InteractionsGuide Index Page

 
Case Analysis Toolclose
Enter Each Substance:


Analysis Search Terms:

Glucosamine Sulfate

Nutrient Name: Glucosamine sulfate.
Synonyms: Glucosamine sulphate;D-glucosamine sulfate potassium salt; GS.
Related Substances: Glucosamine hydrochloride, N-acetyl-D-glucosamine (NAG, N-A-G).

Summary Table
nutrient description

Chemistry

D-Glucosamine (2-amino-2-deoxy-D-glucose) is a chemically defined, small molecule (molecular weight, 179.17 daltons) with a p Kaof 6.91. It is an amino-monosaccharide molecule, formed of glucose and an amine moiety, and one of the basic constituents of the disaccharidic units of articular cartilage glycosaminoglycans (GAGs). The amine is positively charged at physiologic pH and will hold a counter anion, either two chlorides or one sulfate.

See also Nutrient Preparations section.

Physiology and Function

Glucosamine plays a central role in determining the strength and resiliency of connective tissue. An amino sugar biosynthesized from glucose, glucosamine is one of the principal substrates used in the biosynthesis of macromolecules that comprise articular cartilage and thus a key compound within the ground substance that makes up connective tissue. Glucosamine is the preferred substrate for biosynthesis of mucopolysaccharides and bipolymers of the articulations and bones and has been reported to facilitate the hexosamine pathway of proteoglycan synthesis by the chondrocytes. It modulates interleukin-1 (IL-1)–induced activation of chondrocytes for cartilage rebuilding and stimulates production of proteoglycans (including therefore the proteic moiety) with a normal polymeric structure while simultaneously inhibiting proteoglycan degradation. Glucosamine also stimulates synthesis of GAGs and collagen, as well as synovial production of hyaluronic acid, which is critical to the lubricating and shock-absorbing properties of synovial fluid. Glucosamine sulfate (GS), in particular, can increase serum sulfate concentrations and thereby elevate synovial fluid sulfate concentrations and enable proteoglycan sulfation. 1 In addition to these nutritive and stimulating functions, GS also inhibits some cartilage-destroying enzymes, such as serine proteases collagenase and phospholipase A2(PLA2), and the generation of cell-damaging superoxide radicals. Thus, GS exerts a mild anti-inflammatory effect by a mechanism of action other than the inhibition of the biosynthesis of prostaglandins, most likely inhibition of proinflammatory effects of the nuclear factor kappa B (NF-κB) pathway.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Glucosamine (sulfate) is primarily used to relieve symptoms, stop disease progression, and stimulate joint cartilage growth in the treatment of osteoarthritis (OA). In this role, GS acts as chondroprotective agent by stopping the pathogenic mechanism of OA, relieving its symptoms, and reducing its progression. Surveys show that it is one of the most widely used nutraceuticals in self-medication practices, especially among the elderly population. 2 Most, 3-12but not all, 13 published studies, have shown positive effects on both joint pain and joint structure (e.g., joint space narrowing) in patients with OA, particularly of the knee, compared with nonsteroidal anti-inflammatory drugs (NSAIDs) or placebo. In addition to its beneficial activities on cartilage and chondrocytes, glucosamine has generally demonstrated mild anti-inflammatory properties and a favorable pharmacokinetic profile. Until recently, long-term studies on the effectiveness of GS have been lacking.

Historical/Ethnomedicine Precedent

No historical precedents have been reported.

Possible Uses

Cartilage injuries, gonarthritis, kidney stones, low back pain, minor injuries, osteoarthritis (OA), sprains and strains, temporomandibular joint (TMJ) dysfunction pain and joint noises, wound healing.

Deficiency Symptoms

There are no reports of a glucosamine deficiency, per se, in humans. The issue of sulfate deficiencies may deserve further attention.

Dietary Sources

Tempeh, a fermented soy product, is a food source of glucosamine. 14 However, significant amounts of glucosamine are not a normal constituent of most diets.

Nutrient Preparations Available

Commercially available glucosamine products are available in three forms. Glucosamine sulfate (GS) is the primary form used in clinical settings. However, many products labeled as “glucosamine” contain glucosamine hydrochloride. N-acetyl-D-glucosamine (NAG) is a related substance found in joints and connective tissue.

Glucosamine sulfate is the preferred form because of its very high absorption, ease of utilization, immediacy of incorporation into connective tissue matrix, and history of clinical studies. Sulfur is an essential nutrient for joint tissue, where it functions in the stabilization of the connective tissue matrix of cartilage, tendons, and ligaments. In particular, sulfation is an active metabolic process in cartilage, and the sulfate moiety seems to be essential to sulfation, an active metabolic process in cartilage. The sulfate moiety also seems to be essential to synovial fluid delivery to articular cartilage as well as improving efficacy of the synovial fluid by strengthening cartilage and aiding GAG synthesis. 3,15Further, even though it is often used in clinical trials, evidence supporting efficacy of the hydrochloride (HCl) salt of glucosamine is weak and unclear, and its use is rarely recommended by experienced clinicians. 16

Chitin is a polymer ofD-glucosamine with randomly assignedD-glucosamine monomers having a chemically bonded “acetyl” group, giving rise to NAG units. After extraction from the exoskeletons of shrimp and other shellfish, chitin can be chemically modified with hydrochloric acid digestion and deacetylation to yield quite pureD-glucosamine HCl monomers. Combining glucosamine HCl with sulfuric acid yields glucosamine sulfate. Glucosamine sulfate is produced through a co-crystallization step with sodium chloride (NaCl), resulting in a GS-NaCl complex. Alternatively, potassium chloride (KCl) can be used as the co-crystallization agent. Although most clinical trials have focused on the NaCl-stabilized form, the form using KCl as a stabilizer may be preferable for most individuals, given general dietary tendencies toward excess sodium and inadequate potassium intake. However, this issue has not yet been studied in controlled trials. In either form, these mineral salts stabilize GS by decreasing oxidation and moisture absorption.

In contrast, glucosamine HCl is typically granulated to reduce moisture absorption from the air. Salts are usually not necessary for its crystallization, but polyvinylpyrrolidone and corn syrup are often used as binders for granule formation. 17

Regarding the N-acetyl form of glucosamine, researchers have concluded that “glucosamine is a more efficient precursor of macromolecular hexosamine (glycosaminoglycans) than N-acetylglucosamine. It is possible that N-acetylglucosamine does not penetrate the cell membranes and, as a result, is not available for incorporation into glycoproteins and mucopolysaccharides.” 18 Further, clinical trials using NAG in the treatment of osteoarthritis are lacking.

Dosage Forms Available

Capsule, tablet, liquid, powder.

Source Materials for Nutrient Preparations

Supplemental glucosamine is usually derived from the processed exoskeletons of shellfish, such as shrimp, lobster, and crab. Glucosamine may also be synthesized. A novel source of the HCl form is fermented corn-derived glucose, although this may not be a preferred form.

Dosage Range

Adult

Dietary: Not appreciable.

Supplemental/Maintenance: Generally not considered as recommended on a preventive basis, but glucosamine is widely used by individuals with a history of or susceptibility to joint pain or injury.

Pharmacological/Therapeutic: 500 to 2000 mg daily, most often 500 mg three times daily (of GS) orally. Obese individuals may need to increase dosages by 20 mg/kg body weight daily. 19 Anecdotally, many clinicians experienced in treating pain and injuries with nutritional therapies report that doses at two to three times typical levels (i.e., 3000-4500 mg/day) for 3 to 5 days decreases pain and accelerates tissue repair immediately after injury.

Toxic: Glucosamine sulfate is generally considered nontoxic.

Pediatric (<18 Years)

Dietary: Not appreciable.

Supplemental/Maintenance: Not applicable.

Pharmacological/Therapeutic: Ehler-Danlos syndrome, Marfan syndrome.

Toxic: Glucosamine sulfate is generally considered nontoxic.

safety profile

Overview

In the majority of studies, oral GS at standard dosage levels appears to be safe, nontoxic, and well tolerated, with only minor, transient, and reversible adverse effects. Several studies have reported an incidence of adverse effects no greater than among subject receiving placebo. 4,10,20,21A meta-analysis by the Cochrane Collaboration reported only 16 adverse events requiring withdrawal from investigation, of 1000 patients treated for OA with glucosamine in 16 clinical trials. 22 Injectable and parenteral forms have also generally demonstrated an excellent safety profile. Allergic reactions appear to be rare and when suspected may derive from the shellfish used as source material for most preparations. 23

Nutrient Adverse Effects

General Adverse Effects

Rarely mild and transient gastrointestinal (GI) effects, including flatulence, abdominal bloating, indigestion, heartburn, nausea, and diarrhea. These symptoms are often reduced by taking GS with a meal.

Adverse Effects among Specific Populations

One study noted that the onset of possible adverse effects was significantly related to preexisting GI disorders and related treatments and to concomitant diuretic treatment. 20

One unqualified case report of impaired kidney function in a 79-year-old woman with myasthenia gravis, also undergoing corticosteroid and immunosuppressive therapy, resolved with discontinuation of glucosamine. 24

Pregnancy and Nursing

Although evidence or reports of adverse events associated with glucosamine administration during pregnancy or breastfeeding are lacking, no clinical studies have demonstrated safety in such populations.

Infants and Children

Evidence or reports of adverse events associated with glucosamine intake are lacking, but glucosamine administration is generally inappropriate for most children and should be avoided in those under 2 years of age.

Contraindications

None documented, with the exception of possible (and probably rare) allergic reactivity to shellfish.

Precautions and Warnings

Some individuals with preexisting peptic ulcers or other GI conditions may have increased susceptibility to adverse effects.

interactions review

Strategic Considerations

In general, comprehensive formal drug interaction studies involving glucosamine compounds are lacking. At this time, potential or suspected interactions involving diuretics or oral hypoglycemic agents appear to be discredited, clinically insignificant, or exceptional. A review of the scientific literature indicates that NSAIDs are the drug class most likely to manifest a clinically significant pattern of interaction with GS, and different agents within that class may theoretically produce different outcomes. Although evidence indicates that acetaminophen may obstruct the therapeutic activity of glucosamine, research is warranted to investigate opportunities for possible synergy or additive therapeutic benefit from coadministration with certain NSAIDs, such as ibuprofen.

Over the years, evidence supporting the clinical effectiveness of GS in the treatment of OA has increased in number, depth, and quality. Nevertheless, published clinical guidelines for integrative therapeutics involving glucosamine in the treatment of OA remain nascent and out of step with the clinical practices that have matured based on anecdotes, outcomes, and collective experience. At this point, the position of glucosamine as a potential first-line agent for repair of damaged or degenerating joint cartilage is reaching consensus level, at minimum for patients with knee OA who have mild to moderate pain. Ongoing and future studies of structure-modifying anti-OA drugs such as GS and chondroitin sulfate (CS) present the opportunity for further confirming the efficacy of these agents and clarifying appropriate therapeutic protocols customized to meet the needs of individuals and their variable life stages, personal history, genetic predispositions, diagnoses, and prognoses.

More fundamentally, the challenge of integrative medical care for OA will be to investigate, analyze, and synthesize the therapeutic strengths and opportunities presented by the range of treatment modalities. The therapeutic approach to integrative care of OA cannot rely solely on natural substances such as glucosamine alone or, for that matter, on any exclusively pharmacological approach. Other nutritional and botanical approaches, such as S-adenosylmethionine (SAMe), vitamin E, vitamin B3(niacinamide), bromelain, green-lipped mussel (Perna canaliculus), methylsulfonylmethane (MSM), cetyl myristoleate (CMO), topical capsaicin, turmeric (Curcuma longa), ginger (Zingiber officinale), devil's claw (Harpagophytum procumbens), boswellia (Boswellia serrata), and cat's claw (Uncaria tomentosa), are beginning to be studied in well-designed clinical trials, as are interventions such as aerobic exercise, quadriceps exercises, and footwear modification. Although the role of NSAIDs continues to undergo reformation in light of its limitations and adverse effects, new cyclooxygenase-2 (COX-2) inhibitors may have a role in situational symptom management in patients for whom simple analgesia is inadequate. Intra-articular hyaluronate injections may also have a limited role. Furthermore, the patient population appears receptive to medical and lifestyle interventions, such as weight reduction, yoga, tai qi, massage, acupuncture, and manipulative therapies, which are often beyond the realm of the average physician's training and experience, but which may be able to play an important role in restoring mobility and enhancing vitality within the context of an integrative therapeutic strategy.

Gottlieb 25 calls for a fundamental reevaluation of the medical view of OA and presents a perspective that remains challenging in its comprehensive approach in his 1997 review article, “Conservative management of spinal osteoarthritis with glucosamine sulfate and chiropractic treatment”: The rationales for using NSAIDs in the treatment of osteoarthritis is controversial and openly contested. Given the detrimental effects of NSAIDs on joints and other organs, their use should be discouraged and their classification as a first choice conservative treatment should be abolished. A truly effective and conservative approach to the treatment of osteoarthritis should include chiropractic manipulation [or other forms of joint mobilization and manipulation], essential nutrient supplementation, exogenous administration of glucosamine sulfate and rehabilitative stretches and exercises to maintain joint function. Because there is no correlation between pain levels and the extent of degeneration detected by radiographic or physical examination, conservative treatment should be initiated and sustained based on functional, objective findings and not strictly on how the patient feels. The use of NSAIDs should be limited to the treatment of gross inflammation and analgesics should only be used in the short-term when absolutely necessary for pain palliation. The present conservative approach could lead not only to a better quality of life but also to the saving of health care dollars by reducing the iatrogenic morbidity and mortality associated with NSAID use.

Thus, emerging approaches to treatment of OA may be prime ground for exploring the broad value, in terms of quality of life and meaningful outcomes standards, for multidisciplinary collaboration and integrative therapeutics.

nutrient-drug interactions
Acetaminophen, Ibuprofen, and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Acetaminophen (APAP, paracetamol; Tylenol); combination drugs: acetaminophen and codeine (Capital and Codeine; Phenaphen with Codeine; Tylenol with Codeine); acetaminophen and hydrocodone (Anexsia, Anodynos-DHC, Co-Gesic, Dolacet, DuoCet, Hydrocet, Hydrogesic, Hy-Phen, Lorcet 10/650, Lorcet-HD, Lorcet Plus, Lortab, Margesic H, Medipain 5, Norco, Stagesic, T-Gesic, Vicodin, Vicodin ES, Vicodin HP, Zydone); acetaminophen and oxycodone (Endocet, Percocet 2.5/325, Percocet 5/325, Percocet 7.5/500, Percocet 10/650, Roxicet 5/500, Roxilox, Tylox); acetaminophen and pentazocine (Talacen); acetaminophen and propoxyphene (Darvocet-N, Darvocet-N 100, Pronap-100, Propacet 100, Propoxacet-N, Wygesic); acetaminophen, butalbital, and caffeine (Fiorcet). COX-1 inhibitors (NSAIDs):Diclofenac (Cataflam, Voltaren), combination drug: diclofenac and misoprostol (Arthrotec), diflunisal (Dolobid), etodolac (Lodine), fenoprofen (Dalfon), furbiprofen (Ansaid), ibuprofen (Advil, Excedrin IB, Motrin, Motrin IB, Nuprin, Pedia Care Fever Drops, Provel, Rufen; combination drug: hydrocodone and ibuprofen (Reprexain, Vicoprofen), indomethacin (indometacin; Indocin, Indocin-SR), ketoprofen (Orudis, Oruvail), ketorolac (Acular ophthalmic, Toradol), meclofenamate (Meclomen), mefenamic acid (Ponstel), meloxicam (Mobic), nabumetone (Relafen), naproxen (Aleve, Anaprox, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), salsalate (salicylic acid; Amigesic, Disalcid, Marthritic, Mono Gesic, Salflex, Salsitab), sulindac (Clinoril), tolmetin (Tolectin). COX-2 inhibitor (NSAID):Celecoxib (Celebrex).
Drug-Induced Adverse Effect on Nutrient Function, Coadministration Therapeutic, with Professional Management
Adverse Drug Effect on Nutritional Therapeutics, Strategic Concern
Bimodal or Variable Interaction, with Professional Management
Beneficial or Supportive Interaction, with Professional Management

Probability: 3. Possible
Evidence Base: Preliminary

Effect and Mechanism of Action

Even when they temporarily relieve pain and reduce inflammation, NSAIDs may accelerate the progression of OA and similar connective tissue trauma, joint degeneration, or related disorders by promoting cartilage destruction and interfering with cartilage repair. However, this effect may vary among the different agents in this drug class. Glucosamine sulfate intake can significantly increase serum sulfate concentrations, required for GAG synthesis, and thereby elevate synovial fluid sulfate concentrations and enable proteoglycan sulfation. Acetaminophen metabolism involves sulfation and thus consumes the sulfate provided by GS and interferes with the therapeutic action of the nutrient. 1 Other NSAIDs appear to interact with GS to produce variable metabolic effects on the synovial environment and cartilage repair.

Research

Numerous in vivo, animal, and human studies suggest that many NSAIDs exert deleterious effects on synthesis of vasodilator prostaglandins, joint perfusion, chondrocyte and proteoglycan metabolism, cartilage synthesis, and organization in articular cartilage, especially influencing the course of OA. 26-32 Zupanets et al. 33 first investigated combining glucosamine and NSAIDs to determine if any resultant additive or synergistic effect might enable reduction of dosage levels necessary to obtain anti-inflammatory activity and thereby reduce adverse effects associated with these agents. They found that lower doses of voltaren, indomethacin, and piroxicam could be used in conjunction with glucosamine to reduce experimentally induced inflammation in mice and attributed these phenomena to a “diverse influence of aminosugar on the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs.” In unrelated but potentially significant research, Shikhman et al. 34 found that adding either glucosamine or NAG to human cartilage in vitro reduced inflammatory changes and gene expression induced by two different cytokines (interleukin 1β and tumor necrosis factor). This focus on the glucosamine led to, or at least paralleled, a focus on the respective roles and relative efficacy of the sulfate and hydrochloride forms and the mechanisms of NSAIDs’ apparent interference with healthy cartilage nutriture and repair.

In a study of the effect of glucosamine hydrochloride's effect on pain associated with OA of the knee, Houpt et al. 16 reported minimal efficacy in individuals concurrently taking up to 4000 mg acetaminophen daily. Interestingly, this and the GAIT studies are the primary published clinical trials involving glucosamine that are cited as lacking a beneficial outcome. Seeking to determine the relative importance of the sulfur component of GS, Hoffer et al. 1 and observed a significant increase in serum sulfate in subjects who received GS, versus sodium sulfate, after administering both compounds to healthy subjects, despite the elemental sulfate dose being doubled. The authors interpreted this increase in availability of sulfur compounds as critical to the delivery of critical nutrients to the synovium, which serves as the primary nutrient reservoir for cartilage that lacks significant direct blood supply. In particular, synovial fluid free sulfate appears to be essential to proteoglycan sulfation. These observations supported the researchers’ hypothesis that sulfate, rather than glucosamine, was the critical component of GS in its action on cartilage formation. In the second phase of this experiment, serum sulfate levels fell in those administered both acetaminophen and GS. Given that acetaminophen metabolism involves sulfation, these authors suggested that the drug consumed the sulfate provided by GS and would presumably blunt its nutritive effect on synovial fluid and therapeutic efficacy. Finally, they measured the serum and knee synovial fluid sulfate concentrations in OA patients and found virtually identical concentrations in both compartments, thus confirming the interrelationship of nutrient levels, particularly sulfate, between blood and synovial fluid. 1 Thus, in retrospect, questions arise as to whether the acetaminophen in the Houpt study may have interfered with the subjects’ obtaining the full measure of glucosamine's potential benefit and whether acetaminophen might interfere with the activity of glucosamine compounds by some mechanism other than affecting sulfation. Nevertheless, even in this study, as the authors noted: “After the end of the 8 week open label trial, 77% of the subjects were still taking glucosamine, although now obliged to pay for commercially available products.” 16

Subsequently, using a mouse model, Tallarida et al. 35 reported that commercial GS “administered as the sole agent (up to 500 mg/Kg, p.o.) was inactive in the mouse abdominal irritant test, but that certain combinations of glucosamine with nonopioid analgesics at the oral doses and ratios tested resulted in a synergistic (ibuprofen and ketoprofen), additive (diclofenac, indomethacin, naproxen, and piroxicam), or subadditive (aspirin and acetaminophen) antinociceptive interaction.” Examining specific fixed ratios of glucosamine and certain NSAIDs, they found that combinations containing racemic ibuprofen and glucosamine in greater than 1:1 ratio (glucosamine/ibuprofen) were synergistic in the test and that combinations of 2:1 and 9:1 yielded plasma levels of ibuprofen that were no different from administration of ibuprofen alone. These authors suggested that their findings supported further research into synergistic coadministration of GS and certain NSAIDs to enhance pain relief while reducing adverse effects usually associated with higher doses of NSAIDs. 35 Despite the continued use of glucosamine hydrochloride in major clinical trials, their concluding declaration that these findings were “being pursued in clinical trials” provides encouragement that important initial steps are being taken toward clarifying these significant findings and critically exploring such integrative therapeutic innovations.

Clinical research into the efficacy of glucosamine in the treatment of joint pain, inflammation, and degeneration has evolved to the point where opportunities for integrative therapeutic combinations are now ripe for systematic investigation. Although glucosamine and NSAIDs might appear superficially to contribute to the same therapeutic goals—relief of joint pain and degeneration—the evidence indicates that their respective mechanisms of action, character of effect, and role in strategic clinical management may result in either cooperative or antagonist influences and divergent outcomes, depending at least in part on the particular NSAID employed. One important factor in whether glucosamine (particularly GS) and individual NSAIDs potentiate or interfere with one another depends on the role of sulfation in each particular drug's metabolism. Research is still preliminary and large, well-designed clinical trials are clearly warranted. However, the findings thus far further suggest that those engaged in research design for studies of glucosamine's effect on OA or other forms of joint pain, as well as clinicians, should not allow subjects to use acetaminophen as a “rescue” drug, as has sometimes occurred in the past. Thus, heavier users of acetaminophen might derive less benefit from GS by diverting sulfate for drug metabolism, because acetaminophen is metabolized by multiple pathways, including sulfation.

Nutritional Therapeutics, Clinical Concerns, and Adaptations

In light of the accumulated and evolving evidence, concomitant use of glucosamine and particular NSAIDs appears to be a potentially valuable therapeutic option in the treatment of conditions for which both agents are typically used. However, based on both animal and human research, discrimination in selecting the most efficacious NSAID appears to be critical. Evidence suggests that coadministration of ibuprofen with GS may provide a synergistic therapeutic effect and that acetaminophen should be avoided. Such approaches, while novel and exploratory, appear to offer enhanced combined efficacy at minimal risk and cost and, because of the ability to reduce NSAID dosage levels, a likelihood of reduced risk of adverse effects. A reasonable option where the activity of an NSAID seems indicated might be combining the standard dosage of GS (500 mg) with ibuprofen (200 mg), three times daily, with phasing out of the ibuprofen to an as-needed basis when clinically improved. This long-term clinical strategy thus shifts from symptom management to maintenance, with emphasis on tissue strengthening and maximal restoration of healthy function.

theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Diuretics

Potassium-Sparing Diuretics:Amiloride (Midamor), spironolactone (Aldactone), triamterene (Dyrenium); combination drugs: amiloride and hydrochlorothiazide (Moduretic); spironolactone and hydrochlorothiazide (Aldactazide); triamterene and hydrochlorothiazide (Dyazide, Maxzide).

Loop Diuretics:Bumetanide (Bumex), ethacrynic acid (Edecrin), furosemide (Lasix), torsemide (Demadex).

Thiazide Diuretics:Bendroflumethiazide (bendrofluazide; Naturetin); combination drug: bendrofluazide and propranolol (Inderex); benzthiazide (Exna), chlorothiazide (Diuril), chlorthalidone (Hygroton), cyclopenthiazide (Navidrex); combination drug: cyclopenthiazide and oxprenolol hydrochloride (Trasidrex); hydrochlorothiazide (Aquazide, Esidrix, Ezide, Hydrocot, HydroDiuril, Microzide, Oretic); combination drugs: hydrochlorothiazide and amiloride (Moduretic); hydrochlorothiazide and captopril (Acezide, Capto-Co, Captozide, Co-Zidocapt); hydrochlorothiazide and enalapril (Vaseretic); hydrochlorothiazide and lisinopril (Prinzide, Zestoretic); hydrochlorothiazide and losartan (Hyzaar); hydrochlorothiazide and metoprolol (Lopressor HCT); hydrochlorothiazide and spironolactone (Aldactazide); hydrochlorothiazide and triamterene (Dyazide, Maxzide); hydroflumethiazide (Diucardin), methyclothiazide (Enduron), metolazone (Zaroxolyn, Mykrox), polythiazide (Renese), quinethazone (Hydromox), trichlormethiazide (Naqua).

Thiazide-like Diuretics:Indapamide (Lozol).

Glucosamine sulfate (GS) is stabilized with a mineral salt and consequently contains relatively high amounts of potassium chloride (KCl) or sodium chloride (NaCl). The action of diuretics on potassium may result in increased potassium levels or decreased effective levels of GS. Furthermore, individuals taking diuretics for hypertension, or otherwise on a sodium-restricted diet, may be adversely affected by the elevated sodium intake resulting from a glucosamine preparation stabilized with sodium. Likewise, individuals on a potassium-restricted diet may experience adverse effects from concomitant use of a diuretic and glucosamine stabilized with potassium. For example, in a product containing 300 mg GS per one tablet serving, a 12% potassium level (12%-13.5%) for source GS (potassium salt) would contain 36 mg potassium (36-41 mg). The proportion and amount of the sodium content in a sodium-based glucosamine salt would be comparable. 51 In other words, approximately 200 mg sodium or potassium, respectively, are included in a daily dose of 1500 mg GS.

Although the pharmacological rationale for this potential interaction between diuretics and glucosamine sulfate appears to be reasonable and well founded, evidence as to its clinical significance and any pattern of occurrence remains inadequate. In concluding their study of oral GS in the management of arthrosis, Tapadinhas et al. 20 noted that glucosamine administration was generally well tolerated, but adverse effects were significantly related to concomitant diuretic treatment, as well as to preexisting GI disorders and related treatments.

Physicians prescribing diuretics are advised to ask patients about their use of glucosamine (and other supplements) and to monitor blood pressure regularly and measure potassium levels as appropriate. Some individuals taking diuretics may need to take higher doses of glucosamine to obtain the full therapeutic effect, usually 20 mg/kg daily. 19 Daily fruit or other concomitant potassium may also be appropriate for individual on long-term therapy with potassium-depleting diuretics.

nutrient-drug interactions
Oral Hypoglycemic Agents and Insulin
nutrient-nutrient interactions
Bromelain
Chondroitin Sulfate
Manganese
Methylsulfonylmethane
Oligomeric Proanthocyanidins
Omega-3 Fatty Acids, Especially Fish Oils, Eicosapentaenoic Acid, and Docosahexanoic Acid
Vitamin C
Citations and Reference Literature
  • 1.Hoffer LJ, Kaplan LN, Hamadeh MJ et al. Sulfate could mediate the therapeutic effect of glucosamine sulfate. Metabolism 2001;50:767-770.View Abstract
  • 2.Blakeley JA, Ribeiro V. A survey of self-medication practices and perceived effectiveness of glucosamine products among older adults. Complement Ther Med 2002;10:154-160.
  • 3.Lopes Vaz A. 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;8:145-149.View Abstract
  • 4.Muller-Fassbender H, Bach GL, Haase W et al. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage 1994;2:61-69.View Abstract
  • 5.Noack W, Fischer M, Forster KK et al. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage 1994;2:51-59.View Abstract
  • 6.Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis: the role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Rheum Dis Clin North Am 1999;25:379-395.View Abstract
  • 7.Delafuente JC. Glucosamine in the treatment of osteoarthritis. Rheum Dis Clin North Am 2000;26:1-11, vii.View Abstract
  • 8.Towheed TE, Anastassiades TP, Shea B et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2001:CD002946.View Abstract
  • 9.Reginster JY, Deroisy R, Rovati LC et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001;357:251-256.View Abstract
  • 10.Pavelka K, Gatterova J, Olejarova M et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162:2113-2123.View Abstract
  • 11.Bruyere O, Honore A, Ethgen O et al. Correlation between radiographic severity of knee osteoarthritis and future disease progression: results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate. Osteoarthritis Cartilage 2003;11:1-5.
  • 12.Richy F, Bruyere O, Ethgen O et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003;163:1514-1522.View Abstract
  • 13.Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology (Oxford) 2002;41:279-284.View Abstract
  • 14.Sparringa RA, Owens JD. Glucosamine content of tempe mould, Rhizopus oligosporus. Int J Food Microbiol 1999;47:153-157.View Abstract
  • 15.Drovanti A, Bignamini AA, Rovati AL. Therapeutic activity of oral glucosamine sulfate in osteoarthrosis: a placebo-controlled double-blind investigation. Clin Ther 1980;3:260-272.View Abstract
  • 16.Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26:2423-2430.View Abstract
  • 17.Ebube NK, Mark W, Hahm H. Preformulation studies and characterization of proposed chondroprotective agents: glucosamine HCl and chondroitin sulfate. Pharm Dev Technol 2002;7:457-469.View Abstract
  • 18.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.View Abstract
  • 19.Murray MT. Encyclopedia of Nutritional Supplements. Rocklin, Calif: Prima Publishing; 1996.
  • 20.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.View Abstract
  • 21.Reginster JY, Henrotin Y, Pavelka K et al. Glucosamine sulfate (GS) is a specific osteoarthritis modifying drug: the results of two independent 3-year, randomized, controlled clinical trials. North American Menopause Society 12th Annual Meeting. New Orleans; 2001.
  • 22.Towheed TE. Published meta-analyses of pharmacological therapies for osteoarthritis. Osteoarthritis Cartilage 2002;10:836-837.View Abstract
  • 23.Matheu V, Gracia Bara MT, Pelta R et al. Immediate-hypersensitivity reaction to glucosamine sulfate. Allergy 1999;54:643.View Abstract
  • 24.Guillaume MP, Peretz A. Possible association between glucosamine treatment and renal toxicity: comment on the letter by Danao-Camara. Arthritis Rheum 2001;44:2943-2944.
  • 25.Gottlieb MS. Conservative management of spinal osteoarthritis with glucosamine sulfate and chiropractic treatment. J Manipulative Physiol Ther 1997;20:400-414.View Abstract
  • 26.Palmoski MJ, Brandt KD. Effects of some nonsteroidal antiinflammatory drugs on proteoglycan metabolism and organization in canine articular cartilage. Arthritis Rheum 1980;23:1010-1020.View Abstract
  • 27.Brooks PM, Potter SR, Buchanan WW. NSAID and osteoarthritis–help or hindrance? J Rheumatol 1982;9:3-5.
  • 28.Brandt KD. Effects of nonsteroidal anti-inflammatory drugs on chondrocyte metabolism in vitro and in vivo. Am J Med 1987;83:29-34.View Abstract
  • 29.Rashad S, Revell P, Hemingway A et al. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989;2:519-522.View Abstract
  • 30.Shield MJ. Anti-inflammatory drugs and their effects on cartilage synthesis and renal function. Eur J Rheumatol Inflamm 1993;13:7-16.View Abstract
  • 31.Cohen DB, Kawamura S, Ehteshami JR, Rodeo S. Traditional non-steroidal anti-inflammatory medications and cyclooxygenase-2 inhibitors impair rotator cuff tendon-to-bone healing. Annual Meeting of American Orthopaedic Society for Sports Medicine. Quebec City, Canada; 2004.
  • 32.Cohen DB, Kawamura S, Ehteshami JR, Rodeo SA. Indomethacin and celecoxib impair rotator cuff tendon-to-bone healing. Am J Sports Med 2006;34:362-369.View Abstract
  • 33.Zupanets IA, Drogovoz SM, Bezdetko NV et al. [The influence of glucosamine on the antiexudative effect of nonsteroidal anti-inflammatory agents]. Farmakol Toksikol 1991;54:61-63.View Abstract
  • 34.Shikhman AR, Kuhn K, Alaaeddine N, Lotz M. N-acetylglucosamine prevents IL-1β-mediated activation of human chondrocytes. J Immunol 2001;166:5155-5160.
  • 35.Tallarida RJ, Cowan A, Raffa RB. Antinociceptive synergy, additivity, and subadditivity with combinations of oral glucosamine plus nonopioid analgesics in mice. J Pharmacol Exp Ther 2003;307:699-704.View Abstract
  • 36.Balkan B, Dunning BE. Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats. Diabetes 1994;43:1173-1179.View Abstract
  • 37.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;96:132-140.View Abstract
  • 38.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;38:518-524.View Abstract
  • 39.Barzilai N, Hawkins M, Angelov I et al. Glucosamine-induced inhibition of liver glucokinase impairs the ability of hyperglycemia to suppress endogenous glucose production. Diabetes 1996;45:1329-1335.View Abstract
  • 40.Virkamaki A, Daniels MC, Hamalainen S et al. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance in multiple insulin sensitive tissues. Endocrinology 1997;138:2501-2507.View Abstract
  • 41.Shankar RR, Zhu JS, Baron AD. Glucosamine infusion in rats mimics the beta-cell dysfunction of non-insulin-dependent diabetes mellitus. Metabolism 1998;47:573-577.View Abstract
  • 42.Patti ME, Virkamaki A, Landaker EJ et al. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle. Diabetes 1999;48:1562-1571.View Abstract
  • 43.Virkamaki A, Yki-Jarvinen H. Allosteric regulation of glycogen synthase and hexokinase by glucosamine-6-phosphate during glucosamine-induced insulin resistance in skeletal muscle and heart. Diabetes 1999;48:1101-1107.
  • 44.Almada AL, Harvey PW, Platt KJ. Effect of chronic oral glucosamine sulfate upon fasting insulin resistance index (FIRI) in nondiabetic individuals. Program number 521.15. Experimental Biology 2000. San Diego; 2000.
  • 45.Uldry M, Ibberson M, Hosokawa M, Thorens B. GLUT2 is a high affinity glucosamine transporter. FEBS Lett 2002;524:199-203.
  • 46.Rovati LC, Annefeld M, Giacovelli G et al. Glucosamine in osteoarthritis. Lancet 1999;354:1640; author reply 1641-1642.View Abstract
  • 47.Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med 2003;163:1587-1590.View Abstract
  • 48.Reginster JY et al. Glucosamine sulfate significantly reduces progression of knee osteoarthritis over 3 years: a large, randomized, double-blind placebo-controlled prospective trial. American College of Rheumatology, Association of Rheumatology Health Professionals, 1999 Annual Scientific Meeting. Boston; 1999.
  • 49.Pouwels MJ, Jacobs JR, Span PN et al. Short-term glucosamine infusion does not affect insulin sensitivity in humans. J Clin Endocrinol Metab 2001;86:2099-2103.
  • 50.Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilage 2004;12:506-511.View Abstract
  • 51.McKee DL. Personal communication, 2003.
  • 52.Shankland WE 2nd. The effects of glucosamine and chondroitin sulfate on osteoarthritis of the TMJ: a preliminary report of 50 patients. Cranio 1998;16:230-235.View Abstract
  • 53.Leffler CT, Philippi AF, Leffler SG et al. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med 1999;164:85-91.View Abstract
  • 54.Lippiello L, Woodward J, Karpman R, Hammad TA. In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop 2000:229-240.View Abstract
  • 55.Das A Jr, Hammad TA. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis Cartilage 2000;8:343-350.
  • 56.Denham AC, Newton WP. Are glucosamine and chondroitin effective in treating osteoarthritis? J Fam Pract 2000;49:571-572.
  • 57.Reginster JY, Bruyere O, Lecart MP, Henrotin Y. Naturocetic (glucosamine and chondroitin sulfate) compounds as structure-modifying drugs in the treatment of osteoarthritis. Curr Opin Rheumatol 2003;15:651-655.View Abstract
  • 58.Cohen M, Wolfe R, Mai T, Lewis D. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol 2003;30:523-528.View Abstract
  • 59.Clegg DO, Reda DJ, Harris CL et al. The efficacy of glucosamine and chondroitin sulfate in patients with painful knee osteoarthritis (OA): the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT). American College of Rheumatology Meeting. San Diego; 2005.
  • 60.Clegg DO, Reda DJ, Harris CL et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-808.View Abstract
  • 61.Barnhill JG, Fye CL, Williams DW et al. Chondroitin product selection for the glucosamine/chondroitin arthritis intervention trial. J Am Pharm Assoc (Wash DC) 2006;46:14-24.View Abstract
  • 62.Hunter DJ, Zhang YQ, Niu JB et al. The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis. Arthritis Rheum 2006;54:795-801.View Abstract
  • 63.Usha PR, Naidu MUR. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest 2004;24:353-363.
  • 64.Kuttan R, Donnelly PV, Di Ferrante N. Collagen treated with (+)-catechin becomes resistant to the action of mammalian collagenase. Experientia 1981;37:221-223.View Abstract
  • 65.Vinciguerra G, Belcaro G, Cesarone MR et al. Cramps and muscular pain: prevention with Pycnogenol in normal subjects, venous patients, athletes, claudicants and in diabetic microangiopathy. Angiology 2006;57:331-339.View Abstract
  • 66.McCarty MF. Glucosamine for psoriasis? Med Hypotheses 1997;48:437-441.
  • .Adebowale AO, Cox DS, Liang Z, et al. Analysis of glucosamine and chondroitin sulfate content in marketed products and the caco-2 permeability of chondroitin sulfate raw materials. J Am Nutraceutical Assoc 2000;3:37-44.
  • .Adams ME. Target tissue models: cartilage changes in experimental osteoarthritis in the dog. J Rheumatol Suppl 1983;11:111-113.
  • .Ajiboye R, Harding JJ. The non-enzymic glycosylation of bovine lens proteins by glucosamine and its inhibition by aspirin, ibuprofen and glutathione. Exp Eye Res 1989;49(1):31-41.
  • .Baggio B, Gambaro G, Marzaro G, et al. Effects of the oral administration of glycosaminoglycans on cellular abnormalities associated with idiopathic calcium oxalate nephrolithiasis. Eur J Clin Pharmacol 1991;40(3):237-240.
  • .Barclay TS, Tsourounis C, McCart GM. Glucosamine. Ann Pharmacother 1998;32(5):574-579.
  • .Biggee BA, McAlindon T. Glucosamine for osteoarthritis: part I, review of the clinical evidence. Med Health R I 2004;87(6):176-179. (Review)
  • .Biggee BA, McAlindon T. Glucosamine for osteoarthritis: part II, biologic and metabolic controversies. Med Health R I 2004;87(6):180-181. (Review)
  • .Brandt KD. Non-surgical treatment of osteoarthritis: a half century of “advances.” Ann Rheum Dis 2004;63(2):117-122. (Review)
  • .Brief AA, Maurer SG, Di Cesare PE. Use of glucosamine and chondroitin sulfate in the management of osteoarthritis. J Am Acad Orthop Surg 2001;9(2):71-78. (Review)
  • .Bruyere O, Pavelka K, Rovati LC, et al. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause 2004;11(2):138-143.
  • .Chalmers R. Managing osteoarthritis of the knee: glucosamine-chondroitin should be prescribed by doctors. BMJ 2005;330(7492):673. (Letter)
  • .Christgau S, Henrotin Y, Tanko LB, et al. Osteoarthritic patients with high cartilage turnover show increased responsiveness to the cartilage protecting effects of glucosamine sulphate. Clin Exp Rheumatol 2004;22(1):36-42.
  • .Cibere J, Kopec JA, Thorne A, et al. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Rheum 2004;51(5):738-745.
  • .Clegg DO, Reda DJ, Harris CL, et al, for the GAIT Investigators. The efficacy of glucosamine and chondroitin sulfate in patients with painful knee osteoarthritis (OA): the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT). Plenary session, American College of Rheumatology (ACR) Meeting. San Diego, Nov 14, 2005.
  • .Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-808.
  • .Cohen M, Wolfe R, Mai T, et al. A randomised, double-blind, placebo-controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate and camphor for osteoarthritis of the knee. J Rheumatol 2003;30:523-528.
  • .Creamer P. Osteoarthritis pain and its treatment. Curr Opin Rheumatol 2000;12(5):450-455. (Review)
  • .Crolle G, D’Este E. Glucosamine sulphate for the management of arthrosis: a controlled clinical investigation. Curr Med Res Opin 1980;7(2):104-109.
  • .Curtis CL, Harwood JL, Dent CM, et al. Biological basis for the benefit of nutraceutical supplementation in arthritis. Drug Discov Today 2004;9(4):165-172. Erratum in Drug Discov Today 2004;9(7):336. (Review)
  • .da Camara CC, Dowless GV. Glucosamine sulfate for osteoarthritis. Ann Pharmacother 1998;32(5):580-587. (Review)
  • .D’Ambrosio E, Casa B, Bompani R, et al. Glucosamine sulphate: a controlled clinical investigation in arthrosis. Pharmatherapeutica 1981;2(8):504-508.
  • .Danao-Camara T. Potential side effects of treatment with glucosamine and chondroitin. Arthritis Rheum 2000;43(12):2853.
  • .Das A Jr, Hammad TA. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis Cartilage 2000;8(5):343-350.
  • .Denham AC, Newton WP. Are glucosamine and chondroitin effective in treating osteoarthritis? J Fam Pract 2000;49(6):571-572.
  • .Einhorn TA. If it feels good, do it: use of glucosamine sulfate to prevent the progression of osteoarthritis in postmenopausal women. Menopause 2004;11(2):134-135. (Editorial)
  • .Felson DT. Osteoarthritis of the knee. N Engl J Med 2006;354:841-848.
  • .Forster KK, Schmid K, Rovati LC, et al. Longer-term treatment of mild-to-moderate osteoarthritis of the knee with glucosamine sulfate: a randomized, controlled, double-blind clinical study. Eur J Clin Pharmacol 1996;50(6):542. (Abstract)
  • .Franci B, Campagna S, Battisti E, et al. The efficacy and safety of glucosamine sulfate in the treatment of gonarthritis. Clin Ter 1996;147(3):99-105.
  • .Giordano N, Nardi P, Senesi M, et al. [The efficacy and safety of glucosamine sulfate in the treatment of gonarthritis.] Clin Ter 1996;147(3):99-105. [Italian]
  • .Gottlieb MS. Conservative management of spinal osteoarthritis with glucosamine sulfate and chiropractic treatment. J Manipulative Physiol Ther 1997;20(6):400-414.
  • .Gaby AR. Natural treatments for osteoarthritis. Altern Med Rev 1999;4(5):330-341. (Review)
  • .Grainger R, Cicuttini FM. Medical management of osteoarthritis of the knee and hip joints. Med J Aust 2004;180(5):232-236. (Review)
  • .Heart E, Sung CK. Glucose transport by osmotic shock and vanadate is impaired by glucosamine. Biochem Biophys Res Commun 2002;292(2):308-311.
  • .Hellio MP, et al. The effects of glucosamine on human chondrocyte gene expression. Madrid: The Ninth Eular Symposium; 1996:11-12.
  • .Herrero-Beaumont G. Glucosamine Unum In Die [Once A Day] Efficacy (GUIDE) Trial: glucosamine sulfate in patients with knee osteoarthritis. American College of Rheumatology (ACR) Meeting. San Diego, Nov 15, 2005.
  • .Hochberg MC. Nutritional supplements for knee osteoarthritis: still no resolution. N Engl J Med 2006;354:858-860. (Editorial)
  • .Hochberg MC. What a difference a year makes: reflections on the ACR recommendations for the medical management of osteoarthritis. Curr Rheumatol Rep 2001;3(6):473-478. (Review)
  • .Hochberg MC, Dougados M. Pharmacological therapy of osteoarthritis. Best Pract Res Clin Rheumatol 2001;15(4):583-593. (Review)
  • .Hoffer LJ, Kaplan LN, Hamadeh MJ, et al. Sulfate could mediate the therapeutic effect of glucosamine sulfate. Metabolism 2001;50(7):767-770.
  • .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(1):106-111.
  • .Houpt JB, McMillan R, Wein C, et al. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26(11):2423-2430.
  • .Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology (Oxf) 2002;41(3):279-284.
  • .Hughes RA, Chertsey AJ. A randomised, double-blind, placebo-controlled trial of glucosamine to control pain in osteoarthritis of the knee. Arthritis Rheum 2000;43(9 suppl):S384. (Abstract)
  • .Hungerford DS, Jones LC. Glucosamine and chondroitin sulfate are effective in the management of osteoarthritis. J Arthroplasty 2003;18(3 Suppl 1):5-9. (Review)
  • .Hunter DJ, Zhang YQ, Niu JB, et al. The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis. Arthritis Rheum 2006;54(3):795-801.
  • .Jiminez SA, et al. The effects of glucosamine on human chondrocyte gene expression. Madrid: The Ninth Eular Symposium; 1996;8-10.
  • .Jimenez SA, Dodge GR. The effects of glucosamine sulfate (GSO4) on human chondrocyte gene expression. Osteoarthritis Cartilage 1997;5:72. (Abstract)
  • .Karzel K, Domenjoz R. Effects of hexosamine derivatives and uronic acid derivatives on glycosaminoglycane metabolism of fibroblast cultures. Pharmacology 1971;5(6):337-345.
  • .Kelly GS. The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Altern Med Rev 1998;3(1):27-39. (Review)
  • .Kohn P, Winzler RJ, Hoffman RC. Metabolism of D-glucosamine and N-acetyl-D-glucosamine in the intact rat. J Biol Chem 1962;237:304-308.
  • .Kreder HJ. Glucosamine and chondroitin were found to improve outcomes in patients with osteoarthritis. J Bone Joint Surg Am 2000;82(9):1323.
  • .Laferrere B, Garcia-Lorda P, Russell CD, et al. Effect of oral glucosamine sulfate on serum leptin levels in human subjects. Nutrition 2004;20(3):321-322.
  • .Leffler CT, Philippi AF, Leffler SG, et al. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med 1999;164(2):85-91.
  • .Lequesne M, Brandt K, Bellamy N, et al. Guidelines for testing slow acting drugs in osteoarthritis. J Rheumatol Suppl 1994;41:65-73. Erratum in J Rheumatol Suppl 1994;21(12):2395.
  • .Levin RM, Krieger NN, Winzler RJ. Glucosamine and acetylglucosamine tolerance in man. J Lab Clin Med 1961;58(6):927-932.
  • .Lippiello L, et al. Beneficial effect of cartilage disease-modifying agents tested in chondrocyte cultures and a rabbit instability model of osteoarthritis. American College of Rheumatology, Association of Rheumatology Health Professionals, 1999 Annual Scientific Meeting. Boston, Nov 15, 1999.
  • .Lippiello L, Woodward J, Karpman R, et al. In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop 2000;(381):229-240.
  • .Matheson AJ, Perry CM. Glucosamine: a review of its use in the management of osteoarthritis. Drugs Aging 2003;20(14):1041-1060.
  • .McAlindon T. Glucosamine and chondroitin for osteoarthritis? Bull Rheum Dis 2001;50(7):1-4. (Review)
  • .McAlindon TE, Biggee BA. Nutritional factors and osteoarthritis: recent developments. Curr Opin Rheumatol 2005;17(5):647-652. (Review)
  • .McAlindon T, Formica M, LaValley M, et al. Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med 2004;117(9):643-649.
  • .McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283(11):1469-1475.
  • .McCarty MF. Enhanced synovial production of hyaluronic acid may explain rapid clinical response to high-dose glucosamine osteoarthritis. Med Hypothes 1998;50:507-510.
  • .McCarty MF. Glucosamine may retard atherogenesis by promoting endothelial production of heparin sulfate proteoglycans. Med Hypotheses 1997;48(3):245-251.
  • .McCarty MF. Glucosamine for wound healing. Med Hypotheses 1996;47(4):273-275.
  • .McCarty MF. The neglect of glucosamine as a treatment for osteoarthritis, a personal perspective. Med Hypotheses 1994;42:323-327.
  • .Menzel EJ. [Polymeric chondroitin sulfate vs. monomeric glucosamine for the treatment of osteoarthritis.] Wien Med Wochenschr 2000;150(5):87-90. [German] (Review)
  • .Miller CA. Newer and safer options for osteoarthritis. Geriatr Nurs 2001;22(3):165-166.
  • .Monauni T, Zenti MG, Cretti A, et al. Effects of glucosamine infusion on insulin secretion and insulin action in humans. Diabetes 2000;49(6):926-935.
  • .Murray MT. Encyclopedia of nutritional supplements. Rocklin, CA: Prima Publishing; 1996.
  • .Murray MT. Which is better: aged versus fresh garlic; glucosamine sulfate versus chondroitin sulfate. Am J Natural Med 1997;4:5-8.
  • .Nguyen P, Mohamed SE, Gardiner D, et al. A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: a pilot study. Cranio 2001;19(2):130-139.
  • .Noack W, Fischer M, Forster KK, et al. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage 1994;2(1):51-59.
  • .Nowlan C, Wetmore S. Short report: ibuprofen versus glucosamine sulfate: treating osteoarthritis pain. Can Fam Physician 2003;49:1632-1634.
  • .Noyszewski EA, Wroblewski K, Dodge GR, et al. Preferential incorporation of glucosamine into the galactosamine moieties of chondroitin sulfates in articular cartilage explants. Arthritis Rheum 2001;44(5):1089-1095.
  • .Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate decreases progression of knee osteoarthritis in a long-term randomized placebo-controlled, independent, confirmatory trial. Arthritis Rheum 2000;43(9 Suppl):S384.
  • .Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162(18):2113-2123.
  • .Piperno M, Reboul P, Hellio Le Graverand MP, et al. Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro. Osteoarthritis Cartilage 2000;8(3):207-212.
  • .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(2):110-114.
  • .Qiu GX, Gao SN, Giacovelli G, et al. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung 1998;48(5):469-474.
  • .Rashad S, Revell P, Hemingway A, et al. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989;2(8662):519-522.
  • .Rao JK, Mihaliak K, Kroenke K, et al. Use of complementary therapies for arthritis among patients of rheumatologists. Ann Intern Med 1999;131(6):409-416.
  • .Reginster JY. Review: glucosamine and chondroitin improve outcomes in osteoarthritis, but the magnitude of effect is unclear. ACP J Club 2000;133:58. (Review)
  • .Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001;357(9252):251-256.
  • .Reginster JY, Henrotin Y, Pavelka K, et al. Glucosamine sulfate (GS) is a specific osteoarthritis modifying drug: the results of two independent 3-year, randomized, controlled clinical trials. North American Menopause Society 12th Annual Meeting. New Orleans, Oct 4-6, 2001. (Abstract)
  • .Reichelt A, Forster KK, Fischer M, et al. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee: a randomised, placebo-controlled, double- blind study. Arzneimittelforschung 1994;44(1):75-80.
  • .Reijman M, Bierma-Zeinstra SM, Pols HA, et al. Is there an association between the use of different types of nonsteroidal antiinflammatory drugs and radiologic progression of osteoarthritis? The Rotterdam Study. Arthritis Rheum 2005;52(10):3137-3142.
  • .Richy F, Bruyere O, Ethgen O, et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003;163(13):1514-1522.
  • .Rindone JP, Hiller D, Collacott E, et al. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med 2000;172(2):91-94.
  • .Rovati LC, Giacovelli G, Annefeld M, et al. A large, randomised, placebo controlled, double-blind study of glucosamine sulfate vs. piroxicam and vs. their association, on the kinetics of the symptomatic effect in knee osteoarthritis. Osteoarthritis Cartilage 1994;2(Suppl 1):56. (Abstract)
  • .Ruane R, Griffiths P. Glucosamine therapy compared to ibuprofen for joint pain. Br J Community Nurs 2002;7(3):148-152. (Review)
  • .Russell AI, McCarty MF. Glucosamine in osteoarthritis. Lancet 1999;354:1641-1642. (Letter)
  • .Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther 2000;14(12):1567-1579.
  • .Scheen AJ, Lefebvre PJ. Potential pharmacokinetics interference between alpha-glucosidase inhibitors and other oral antidiabetic agents. Diabetes Care 2002;25(1):247-248.
  • .Setnikar I. Antireactive properties of "chondroprotective" drugs. Int J Tissue React 1992;14(5):253-261.
  • .Setnikar I, Cereda R, Pacini MA, et al. Antireactive properties of glucosamine sulfate. Arzneimittelforschung 1991;41(2):157-161.
  • .Setnikar I, Giacchetti C, Zanolo G. Pharmacokinetics of glucosamine in the dog and in man. Arzneimittelforschung 1986;36(4):729-735.
  • .Setnikar I, Pacini MA, Revel L. Antiarthritic effects of glucosamine sulfate studied in animal models. Arzneimittelforschung 1991;41(5):542-545.
  • .Setnikar I, Rovati LC. Absorption, distribution, metabolism and excretion of glucosamine sulfate: a review. Arzneimittelforschung 2001;51(9):699-725. (Review)
  • .Setnikar I, Palumbo R, Canali S, et al. Pharmacokinetics of glucosamine in man. Arzneimittelforschung 1993;43:1109-1113.
  • .Shankland WE II. The effects of glucosamine and chondroitin sulfate on osteoarthritis of the TMJ: a preliminary report of 50 patients. Cranio 1998;16(4):230-235.
  • .Swinburne LM. Glucosamine sulphate and osteoarthritis. Lancet 2001;357(9268):1617.
  • .Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilage 2004;12(6):506-511.
  • .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(6):1347-1355.
  • .Towheed TE, Anastassiades TP. Glucosamine and chondroitin for treating symptoms of osteoarthritis: evidence is widely touted but incomplete. JAMA 2000;283(11):1483-1484.
  • .Towheed TE, Anastassiades TP. Glucosamine therapy for osteoarthritis. J Rheumatol 1999;26(11):2294-2297.
  • .Towheed TE, Anastassiades TP, Shea B, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2001(1):CD002946.
  • .Vacha J, Pesakova V, Krajickova J, et al. Effect of glycosaminoglycan polysulphate on the metabolism of cartilage ribonucleic acid. Arzneimittelforschung 1984;34(5):607-609.
  • .Vajaradul Y. Double-blind clinical evaluation of intra-articular glucosamine in outpatients with gonarthrosis. Clin Ther 1981;3(5):336-343.
  • .Vajranetra P. Clinical trial of glucosamine compounds for osteoarthrosis of knee joints. J Med Assoc Thai 1984;67(7):409-418.
  • .van Blitterswijk WJ, van de Nes JC, Wuisman PI. Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: biochemical rationale and case report. BMC Complement Altern Med 2003;3(1):2.
  • .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(6):557-569.
  • .Walker-Bone K. ‘Natural remedies’ in the treatment of osteoarthritis. Drugs Aging 2003;20(7):517-526. (Review)
  • .Weiden S, Wood IJ. The fate of glucosamine hydrochloride injected intravenously in man. J Clin Pathol 1958;11:343-349.
  • .Weimann G, Lubenow N, Selleng K, et al. Glucosamine sulfate does not crossreact with the antibodies of patients with heparin-induced thrombocytopenia. Eur J Haematol 2001;66(3):195-199.
  • .Wein CR, Houpt JB, McMillan R, et al. Open trial of glucosamine hydrochloride (GHCl) in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1998;25(Suppl 52):8.
  • .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.