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Glucosamine Side Effects

This page presents a limited Medline search on the subject of side effects of glucosamine, a naturally-occurring substance with claims to benefit patients suffering from arthritic conditions. It appears, based on the results of this search, that glucosamine has some deleterious effects on metabolism of glucose, both decreasing secretion of insulin and reducing its activity. If you are aware of other adverse effects of glucosamine, please email me at Paul Pinkhasik, M.D.

Title: Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats.
Title Abbreviation: Diabetes	Date of Pub: 1994 Oct
Author: Balkan B; Dunning BE;
Issue/Part/Supplement: 10	Volume Issue: 43	Pagination: 1173-9
MESH Headings: Animal; Arginine (AD/PD); Diabetes Mellitus, Non-Insulin-Dependent (PP); Glucokinase (AI); Glucosamine (PD); Glucose (AD/PD); Human; In Vitro; Infusions, Intravenous; Islets of Langerhans (DE/SE); Kinetics; Male; Rats; Rats, Sprague-Dawley;
Journal Title Code: E8X	Publication Type: JOURNAL ARTICLE
Date of Entry: 941103N	Entry Month: 9501
Country: UNITED STATES	Index Priority: 1
Language: Eng	Unique Identifier: 95011050
Unique Identifier: 95011050	ISSN: 0012-1797
Abstract: A characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) is the lack of an acute insulin response to intravenous glucose with maintenance of the response to other secretagogues. It has been hypothesized that impaired glucose sensing stems from defective beta-cell glucokinase. It remains unclear whether decreased pancreatic glucokinase activity will produce defects of insulin secretion similar to those observed in NIDDM. In this study, the effects of glucosamine on glucokinase activity and on islet function were assessed in vitro and in vivo. Glucosamine (5 mmol/l) reduced glucokinase activity in islet homogenate and diminished the insulin response to glucose (200 mg/dl) by isolated islets, whereas the response to arginine (20 mmol/l at 100 mg/dl glucose) was unaffected. In conscious normal rats, glucosamine lowered plasma insulin, followed by an increase in blood glucose. Administration of glucosamine 10 min before an infusion of glucose (10 mg.min-1. 15 min) reduced the insulin response. The primary effect was an attenuation of the first-phase insulin response relative to the decreased basal insulin levels. Arginine (10 mg.min-1.15 min) induced biphasic insulin release in both groups. Although glucosamine slightly reduced the absolute insulin response, it was normal relative to preinfusion levels. In all experiments, glucagon secretion was unaffected by glucosamine. The results indicate that glucosamine inhibits beta-cell glucokinase activity in vitro. In addition, glucosamine impairs glucose- but not arginine-induced insulin secretion. We conclude that glucosamine, probably via a reduction of glucokinase activity, impairs insulin secretion in a manner comparable to that seen in NIDDM.
Abstract By: Author
Address: Department of Diabetes, Sandoz Research Institute, Sandoz Pharmaceutical Corporation, East Hanover, New Jersey.

Title: Pharmacokinetics of glucosamine in man.
Title Abbreviation: Arzneimittelforschung		Date of Pub: 1993 Oct
Author: Setnikar I; Palumbo R; Canali S; Zanolo G;
Issue/Part/Supplement: 10	Volume Issue: 43	Pagination: 1109-13
MESH Headings: Administration, Oral; Adult; Feces (CH); Glucosamine (AD/AE/*PK); Half-Life; Human; Injections, Intramuscular; Injections, Intravenous; Male; Prodrugs;
Journal Title Code: 91U	Publication Type: JOURNAL ARTICLE
Date of Entry: 940125N	Entry Month: 9403
Country: GERMANY	Index Priority: 1
Language: Eng	Unique Identifier: 94092241
Unique Identifier: 94092241	ISSN: 0004-4172
Abstract: The pharmacokinetics of glucosamine sulfate (CAS 29031-19-4) was investigated in 6 healthy male volunteers (2 per administration route) using 14C uniformly labeled glucosamine sulfate and administering it in single dose by intravenous (i.v.), intramuscular (i.m.) or oral route. The results show that after i.v. administration the radioactivity due to glucosamine appears in plasma and is rapidly eliminated, with an initial t1/2 of 0.28 h. 1-2 h after administration the radioactivity due to glucosamine disappears almost completely and is replaced by a radioactivity originating from plasma proteins, in which glucosamine or its metabolites are incorporated. This radioactivity reaches a peak after 8-10 h and then declines with a t1/2 of 70 h. About 28% of the administered radioactivity is recovered in the urine of the 120 h following the administration and less than 1% is recovered in the feces. After i.m. administration similar pharmacokinetic patterns are observed. After oral administration a proportion close to 90% of glucosamine sulfate is absorbed. Free glucosamine is not detectable in plasma. The radioactivity incorporated in the plasma proteins follows pharmacokinetic patterns which are similar to those after i.v. or i.m. administration, but its concentration in plasma is about 5 times smaller than that after parenteral administration. The AUC after oral administration is 26% of that after i.v., or i.m. administration. The smaller plasma levels of radioactivity after oral administration are probably due to a first pass effect in the liver which metabolizes a notable proportion of glucosamine into smaller molecules and ultimately to CO2, water and urea.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract By: Author
Address: Rotta Research Laboratorium S.p.A., Monza, Italy.

Title: Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles. Study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptor [published erratum appears in Diabetes 1993 Oct; 42(10):1547]
Title Abbreviation: Diabetes	Date of Pub: 1993 Sep
Author: Robinson KA; Sens DA; Buse MG;
Issue/Part/Supplement: 9	Volume Issue: 42	Pagination: 1333-46
MESH Headings: Animal; Biological Transport (PH); Fibroblasts (ME); Glucosamine (PH); Glucose (ME); Glycogen (BI); Glycogen Synthase (ME); In Vitro; Insulin Resistance (PH); Male; Monosaccharide Transport Proteins (AN); Muscles (ME); Rats; Rats, Wistar; Receptors, Insulin (AN/ME); Support, U.S. Gov't, P.H.S.;
Journal Title Code: E8X	Publication Type: JOURNAL ARTICLE
Date of Entry: 930916N	Entry Month: 9311
Country: UNITED STATES	Index Priority: 1
Language: Eng	Unique Identifier: 93351767
Unique Identifier: 93351767	ISSN: 0012-1797
Abstract: Increased routing of glucose through the hexosamine-biosynthetic pathway has been implicated in the development of glucose-induced insulin resistance of glucose transport in cultured adipocytes. Because both glucosamine and glucose enter this pathway as glucosamine-6-phosphate, we examined the effects of preincubation with glucosamine in isolated rat diaphragms and in fibroblasts over expressing the human insulin receptor (HIR-cells). In muscles, pre-exposure to glucosamine inhibited subsequent basal and, to a greater extent, insulin-stimulated glucose transport in a time- and dose-dependent manner and abolished the stimulation by insulin of glycogen synthesis. Insulin receptor number, activation of the insulin receptor tyrosine kinase in situ and after solubilization, and the total pool of glucose transporters (GLUT4) were unaffected, and glycogen synthase was activated by glucosamine pretreatment. In HIR-cells, which express GLUT1 and not GLUT4, basal and insulin-stimulated glucose transport were unaffected by glucosamine, but glycogen synthesis was markedly inhibited. Insulin-stimulated activation of protein kinases (MAP and S6) was unaffected, and the fractional velocity and apparent total activity of glycogen synthase was increased in glucosamine-treated HIR-cells. In pulse-labeling studies, addition of glucosamine during the chase prolonged processing of insulin proreceptors to receptors and altered the electrophoretic mobility of proreceptors and processed alpha-subunits, consistent with altered glycosylation. Glucosamine-induced insulin resistance of glucose transport appears to be restricted to GLUT4-expressing cells, i.e., skeletal muscle and adipocytes; it may reflect impaired translocation of GLUT4 to the plasmalemma. The glucosamine-induced imbalance in UDP sugars, i.e., increased UDP-N-acetylhexosamines and decreased UDP-glucose, may alter glycosylation of critical proteins and limit the flux of glucose into glycogen.
Abstract By: Author
Address: Department of Medicine, Medical University of South Carolina, Charleston.
Last Revision Date: 931221

Title: Effects of glucosamine on insulin-stimulated glucose metabolism in rat soleus muscle.
Title Abbreviation: Int J Biochem Cell Biol		Date of Pub: 1995 Aug
Author: Fьrnsinn C; Sanderson AL; Radda GK; Leighton B;
Issue/Part/Supplement: 8	Volume Issue: 27	Pagination: 805-14
MESH Headings: Animal; Biological Transport; Deoxyglucose (ME); Glucosamine (PD); Glucose (ME); Glycogen (ME); Glycolysis (PH); Insulin (PD); Lactates (ME); Male; Muscle, Skeletal (DE/ME); Phosphorylation; Radioligand Assay; Rats; Rats, Wistar; Stimulation, Chemical;
Journal Title Code: CDK	Publication Type: JOURNAL ARTICLE
Date of Entry: 951207N	Entry Month: 9602
Country: ENGLAND	Index Priority: 2
Language: Eng	Unique Identifier: 96078937
Unique Identifier: 96078937	ISSN: 1357-2725
Abstract: Intracellular accumulation of glucosamine metabolites (which can be achieved by pre-incubation of cells with glucosamine) during hyperglycemia may decrease the rate of insulin-mediated glucose transport in cells. Soleus muscle preparations were pre-incubated in the presence or absence of glucosamine in media that contained glutamine (Dulbecco's modified Eagle medium, DMEM; Medium 199, M199) or devoid of glutamine (Krebs-Henseleit's buffer, KHB). Subsequently, muscles were transferred to fresh media, in the absence of glucosamine, but with various concentrations of insulin and the rates of 2-deoxyglucose transport or intracellular glucose metabolism were measured. Glucosamine pre-exposure decreased both insulin-stimulated (1000 microU/ml) glucose transport and phosphorylation. The percentage decreases for 3H-2-deoxyglucose transport after pre-incubation with 40 mM glucosamine compared with untreated muscles were: DMEM, 48%; KHB, 50%; M199, 29%. The percentage decreases for 3H-2-deoxyglucose-6-phosphate accumulation were: DMEM, 53%; KHB 60%; M199, 37%. In DMEM and KHB, glucosamine pre-treatment of soleus muscle preparations markedly decreased the rate of lactate release and stimulated the rate of 14C-glucose incorporation into glycogen. Thus, a distinct shift of glucosyl units from glycolysis to glycogenesis occurred with low and high insulin concentrations. For the latter (1000 microU of insulin/ml) the ratio of moles of glucose converted to lactate divided by moles of glucose incorporated into glycogen in muscles pre-incubated in the absence or presence of glucosamine (40 mM) was, respectively: DMEM, 4.34 + 0.52 vs 1.55 + 0.06, P < 0.001; KHB, 2.80 + 0.44 vs 0.76 + 0.03, P < 0.005). Glycogen synthesis was not stimulated in muscles pre-exposed to glucosamine in M199. In muscles pre-incubated to glucosamine and incubated in DMEM or KHB, there was a marked shift of glucose transported into the cell from glycolysis to glycogenesis. Thus, glucosamine or its metabolites had distinct effects on intracellular glucose handling.
Abstract By: Author
Address: Department of Biochemistry, University of Oxford, U.K.
Last Revision Date:

Title: In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycemia.
Title Abbreviation: Diabetologia	Date of Pub: 1995 May
Author: Giaccari A; Morviducci L; Zorretta D; Sbraccia P; Leonetti F; Caiola S; Buongiorno A; Bonadonna RC; Tamburrano G;
Issue/Part/Supplement: 5	Volume Issue: 38	Pagination: 518-24
MESH Headings: Animal; Arginine (PD); Blood Glucose (DE/ME); Comparative Study; Gluconeogenesis (DE); Glucosamine (PD); Glucose Clamp Technique; Homeostasis; Hyperglycemia (BL/PP); Insulin (BL/PD/SE); Insulin Resistance (*PH); Liver (DE/ME); Male; Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't;
Journal Title Code: E93	Publication Type: JOURNAL ARTICLE
Date of Entry: 960104N	Entry Month: 9603
Country: GERMANY	Index Priority: 2
Language: Eng	Unique Identifier: 96110360
Unique Identifier: 96110360	ISSN: 0012-186X
Abstract: We tested the hypothesis that glucosamine, a putative activator of glucose toxicity in vitro through acceleration of the hexosamine pathway, may determine in vivo the two key features of glucose toxicity in diabetes, namely, peripheral insulin resistance and decreased insulin secretion. Two groups of awake rats were studied either with intra-arterial administration of glucosamine (5 mumol.kg-1.min-1) or saline. Insulin secretion was determined after arginine, glucose (hyperglycaemic clamp), and arginine/glucose infusions, while insulin-mediated glucose metabolism was assessed by the euglycaemic hyperinsulinaemic clamp in combination with [3-3H]-glucose infusion. Glucosamine had no effects on arginine-induced insulin secretion both at euglycaemia and hyperglycaemia, but significantly (40-50%) impaired glucose-induced insulin secretion (both first and second phases). During euglycaemic hyperinsulinaemic clamp studies, glucosamine decreased glucose uptake by approximately 30%, affecting glycolysis (estimated from 3H2O rate of appearance) and muscle glycogen synthesis (calculated from accumulation of [3H]-glucosyl units in muscle glycogen) to a similar extent. Muscle glucose 6-phosphate concentration was markedly reduced in the glucosamine-infused rats, suggesting an impairment in glucose transport/phosphorylation. Therefore, an increase in hexosamine metabolism in vivo: 1) inhibits glucose-induced insulin secretion, and 2) reduces insulin stimulation of both glycolysis and glycogen synthesis, thereby mimicking in normal rats the major alterations due to glucose toxicity in diabetes.
Abstract By: Author
Address: Laboratory of Clinical Biochemistry, Istituto Superiore di Sanitа, Rome, Italy.
Last Revision Date: 2

Title: Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomized, placebo-controlled, double-blind study.
Title Abbreviation: Arzneimittelforschung	Date of Pub: 1994 Jan
Author: Reichelt A; Fцrster KK; Fischer M; Rovati LC; Setnikar I;
Issue/Part/Supplement: 1	Volume Issue: 44	Pagination: 75-80
MESH Headings: Adult; Aged; Double-Blind Method; Female; Glucosamine (AD/AE/TU); Human; Injections, Intramuscular; Knee Joint (); Male; Middle Age; Osteoarthritis (CO/*DT/PA); Pain (DT/ET);
Journal Title Code: 91U	Publication Type: CLINICAL TRIAL
Date of Entry: 960104N	Entry Month: 9603
Country: GERMANY	Index Priority: 2
Unique Identifier: 94183329	ISSN: 0004-4172
Abstract: Glucosamine sulfate (Dona, CAS 29031-19-4) is a drug used in the treatment of osteoarthritis. When orally given, it is more effective than placebo and at least as effective as non-steroidal anti-inflammatory drugs in relieving osteoarthritis symptoms. The aim of this multicentre, randomized, placebo-controlled, double-blind, parallel-group study was to assess the efficacy and safety of glucosamine sulfate intramuscularly given on the same parameters. 155 out-patients with knee osteoarthritis (Lequesne's criteria), radiological stage between I and III, Lequesne's severity index of at least 4 points and symptoms for at least 6 months, were treated with i.m. glucosamine sulfate (or placebo) 400 mg twice a week for 6 weeks. Clinic visits were performed at enrollment, after a 2-week baseline, at weekly intervals during treatment and 2 weeks after drug discontinuation. Responders to treatment were considered those patients with a reduction of at least 3 points in the Lequesne index, together with a positive overall judgment by the investigator. The Lequesne index was slightly over 10 points in average in both groups at the beginning of treatment. A significant decrease in the index was observed for glucosamine compared to placebo (3.3 vs. 2.0 points in average, respectively; p < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (n = 73) and only 33% (n = 69) with placebo (p = 0.012, Fisher's Exact Test). According to the intention-to-treat approach, considering also drop-outs, these proportions were 51% vs. 30% (p = 0.015). (ABSTRACT TRUNCATED AT 250 WORDS)
Abstract By: Author
Address: University Clinic of Orthopedics, Freiburg/Brsg. Fed. Rep. of Germany.
Last Revision Date: 2

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