- Glucosamine sulphate
- Glucosamine hydrochloride
For Patients & Caregivers
Bottom Line: Conclusive evidence is lacking to support effectiveness of glucosamine against arthritis.
Cartilage is composed of collagen, elastin, and a matrix of long sugar-protein molecules called proteoglycans and glycosaminoglycans (GAGs). GAGs are extremely important for the ability of cartilage to act as a shock absorber, because they are highly negatively charged and absorb water so that cartilage is gel-like and resilient. Osteoarthritis is characterized by a progressive degeneration of cartilage GAGs. Glucosamine facilitates the synthesis of GAGs, and therefore replenishing the availability of these molecules would slow the degeneration of cartilage. However, clinical trials yielded mixed results. Glucosamine can also protect cartilage from damage by NSAIDs, corticosteroids and by reducing inflammation.
- To reduce inflammation
Glucosamine may reduce inflammation by a mechanism that is different from the way typical non-steroidal anti-inflammatory drugs (NSAIDs - e.g., aspirin, ibuprofen) work. Although glucosamine helps improve symptoms in osteoarthritis, no scientific evidence supports the use of glucosamine frr any other inflammatory conditions.
- To prevent progression of and treat osteoarthritis
Several clinical trials on using glucosamine alone and in combination with chondroitin sulfate yielded mixed results.
- To treat temporomandibular joint disorder (TMJ)
Two clinical trials support the use of glucosamine in combination with chondroitin sulfate to treat TMJ.
The results of 15 randomized, controlled trials that used glucosamine or chondroitin sulfate for treating osteoarthritis were analyzed. Overall, these clinical trials found that glucosamine and chondroitin sulfate are moderately effective when used separately to treat osteoarthritis - glucosamine moreso. However, these effects might be somewhat overestimated, because this meta-analysis also found that publication bias existed. Publication bias occurs when only clinical trials that showed beneficial effects of a therapy are published in journals, while clinical trials that showed no effects are not published and therefore not included in meta-analyses.
The ability of glucosamine to prevent progression of osteoarthritis of the knee was studied in a randomized, controlled trial. Every day for three years, 212 patients took either 1500 mg of glucosamine sulfate or a placebo pill. Physicians evaluated patients’ progress by 1) taking an x-ray of the knee and measuring the width of the joint space between the tibia and femur, and 2) asking the patients about their symptoms. At the end of the study, patients taking glucosamine had no joint-space narrowing, whereas patients taking placebo had an average joint-space loss of 0.31 mm after three years. Patients taking glucosamine also had a significant reduction in symptoms in comparison. This large, well-designed study supports the efficacy of glucosamine in slowing the progression of knee osteoarthritis.
A similar study was conducted in 202 patients with mild to moderate osteoarthritis of the knee. The patients were randomly assigned to take either 1500 mg of glucosamine sulfate or a placebo pill daily for three years. Again, patients taking glucosamine had no joint-space narrowing, while patients taking placebo had a joint-space narrowing of 0.19 mm. In addition, fewer patients in taking glucosamine had ’severe’ narrowing (>0.5 mm), and on average, they reported a greater reduction in symptoms. This large, well-designed study adds further support to the idea that glucosamine can slow the progression of knee osteoarthritis.
- People with diabetes should consult with their doctor before beginning to use glucosamine, because it has been reported to affect blood insulin levels and glucose metabolism in the body when used intravenously. Although this effect has not yet been seen when glucosamine is taken by mouth, diabetics using glucosamine should check their blood sugar level more frequently.
- This product is regulated by the F.D.A. as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. The product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
- Adverse reactions are rare and glucosamine tends to be safe and well tolerated.
- Stomach upset
- Leg pain
- Edema (swelling)
- Allergic reactions
- Glucosamine-chondroitin combination may potentiate the effects of warfarin.
- Glucosamine use has been associated with increased INR returning to normal levels when glucosamine was discontinued.
- Concomitant use of glucosamine and warfarin resulted in increased INR.
- Use of glucosamine and celadrin may inhibit platelet aggregation.
- A study in rats suggests that oral consumption of potent glucosamine preparations may cause sclerotic side effects.
- Glucosamine has not been found effective in relieving back pain.
- Glucosamine may have a limited effect in older patients who have more severe arthritis or have had arthritis for longer periods of time.
- Glucosamine may take longer to act than NSAIDs, but once it does, its effects last longer after treatment is stopped.
For Healthcare Professionals
Glucosamine is an endogenous aminomonosaccharide synthesized from glucose. Found in mucopolysaccharides, mucoproteins and chitin (a cellulose-like biopolymer that is a major component of the exoskeleton of various marine invertebrates), it is used in the biosynthesis of proteoglycans and glycosaminoglycans. Glucosamine is often paired with chondroitin sulfate in the treatment of articular diseases.
Two small studies involving glucosamine and chondroitin showed improvement in reducing symptoms of temporo-mandibular joint (TMJ) disorder (2) and degenerative joint disease (DJD). A meta-analysis suggests that it is effective against osteoarthritis of the knee (1). However, data from other studies indicate no such benefits of glucosamine, chondroiting or the combination in preventing progression of knee or hip osteoarthritis (13)(18)(17)(19)(23). Data on efficacy of chondroitin alone are also conflicting (1)(16)(23).
No efficacy was seen with glucosamine in relieving back pain (3)(22), degenerative lumbar osteoarthritis (22), or in improving glucose metabolism in patients with type 2 diabetes mellitus (15). Studies have indicated that the effects of glucosamine may be limited in older patients who have more severe arthritis (4) or have had arthritis for longer periods of time (5).
A progressive degeneration of cartilage glycosaminoglycans is evident in osteoarthritis. Glucosamine is the first step in glycosaminoglycan biosynthesis and has been shown to increase proteoglycan amounts in vitro, by affecting the synthesis of monomeric proteoglycans capable of assembling into high molecular weight aggregates (7). Glucosamine can protect cartilage from metabolic impairment by NSAIDs, corticosteroids and by exerting anti-inflammatory effects (8).
Glucosamine may be administered via intravenous, intramuscular or oral routes. Intravenous and intramuscular administration appears in the plasma and is rapidly eliminated. t1/2 is 0.28h. 1-2 hours after administration, glucosamine or its metabolites have been entirely incorporated into plasma proteins. Oral administration of glucosamine sulfate yields 90% absorption. Incorporation is similar to parenteral administration although the plasma level is five times smaller due to a first pass effect in the liver. After administration or ingestion, glucosamine sulfate is split into D-glucosamine and a sulfate ion. D-glucosamine is a small, neutral molecule that has a special tropism for cartilaginous bone tissue.
- Reported adverse reactions include gastrointestinal complaints, headache, leg pain, edema, itching (8) and possible allergic reactions (2).
- Glucosamine-chondroitin combination may potentiate the effects of warfarin (20).
- Glucosamine use has been associated with increased INR returning to normal levels when glucosamine was discontinued (20).
- Concomitant use of glucosamine and warfarin resulted in increased INR (20).
- Use of glucosamine and celadrin may inhibit platelet aggregation through aspirin-like effects and by inhibiting the ADP receptor P2Y1 but not P2Y12 (21).
- A study in rats suggests that oral consumption of potent glucosamine preparations may cause sclerotic side effects (24).
A study in 10 people found that an infusion of glucosamine sulfate reduced glucose tolerance. This observation and recent in vitro evidence suggest that glucosamine can increase insulin resistance, resulting in the need for larger doses of insulin or oral hypoglycemic agents in diabetic patients (14).
Sawitzke AD, Shi H, Finco MF, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: A report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum 2008 Sep 29;58(10):3183-3191.
This is a multicenter, double-blind, placebo-controlled study and a part of the Glucosamine/Chondroitin Arthritis intervention Trial (GAIT) involving 572 patients with knee osteoarthritis. Patients were randomized to receive Glucosamine (500 mg, 3 times daily); Chondroitin Sulfate (CS) (400 mg, 3 times daily); combination of Glucosamine and CS; Celecoxib (200 mg daily); or placebo over two years. The primary outcome measure was mean change in loss of joint space width (JSW) from the baseline.
Researchers reported no clinically significant differences in loss of JSW between any treatment and placebo groups. But patients in the Glucosamine group had the least mean loss in JSW, while those in the combination group had the greatest mean loss. This may be due to reduced absorption of Glucosamine when used along with CS.
The limitations of the study include a smaller sample size, short duration of the study and use of radiographs for JSW measurements.
McAlindon TE, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-75.
Meta-analysis of 15 RCTs of glucosamine or chondroitin lasting four or more weeks. Studies were given quality scores and showed publication bias. The aggregated effect size for glucosamine was 0.44, which corresponded to moderate effect. Restricting measurement to larger and higher-quality studies diminished the effect size. Nevertheless, some level of efficacy was supported.
Reginster YJ, et al. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet 2001;357:251-6.
An RCT of 212 patients with osteoarthritis of the knee. Patients received either oral glucosamine sulfate 1500 mg daily or placebo for three years. Minimum and mean joint-space width of the medial compartment of the tibiofemoral joints were measured after one and three years. Symptoms were scored by WOMAC. Patients in the treatment arm experienced no joint-space narrowing, whereas patients in the control arm experienced mean joint-space loss of 0.31 mm after three years. In an intention-to-treat analysis, patients showed a statistically significant reduction in WOMAC score after three years. Adverse effects were similar to placebo in this study. This large, well-designed study supports the efficacy of glucosamine in retarding the progression of knee osteoarthritis.