risk for developing it. This review addresses its potential, when used at typical doses, to affect glucose metabolism and insulin sensitivity in healthy individuals and those with diabetes or ‘pre-diabetes’. Publicly available scientific information and data on GlcN were systematically compiled using the electronic search tool, Dialog®, and reviewed with special emphasis on human studies. In long-term clinical trials, including those containing subjects with type 2 diabetes or ‘pre-diabetes’, GlcN produced a non-significant lowering of fasting blood glucose concentrations in all groups of subjects treated for periods of up to 3 years. Owing to limitations in study design, conclusions based on studies that report adverse affects of GlcN on insulin sensitivity and glucose tolerance in pre-diabetic subjects are suspect. However, no definitive long-term studies of GlcN use for individuals with pre-diabetes are available. Nevertheless, based on available evidence, we conclude that GlcN has no effect on fasting blood glucose levels, glucose metabolism, or insulin sensitivity at any oral dose level in healthy subjects, individuals with diabetes, or those with impaired glucose tolerance.
Copyright © 2010 John Wiley & Sons, Ltd.

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Available from: Anthony R. Leeds, Aug 28, 2014
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    • "Despite these findings in animal models, reports in humans stand divided and although some research suggests metabolic effects for these supplements [50, 104], most clinical trials and meta-analyses suggest this link is not as much clear in humans (Table 2). Moreover, a great part of these studies—including clinical assays [100, 101] and meta-analyses [102, 103]—were carried out on subjects with already impaired glucose metabolism, obscuring the interpretation of their results. Nevertheless, several studies have failed to find associations between GluN administration and insulin resistance as assessed by its gold standard test, the euglycemic insulin clamp (EIC). "
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    ABSTRACT: Osteoarthritis is a chronic degenerative disorder that currently represents one of the main causes of disability within the elderly population and an important presenting complaint overall. The pathophysiologic basis of osteoarthritis entails a complex group of interactions among biochemical and mechanical factors that have been better characterized in light of a recent spike in research on the subject. This has led to an ongoing search for ideal therapeutic management schemes for these patients, where glucosamine is one of the most frequently used alternatives worldwide due to their chondroprotective properties and their long-term effects. Its use in the treatment of osteoarthritis is well established; yet despite being considered effective by many research groups, controversy surrounds their true effectiveness. This situation stems from several methodological aspects which hinder appropriate data analysis and comparison in this context, particularly regarding objectives and target variables. Similar difficulties surround the assessment of the potential ability of glucosamine formulations to alter glucose metabolism. Nevertheless, evidence supporting diabetogenesis by glucosamine remains scarce in humans, and to date, this association should be considered only a theoretical possibility.
    Full-text · Article · Feb 2014
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    • "As referred to above glucosamine affects glucose metabolism due to its effects on GlcNAcylation. These effects are dose-dependent and the normal doses prescribed for osteoarthritis does not seem to impair glucose tolerance.26 Interestingly, when higher doses are used the substance impairs β-cell function in humans13 and in rodents.12 "
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    ABSTRACT: Impaired glucose tolerance and type 2 diabetes in rodents are associated with increased islet blood flow. If this is important for modulation of the endocrine function is at present unknown. We evaluated if glucosamine infusion, which induces peripheral insulin resistance and glucose intolerance, could be used to acutely increase islet blood flow. We infused anaesthetized Sprague-Dawley rats for 2 h with glucosamine (6 mg/kg body weight), in some cases followed by glucose administration. The former induced a 2-fold increase in serum insulin concentrations while plasma glucose remained unchanged. In vitro an augmented insulin response to hyperglycemia and decreased insulin content in batch type islet incubations with glucosamine for 24 h were seen. After 2 h glucosamine exposure in vitro, insulin release was decreased. In vivo glucosamine infusion increased islet blood flow, without affecting other regional blood flow values. Glucose increased islet blood flow to the same extent in control and glucosamine-infused rats. When exposed to 10 mmol/L glucosamine arterioles of isolated perfused islets showed a 10% dilation of their vascular smooth muscle. Thus, application of this model leads to acute hyperinsulinemia in vivo but a decreased insulin release in vitro, which suggests that effects not located to β-cells are responsible for the effects seen in vivo. An increased islet blood flow in previously healthy animals was also seen after glucose administration, which can be used to further dissect the importance of blood flow changes in islet function.
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    • "However, experimental studies using a euglycemic hyperinsulinemic clamp excluded a role of oral, intravenous, or intra-arterial glucosamine in the regulation of insulin sensitivity in humans [Muniyappa et al. 2006; Monauni et al. 2000; Pouwels et al. 2001]. Even recent reviews of clinical studies agree that the effects of glucosamine on glucose metabolism are questionable, if any [Dostrovsky et al. 2011; Simon et al. 2011]. However, since longitudinal data in diabetics are limited, caution might be advisable when treating patients with impaired glucose tolerance, and monitoring of blood glucose levels may be necessary in diabetics at the start or end of therapy. "
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    ABSTRACT: Glucosamine is an amino monosaccharide and a natural constituent of glycosaminoglycans in articular cartilage. When administered exogenously, it is used for the treatment of osteoarthritis as a prescription drug or a dietary supplement. The latter use is mainly supported by its perception as a cartilage building block, but it actually exerts specific pharmacologic effects, mainly decreasing interleukin 1-induced gene expression by inhibiting the cytokine intracellular signaling cascade in general and nuclear factor-kappa B (NF-kB) activation in particular. As a whole, the use of glucosamine in the management of osteoarthritis is supported by the clinical trials performed with the original prescription product, that is, crystalline glucosamine sulfate. This is the stabilized form of glucosamine sulfate, while other formulations or different glucosamine salts (e.g. hydrochloride) have never been shown to be effective. In particular, long-term pivotal trials of crystalline glucosamine sulfate 1500 mg once daily have shown significant and clinically relevant improvement of pain and function limitation (symptom-modifying effect) in knee osteoarthritis. Continuous administration for up to 3 years resulted in significant reduction in the progression of joint structure changes compared with placebo as assessed by measuring radiologic joint space narrowing (structure-modifying effect). The two effects combined may suggest a disease-modifying effect that was postulated based on an observed decrease in the risk of undergoing total joint replacement in the follow up of patients receiving the product for at least 12 months in the pivotal trials. The safety of the drug was good in clinical trials and in the postmarketing surveillance. Crystalline glucosamine sulfate 1500 mg once daily is therefore recommended in the majority of clinical practice guidelines and was found to be cost effective in pharmacoeconomic analyses. Compared with other glucosamine formulations, salts, or dosage forms, the prescription product achieves higher plasma and synovial fluid concentrations that are above the threshold for a pharmacologically relevant effect, and may therefore justify its distinct therapeutic characteristics.
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