- Glucosamine sulphate
- Glucosamine hydrochloride
For Patients & Caregivers
How It Works
Conclusive evidence is lacking to support the effectiveness of glucosamine against arthritis.
Cartilage is composed of collagen, elastin, and sugar-protein molecules, that make it gel-like, resilient, and act as a shock absorber. Osteoarthritis is characterized by progressive cartilage degeneration. Glucosamine may help with formation of the sugar-protein molecules, which would slow the degeneration of cartilage. However, clinical trials yielded mixed results. Glucosamine may reduce inflammation and protect cartilage from damage caused by NSAIDs and corticosteroids, but additional studies are needed. In addition, the American College of Rheumatology (ACR) conditionally recommends that patients avoid glucosamine for osteoarthritis.
To reduce inflammation
Glucosamine may reduce inflammation in a way that is different from non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen.
To prevent osteoarthritis and treat disease progression
Several clinical trials of glucosamine alone and in combination with chondroitin sulfate yielded mixed results. The differences in availability of formulas may also contribute to the lack of significant effect across studies and pooled analyses.
To treat temporomandibular joint disorder (TMJ)
There is limited evidence to suggest glucosamine may be help for TMJ symptoms. Additional studies are needed.
- Patients with liver disease should avoid taking glucosamine, as there are case reports of liver injury/toxicity.
- Patients who are taking blood-thinners or who have glaucoma or diabetes should tell their healthcare professionals if they are taking glucosamine. There is some preliminary evidence for potential side effects and related monitoring needs should be discussed.
Do Not Take If
Glucosamine tends to be safe and well tolerated, but caution should be exercised in certain populations (see Warnings and Interactions). Rare reactions include gastrointestinal complaints and allergic reactions.
- Kidney problems: In a 67-year-old patient with long-term use of glucosamine.
- Increased warfarin effects or INR levels (related to blood-thinning medication monitoring): Occurred with glucosamine-chondroitin; lab tests returned to normal levels when glucosamine was discontinued.
- Liver injury/toxicity and elevated lab values: In patients with liver disease.
- Increased fluid pressure inside the eye: In older patients with osteoarthritis who took glucosamine supplements in a study. The meaning of this finding needs further evaluation.
- Reduced glucose tolerance: From infusion and oral forms of glucosamine.
- Analysis of 366 adverse drug reactions to glucosamine and chondroitin preparations showed 263 cases had hypersensitivity reactions. These included mild (eg, pruritus, urticaria and lip oedema); moderate (such as dyspnoea, nausea and abdominal pain); and severe (including amnesia, gait disturbance, somnolence and hypotension).
- 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.
For Healthcare Professionals
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 sugar-protein molecules found in cartilage. Glucosamine has anti-inflammatory effects, and is marketed as a dietary supplement and often paired with chondroitin sulfate for joint health.
Glucosamine has been mostly studied for osteoarthritis (OA). Although glucosamine/chondroitin supplementation was comparable to celecoxib in a large multicenter trial of patients with severe knee OA pain (2), and supplementation shown to reduce circulating inflammatory cytokine IL-6 (47), other studies have not found benefit with glucosamine, chondroitin, or the combination for knee or hip OA (3) (4) (5) (6) (7) (8) (9) (10). Data on chondroitin alone also suggest no significant benefit (10) (11). In addition, no efficacy was seen with glucosamine in relieving back pain (12) (13), degenerative lumbar OA (13), or improving glucose metabolism in type 2 diabetes (14). Any benefits with glucosamine may be limited to older patients who have arthritis that is more severe (15) or for longer periods of time (16).
Meta-analyses of glucosamine trials are also mixed (35) (36) (37) (38) (39). The American College of Rheumatology (ACR) conditionally recommends that patients avoid glucosamine for osteoarthritis (45). In contrast, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment guidelines (40) recommend a prescription glucosamine formulation as being superior to other forms, but this product is not available in the US (40). It is further suggested that these differences in availability and formulas have contributed to the lack of significant effect across studies and pooled analyses (46). Additionally, interindividual differences in the absorption and elimination of glucosamine may cause variable clinical outcomes in OA according to a study of healthy adults (48).
Clinical trials on whether glucosamine can improve temporomandibular joint (TMJ) symptoms are limited and generally provide only low evidence of this effect (1) (41), although one study of oral glucosamine adjunctive to hyaluronic acid injection suggests long-term benefit (42). Glucosamine combined with conventional treatment was also found effective in improving pain and function in patients with hand osteoarthritis (49).
In addition to arthritic conditions, glucosamine has been assessed for its potential role against depression. Although preclinical studies found that it exerts anti-depressive effects, a clinical investigation failed to find any benefit (50).
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 (17) (18) (19).
There are case reports of liver injury/toxicity related to glucosamine consumption (20) (21). Patients on antiplatelet or anticoagulant therapies should be monitored for interactions or increased INR levels (22) (23). Patients with poorly controlled diabetes or glucose intolerance should be monitored as glucosamine could worsen insulin resistance (24) (25).
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 (26). Glucosamine can protect cartilage from metabolic impairment by NSAIDs, corticosteroids, and by exerting anti-inflammatory effects (27). It may promote cartilage repair by inducing tissue TGFβ1 and CTGF expression that regulates chondrocyte proliferation (28). Long-term reductions in TMJ symptoms with adjunctive oral glucosamine may be due to TGF-beta stimulation and IL-1beta / IL-6 suppression (42). Reduced systemic inflammation and cytokine activity found in a small randomized crossover study may explain potential reductions in mortality or cancer risk (30).
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 (29).
- 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 (20) (21).
- 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 (22) (23) (24) (25) (29).
- Individuals should consult their doctor if allergic to shellfish (32).
Glucosamine tends to be safe and well tolerated (43), but caution should be exercised in certain populations (see Warnings and Interactions).
Chronic tubulointerstitial nephropathy: In a 67-year-old patient who took glucosamine daily for 3 years for OA knee pain (44).
Increased intraocular pressure: In a randomized double-blind trial, glucosamine sulfate supplementation significantly increased intraocular pressure in older patients with OA (29). The implication of this finding needs further evaluation.
Liver injury/hepatotoxicity and elevated aminotransferase values: In patients with liver disease (20) (21).
Reduced glucose tolerance: From infusion and oral forms of glucosamine (34).
Analysis of 366 adverse drug reactions to glucosamine and chondroitin preparations showed 263 cases had hypersensitivity reactions. These included mild (eg, pruritus, urticaria and lip oedema); moderate (such as dyspnoea, nausea and abdominal pain); and severe (including amnesia, gait disturbance, somnolence and hypotension) (51).