InteractionsGuide Index Page
Analysis Search Terms:
Glucosamine Sulfate
Nutrient Name: Glucosamine sulfate.
Synonyms: Glucosamine sulphate;
Related Substances: Glucosamine hydrochloride, N-acetyl-
Chemistry
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 A
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-
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 of
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.
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.
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 B
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”:
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.
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