Glucosamine
Glucosamine: Not helpful, can be harmful with Dr Mark Donohoe and Andrew Whitfield-Cook
- Glucosamine may have a limited effect, more likely in older patients who have arthritis that is more severe or when used for longer periods of time.
- Glucosamine may take longer to act than NSAIDs, but once it does, its effects may last longer after treatment is stopped.
- Although European treatment guidelines recommend a prescription formulation, this product is not available in the US and other guidelines generally do not recommend glucosamine for OA conditions.
- Glucosamine has not been found effective in relieving back pain.
Caution: The results of one trial suggest that patients on diuretics might need to take higher doses of glucosamine for full effect.
Glucosamine may increase the effects of antidiabetics (theoretical). A popular treatment for arthritis includes the administration of chondroitin sulfate and N-acetylglucosamine. If the arthritis is Lyme-induced, N-acetylglucosamine is contraindicated as it feeds Borrelia Burgdorferi.
Clinical Summary:
Glucosamine is an endogenous aminomonosaccharide synthesized from glucose. Found in mucopolysaccharides, mucoproteins and chitin, a cellulose-like biopolymer in marine invertebrate exoskeletons, it is used in the biosynthesis of proteoglycans and glycosaminoglycans, which are sugarprotein molecules found in cartilage. Glucosamine has anti-inflammatory activity, and is marketed as a dietary supplement and often paired with chondroitin sulfate for joint health.
Glucosamine has been mostly studied for osteoarthritis (OA) conditions. Although glucosamine/chondroitin supplementation was comparable to celecoxib in a large multicenter trial of patients with severe knee OA pain , other studies have not found benefit with glucosamine, chondroitin, or the combination for knee or hip OA . Data on chondroitin alone also suggest no significant benefit . In addition, no efficacy was seen with glucosamine in relieving back pain , degenerative lumbar OA , or improving glucose metabolism in type 2 diabetes . Any benefits with glucosamine may be limited to older patients who have arthritis that is more severe or for longer periods of time .
Meta-analyses of glucosamine trials are also somewhat mixed . The American College of Rheumatology (ACR) conditionally recommends that patients avoid glucosamine for osteoarthritis . In contrast, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment guidelines recommends a prescription glucosamine formulation as being superior to other forms, but this product is not available in the US . It is further suggested that these differences in availability and formulas have contributed to the lack of significant effect across studies and pooled analyses .
Studies on whether glucosamine can improve temporomandibular joint (TMJ) symptoms are limited and generally provide only low evidence of this effect , although one study of oral glucosamine adjunctive to hyaluronic acid injection suggests long-term benefit. Epidemiological studies suggest potential reduction for some cancer risks and mortality with long-term glucosamine/chondroitin supplementation, although limitations such as bias could not be ruled out and confirmatory studies are needed .
There are case reports of liver injury/toxicity related to glucosamine consumption . Patients on antiplatelet or anticoagulant therapies should be monitored for interactions or increased INR levels . Patients with poorly controlled diabetes or glucose intolerance should be monitored as glucosamine could worsen insulin resistance.
Mechanism of Action
Progressive degeneration of cartilage glycosaminoglycans is evident in osteoarthritis. Glucosamine is the first step in glycosaminoglycan biosynthesis. In vitro, it increased production of monomeric proteoglycans capable of assembling into high molecular weight aggregates . Glucosamine can protect cartilage from metabolic impairment by NSAIDs, corticosteroids, and by exerting anti-inflammatory effects . It may promote cartilage repair by inducing tissue TGFβ1 and CTGF expression that regulates chondrocyte proliferation . Long-term reductions in TMJ symptoms with adjunctive oral glucosamine may be due to TGF-beta stimulation and IL-1beta / IL-6 suppression . Reduced systemic inflammation and cytokine activity found in a small randomized crossover study may explain potential reductions in mortality or cancer risk .
Although glucosamine is slow to act , its effects may persist after treatment cessation .
The rise in intraocular pressure associated with older patients in one study may relate to exogenous glycosaminoglycans effects on accumulations of extracellular matrix and thickening of the basement membrane, thereby compromising function of the trabecular meshwork.
Cautions
Patients with liver disease should avoid taking glucosamine, as it is extensively metabolized in the liver and there are case reports of liver injury/toxicity.
Patients who are taking anticoagulants or antiplatelet drugs or who have glaucoma or diabetes should be monitored, as there is some preliminary evidence for potential side effects.
Adverse Reactions:
Glucosamine tends to be safe and well tolerated , but caution should be exercised in certain populations
Rare reactions include gastrointestinal complaints and allergic reactions .
Case Reports
Chronic tubulointerstitial nephropathy: In a 67-year-old patient who took glucosamine daily for 3 years for
OA knee pain .
Increased intraocular pressure: In a randomized double-blind trial, glucosamine sulfate supplementation
significantly increased intraocular pressure in older patients with OA . The implication of this finding
needs further evaluation.
Liver injury/hepatotoxicity and elevated aminotransferase values: In patients with liver disease .
Reduced glucose tolerance: From infusion and oral forms of glucosamine
Drug Interactions
Warfarin: Although more information is needed to define this interaction, glucosamine-chondroitin
may potentiate warfarin effects and increase INR levels.
Anticoagulants/Antiplatelets: Use of glucosamine may inhibit platelet aggregation
Lab Interactions
Blood glucose levels: May be affected by glucosamine.
Increased International Normalized Ratio (INR): Glucosamine was associated with increased INR that
return to normal levels when discontinued.
Elevated aminotransferase values: In patients with liver disease