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GLUCOSAMINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Glucosamine is an amino-monosaccharide used for the treatment of rheumatic disorders and used as a pharmaceutical aid.

Specific Substances

    1) 2-Amino-2-deoxy-beta-D-glucopyranose
    2) 2-Amino-2-deoxy-beta-D-glucose
    3) 2-Amino-2-deoxyglucose
    4) Chitosamine
    5) NSC-758
    6) Molecular formula: C6-H13-NO5
    7) CAS 3416-24-8 (glucosamine)
    8) CAS 66-84-2 (glucosamine hydrochloride)
    9) CAS 2002-25-7 (glucosamine hydrochloride)
    10) CAS 29031-19-4 (glucosamine sulfate)

Available Forms Sources

    A) FORMS
    1) Glucosamine is available in capsules, tablets, or powdered form. Often, it is available in combination with chondroitin. Capsules containing 314 mg crystalline glucosamine sulfate, corresponding to 250 mg glucosamine have been used in European clinical studies (Qiu et al, 1998). Glucosamine sulfate is available through herbal centers as 500 mg capsules.
    B) SOURCES
    1) Endogenously, glucosamine is an amino-monosaccharide used physiologically in the human body as a substrate for the biosynthesis of glycosaminoglycans and proteoglycans of the cartilage matrix. It is synthesized in the chondrocytes by amination of glucose (Qiu et al, 1998).
    2) Exogenously, glucosamine is isolated from chitin or prepared synthetically. It is found in chitin, mucoproteins, and mucopolysaccharides (S Sweetman , 2002; Budavari, 1996).
    C) USES
    1) Glucosamine is used extensively in Europe and Asia, and currently in the United States, as a selective symptom modifying drug for osteoarthritis. It is reported to normalize and stimulate the biosynthesis of proteoglycans of cartilage matrix, thus stopping or slowing the degenerative process of articular cartilages, the pathogenic mechanism of osteoarthritis (Qiu et al, 1998).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Glucosamine is a supplement used as an adjunctive therapy for osteoarthritis.
    B) PHARMACOLOGY: Glucosamine is theorized to normalize and stimulate the biosynthesis of proteoglycans of cartilage matrix, thus stopping or slowing the degenerative process of articular cartilages, the pathogenic mechanism of osteoarthritis.
    C) EPIDEMIOLOGY: Glucosamine is widely used, but reports of toxicity from overdose are rare.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Adverse events are minimal. COMMON: Nausea, vomiting, abdominal pain, and diarrhea. LESS COMMON: Peripheral edema, tachycardia, rash, pruritus, painful, heavy legs, and edema, drowsiness, headache and insomnia.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: Overdose effects from glucosamine have not yet been reported.
    0.2.20) REPRODUCTIVE
    A) No teratogenic effects were noted in animals following glucosamine therapy. At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Laboratory Monitoring

    A) Monitor vital signs.
    B) Routine laboratory testing is not necessary unless otherwise clinically indicated. Serum glucosamine concentrations are not widely available or clinically useful in managing overdose.
    C) Monitor fluid and electrolyte status in patients with severe diarrhea and/or vomiting.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) There is no specific treatment for severe glucosamine overdose other than supportive care.
    C) DECONTAMINATION
    1) PREHOSPITAL: Gastrointestinal decontamination is generally NOT necessary.
    2) HOSPITAL: Gastrointestinal decontamination is generally NOT necessary. Activated charcoal is recommended in symptomatic patients and those with significant coingestants.
    D) AIRWAY MANAGEMENT
    1) Airway management is very unlikely to be necessary unless other toxic agents have been administered concurrently.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION PROCEDURE
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent, however as severe toxicity has not been reported, enhanced elimination is unlikely to be necessary. Glucosamine has an approximate volume of distribution of 2.5 L and is bound to plasma proteins.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: An asymptomatic adult or child with an inadvertent minor exposure (eg, a single dietary supplement ingested by a young child) may be monitored at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate self-harm ingestion or significant symptoms should be evaluated in a healthcare facility and monitored. Patients may be discharged to home, if no symptoms develop or symptoms have resolved and laboratory studies are within normal limits.
    3) ADMISSION CRITERIA: Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) When managing a suspected glucosamine overdose, the possibility of multidrug involvement should be considered.
    I) PHARMACOKINETICS
    1) Bioavailability is approximately 26% following oral administration. Glucosamine is not protein-bound, but rather incorporates into plasma proteins (primarily globulins) and volume of distribution (Vd) is 2.5 L. Metabolism occurs mainly in the liver. Renal excretion is 10% following oral administration and fecal excretion following an oral dose is approximately 11%, with most being unabsorbed drug.
    J) DIFFERENTIAL DIAGNOSIS
    1) Severe toxicity is not expected for glucosamine overdose. In patients presenting with severe symptoms, treatment should be guided based on the possibility of coingestant toxicity.

Range Of Toxicity

    A) A specific toxic dose has not been established. There are no published reports of acute ingestions resulting in toxicity. Adverse effects appear to be minimal, consisting mostly of gastric effects.
    B) THERAPEUTIC DOSE: ORAL: Glucosamine sulfate 500 mg orally 3 times daily has been used for periods of 2 weeks to 3 months. INTRAVENOUS: 400 mg intravenously once daily for one week were given. INTRAMUSCULAR: Glucosamine sulfate doses of 400 mg intramuscularly have been given once daily for one week or 400 mg twice weekly for 6 weeks.

Clinical Effects

Summary Of Exposure

    A) USES: Glucosamine is a supplement used as an adjunctive therapy for osteoarthritis.
    B) PHARMACOLOGY: Glucosamine is theorized to normalize and stimulate the biosynthesis of proteoglycans of cartilage matrix, thus stopping or slowing the degenerative process of articular cartilages, the pathogenic mechanism of osteoarthritis.
    C) EPIDEMIOLOGY: Glucosamine is widely used, but reports of toxicity from overdose are rare.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Adverse events are minimal. COMMON: Nausea, vomiting, abdominal pain, and diarrhea. LESS COMMON: Peripheral edema, tachycardia, rash, pruritus, painful, heavy legs, and edema, drowsiness, headache and insomnia.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: Overdose effects from glucosamine have not yet been reported.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH THERAPEUTIC USE
    a) Adverse effects of peripheral edema and tachycardia have been reported in a few patients in larger clinical trials investigating oral or intramuscular glucosamine in osteoarthritis patients (Reichelt et al, 1994; Tapadinhas et al, 1982). No causal relationship has been established.

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) Infrequent adverse effects observed during oral glucosamine therapy have included drowsiness, headache, and insomnia (less than 1% of patients) (Barclay et al, 1998; Qiu et al, 1998; Tapadinhas et al, 1982).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTRITIS
    1) WITH THERAPEUTIC USE
    a) Mild adverse effects during clinical trials of oral glucosamine in therapy of osteoarthritis have included nausea, dyspepsia, vomiting, abdominal or epigastric pain, constipation, diarrhea, heartburn, and anorexia (Barclay et al, 1998; da Camara & Dowless, 1998; Qiu et al, 1998) (Mueller & Fassbender et al, 1994)(Tapadinhas et al, 1982; Drovanti et al, 1980). Gastrointestinal adverse effects seem to be the most common finding in clinical trials.
    b) INCIDENCE: In a large open trial (n=1208), the most common adverse effects with oral glucosamine (1.5 g daily) were epigastric pain (3.5%), heartburn (2.7%), diarrhea (2.5%), and nausea (1%) (Tapadinhas et al, 1982).
    c) Gastrointestinal effects observed with intramuscular glucosamine sulfate have been nausea and vomiting, and these events were rare (Reichelt et al, 1994).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) INFLAMMATORY DISEASE OF LIVER
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 65-year-old healthy man was admitted with a 1 week history of abdominal pain, fatigue and jaundice without fever. He had a previous history of ingesting a dietary supplement containing glucosamine and chondroitin sulfate that he had stopped 1 week prior to hospitalization. Initial laboratory studies showed elevated liver enzymes (eg, ASAT 1614 International Units/L; ALAT 2744 International Units/L and AP 199 International Units/L) an elevated serum lactate dehydrogenase (563 International Units/L) and bilirubin (7.7 mg/dL) and coagulopathy and hypoproteinemia; electrolytes and renal function were normal. An abdominal ultrasound and serological viral testing were both negative. A liver biopsy showed severe necrotic inflammation and marked interface hepatitis consistent with autoimmune hepatitis. Initial therapy included IV methylprednisone followed by prednisolone for an extended period (about 3 months) (von Felden et al, 2013).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Erythema and pruritus have been reported as infrequent adverse effects following oral or intramuscular glucosamine sulfate therapy in clinical trials (Barclay et al, 1998; Reichelt et al, 1994; Tapadinhas et al, 1982).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) WITH THERAPEUTIC USE
    a) Painful, heavy legs and edema were reported as adverse effects in 2 patients (n=79) in a clinical trial (Reichelt et al, 1994). No causal relationship was established.

Reproductive

    3.20.1) SUMMARY
    A) No teratogenic effects were noted in animals following glucosamine therapy. At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) No teratogenic effects were noted in mice or rabbits following glucosamine therapy (S Fabro , 1999).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Genotoxicity

    A) During animal studies, glucosamine was suspected of inhibiting DNA replication in human and mouse lymphocytes (RTECS , 2001; S Fabro , 1999). Other mutation tests were positive in mouse lymphocytes (RTECS , 2001).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs.
    B) Routine laboratory testing is not necessary unless otherwise clinically indicated. Serum glucosamine concentrations are not widely available or clinically useful in managing overdose.
    C) Monitor fluid and electrolyte status in patients with severe diarrhea and/or vomiting.
    4.1.2) SERUM/BLOOD
    A) TOXICITY
    1) Serum glucosamine levels are not clinically useful or readily available. Toxic serum levels of glucosamine have not been established.
    B) BLOOD/SERUM CHEMISTRY
    1) Monitor fluid and electrolyte levels as indicated in patients with severe vomiting or diarrhea.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor vital signs in symptomatic patients.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    6.3.1.2) HOME CRITERIA/ORAL
    A) An asymptomatic adult or child with an inadvertent minor exposure (eg, a single dietary supplement ingested by a young child) may be monitored at home.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate self-harm ingestion or significant symptoms should be evaluated in a healthcare facility and monitored. Patients may be discharged to home, if no symptoms develop or symptoms have resolved and laboratory studies are within normal limits.

Monitoring

    A) Monitor vital signs.
    B) Routine laboratory testing is not necessary unless otherwise clinically indicated. Serum glucosamine concentrations are not widely available or clinically useful in managing overdose.
    C) Monitor fluid and electrolyte status in patients with severe diarrhea and/or vomiting.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) At the time of this review, numerous studies have reported NO or mild adverse events following glucosamine exposure. Gastrointestinal decontamination is generally NOT necessary unless more toxic coingestants are involved.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) At the time of this review, numerous studies have reported NO or mild adverse events following glucosamine exposure. Gastrointestinal decontamination is generally NOT necessary. Activated charcoal is recommended in symptomatic patients and those with significant coingestants.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no specific treatment for glucosamine overdose other than supportive care.
    B) MONITORING OF PATIENT
    1) Monitor vital signs in all symptomatic exposures. Routine laboratory testing is not necessary unless otherwise clinically indicated. Serum glucosamine concentrations are not widely available or clinically useful in managing overdose. Monitor fluid status as indicated in patients with symptoms of severe diarrhea or vomiting.

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent, however since severe toxicity has not been reported enhanced elimination is unlikely to be necessary. Glucosamine has an approximate volume of distribution of 2.5 L and is bound to plasma proteins.

Range Of Toxicity

Summary

    A) A specific toxic dose has not been established. There are no published reports of acute ingestions resulting in toxicity. Adverse effects appear to be minimal, consisting mostly of gastric effects.
    B) THERAPEUTIC DOSE: ORAL: Glucosamine sulfate 500 mg orally 3 times daily has been used for periods of 2 weeks to 3 months. INTRAVENOUS: 400 mg intravenously once daily for one week were given. INTRAMUSCULAR: Glucosamine sulfate doses of 400 mg intramuscularly have been given once daily for one week or 400 mg twice weekly for 6 weeks.

Therapeutic Dose

    7.2.1) ADULT
    A) DISEASE STATE
    1) OSTEOARTHRITIS -
    a) INTRAMUSCULAR - Glucosamine sulfate doses of 400 milligrams intramuscularly have been given once daily for one week (D'Ambrosio et al, 1981; Crolle & D'Este, 1980) or 400 milligrams twice weekly for 6 weeks (Reichelt et al, 1994) in clinical studies.
    b) INTRAVENOUS - In a clinical study, glucosamine sulfate doses of 400 milligrams intravenously once daily for one week were given (D'Ambrosio et al, 1981).
    c) ORAL - Glucosamine sulfate 500 milligrams orally 3 times daily has been used for periods of 2 weeks to 3 months (Tapadinhas et al, 1982; Pujalte et al, 1980; D'Ambrosio et al, 1981; Crolle & D'Este, 1980; Drovanti et al, 1980; Qiu et al, 1998; da Camara & Dowless, 1998; Mueller-Fassbender et al, 1994).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) GLUCOSAMINE HYDROCHLORIDE
    1) LD50- (ORAL)MOUSE:
    a) 15 g/kg (RTECS, 2001)
    2) LD50- (SUBCUTANEOUS)MOUSE:
    a) 6200 mg/kg (RTECS, 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Glucosamine is an endogenous amino-monosaccharide synthesized from glucose and utilized for biosynthesis of glycoproteins and glycosaminoglycans (Reichelt et al, 1994; Setnikar et al, 1993; Reuser & Wisselaar, 1994). Glucosamine has been investigated clinically in osteoarthritis, as the sulfate salt, due to early studies suggesting altered glucosamine metabolism contributing to development of osteoarthritis.
    B) Preclinical studies with glucosamine have suggested tropism of this compound for cartilage and bone, and that it serves as a preferred substrate for, and stimulant of, proteoglycan biosynthesis; proteoglycans are essential components of articular cartilage (D'Ambrosio et al, 1981; Vidal y Plana et al, 1978; Setnikar et al, 1993; Mueller-Fassbender et al, 1994). Exogenous administration in animals has been reported to retard cartilage degradation and rebuild experimentally damaged cartilage tissue (Crolle & D'Este, 1980; D'Ambrosio et al, 1981) Pujalte et al, 1981).
    1) Glucosamine enhances cartilage proteoglycan synthesis, thereby inhibiting deterioration of cartilage brought about by osteoarthritis and helping to maintain an equilibrium between cartilage catabolic and anabolic processes (Vidal y Plana & Karzel, 1980). An antiinflammatory action of glucosamine has also been proposed, unrelated to cyclooxygenase inhibition (Reichelt et al, 1994).
    C) Collectively, the above data suggest disease-modifying activity of glucosamine. Claims that glucosamine can halt the degenerative process in osteoarthritis have been made (Pujalte et al, 1980; McCarty, 1994; Reichelt et al, 1994). However, these preclinical data require corroboration under well-controlled conditions; clinical evidence of this effect is lacking.
    1) Currently, glucosamine is classified by the International League Against Rheumatism as a "Symptomatic Slow-Acting Drug in Osteoarthritis (SYSADOA)". This group of drugs is characterized by slow-onset improvement in osteoarthritis and persistent benefits after discontinuation. Other drugs placed in the SYSADOA class include chondroitin sulfate and hyaluronic acid (Higgins, 1993). Glucosamine has never been considered a Disease Modifying Osteoarthritis Drug (DMOAD) by any organization.
    D) Results of an in vivo/in vitro study have suggested the ability of glucosamine to impair insulin secretion, presumably via beta-cell glucokinase inhibition. This effect was similar to the defective beta-cell function observed in patients with non-insulin-dependent diabetes mellitus (Balkan & Dunning, 1994).
    E) In one animal study, it was found that glucosamine impairs glucose-induced insulin release, probably through the inhibition of glucose metabolism. It was suggested that the accumulation of glucosamine in islets under high glucose atmosphere may partly account for the mechanism for glucose toxicity (Yoshikawa et al, 2002).
    F) One in vitro study demonstrated that glucosamine suppresses the activation of T-lymphoblasts and dendritic cells, as well as allogeneic mixed leukocyte reactivity in a dose-dependent manner. In addition, glucosamine use increased the allogeneic cardiac allograft survival in vivo. The authors concluded that glucosamine possesses immunosuppressive activity (Ma et al, 2002).

Physicochemical

Physical Characteristics

    A) Synthetic glucosamine is a crystalline powder (Budavari, 1996).

Molecular Weight

    1) Glucosamine: 179.2
    2) Glucosamine HCl: 215.7

References

General Bibliography

    1) Balkan G & Dunning BE: Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats. Diabetes 1994; 43:1173-1179.
    2) Barclay TS, Tsourounis C, & McCart GM: Glucosamine. Ann Pharmacother 1998; 32:574-580.
    3) Budavari S: The Merck Index, 12th ed, Merck & Co, Inc, Whitehouse Station, NJ, 1996, pp 758.
    4) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    5) Crolle G & D'Este E: Glucosamine sulphate for the management of arthrosis: a controlled clinical investigation. Curr Med Res Opin 1980; 7:104-109.
    6) D'Ambrosio E, Casa B, & Bompani R: Glucosamine sulphate: a controlled clinical investigation in arthrosis. Pharmatherapeutica 1981; 2:504-508.
    7) Drovanti A, Bignamini AA, & Rovati AL: Therapeutic activity of oral glucosamine sulfate in osteoarthritis: a placebo-controlled double-blind investigation. Clin Ther 1980; 3:260-272.
    8) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    9) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    10) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    11) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    12) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    13) Higgins G: Optimistic look for disease modifiers in osteoarthritis. Inpharma 1993; 896:3-4.
    14) Ma L, Rudert WA, Harnaha J, et al: Immunosuppressive effects of glucosamine. J Biol Chem 2002; 277(42):39343-39349.
    15) McCarty MF: The neglect of glucosamine as a treatment for osteoarthritis - a personal perspective. Med Hypotheses 1994; 42:323-327.
    16) Mueller-Fassbender H, Bach GL, & Haase W: Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage 1994; 2:61-69.
    17) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    18) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    19) 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; 7:110-114.
    20) Qiu GX, Gao SN, & Giacovelli G: Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneim-Forsch/Drug Res 1998; 48:469-474.
    21) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 2001; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    22) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    23) Reichelt A, Forster KK, & Fischer M: Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee: a randomised, placebo-controlled, double-blind study. Arzneimittelforschung 1994; 44:75-80.
    24) Reuser AJJ & Wisselaar HA: An evaluation of the potential side-effects of alpha-glucosidase inhibitors used for the management of diabetes mellitus. Eur J Clin Invest 1994; 24(suppl 3):19-24.
    25) S Fabro : The Reproductive Toxicology Center (eds): REPROTOX (electronic version). Georgetown University Medical Center and Reproductive Toxicology Center, Columbia Hospital for Women Medical Center. Washington, DC (Internet Version). Edition expires Feb/28/1999; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    26) S Sweetman : Martindale: The Complete Drug Reference (electronic version). The Pharmaceutical Press. London, UK (Internet Version). Edition expires Feb/28/2002; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    27) Setnikar I, Palumbo R, & Canali S: Pharmacokinetics of glucosamine in man. Arzneimittelforschung 1993; 43:1109-1113.
    28) Tapadinhas MJ, Rivera IC, & Bignamini AA: Oral glucosamine sulphate in the management of arthrosis: report on a multi-centre open investigation in Portugal. Pharmatherapeutica 1982; 3:157-168.
    29) Vidal y Plana RR, Bizzarri D, & Rovati AL: Articular cartilage pharmacology. I. In vitro studies on glucosamine and non steroidal antiinflammatory drugs. Pharmacol Res Commun 1978; 10:557-569.
    30) Yoshikawa H, Tajiri Y, Sako Y, et al: Glucosamine-induced beta-cell dysfunction: a possible involvement of glucokinase or glucose-transporter type 2. Pancreas 2002; 24(3):228-234.
    31) da Camara CC & Dowless GV: Glucosamine sulfate for osteoarthritis. Ann Pharmacother 1998; 32:580-587.
    32) von Felden J, Montani M, Kessebohm K, et al: Drug-induced acute liver injury mimicking autoimmune hepatitis after intake of dietary supplements containing glucosamine and chondroitin sulfate. Int J Clin Pharmacol Ther 2013; 51(3):219-223.