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RX & OTC Update

Glucosamine for Osteoarthritis

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Glucosmine at a Glance


  • Treating pain and stiffness

  • Improving function and walking distance

  • Most research studies used daily doses of 1,500 mg; the observed safe level for glucosamine sulfate and glucosamine hydrochloride is 2,000 mg

Side Effects

  • Diarrhea

  • Constipation

  • Nausea

  • Dyspepsia

  • Excessive gas

  • Abdominal distention and cramps

  • Potential for reaction in patient with fish allergy

Osteoarthritis (OA) is the most common form of arthritis, and it is among the top three leading causes of disability in adults.1 Because no cure exists, the goals of therapy are to control pain and improve function.3,4 These goals are primarily accomplished through nonpharmacologic measures such as exercise and weight reduction.5,6

The American College of Rheumatology views pharmacologic agents as adjuncts to nonpharmacologic measures, while the European League Against Rheumatism recommends a combination approach.3,6 Evidence-based recommendations for OA propose glucosamine sulfate as an option for symptom management.6

Mechanism of Action

Glucosamine is a natural component of the articular cartilage and synovial fluid. It causes the mucous membranes within the joints to secrete mucus to protect and lubricate.

In supplement form, glucosamine helps even the imbalance between production and destruction of the extracellular matrix, which is the cause of cartilage degradation.7

Glucosamine is available over the counter in at least three formulations: glucosamine sulfate, glucosamine hydrochloride and N-acetyl-glucosamine. The sulfate and hydrochloride forms have received the most research attention. The sulfate formulation has a more favorable result profile in clinical trials.5,8


Although glucosamine has been studied for more than 20 years, the debate about its efficacy has not been resolved. Inconsistent results may be attributed to inadequate allocation concealment, different glucosamine preparations and industry bias.9

A 2005 Cochrane Review found that updating an earlier review by adding the search term "best designed studies" produced consensus of a reduced efficacy for glucosamine. The reviewers found that by including only studies with adequate concealment, glucosamine was not significantly better than placebo in treating pain and stiffness.5 The Cochrane Review also determined that manufacturing practices may influence efficacy. Specifically, the prescription formulation of glucosamine sulfate from Rotta Pharmaceuticals significantly outperformed placebo.5 In the U.S., the distributor of Rotta's glucosamine sulfate formulation is WynnPharm.

Formulation also appears to influence trial results. The Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) was a controlled study of glucosamine hydrochloride, which the researchers determined ineffective in managing OA symptoms.2 The researchers randomly assigned 1,583 patients with knee OA to one of five treatment groups and observed them for reduction in knee pain. Glucosamine hydrochloride, either alone or in combination, was not significantly more effective than placebo. The researchers clarified this result by stating that limitations (high placebo effect and mild baseline pain levels) may have reduced the detectability of the supplementation treatment.2

The Glucosamine Unum in Die (Once a Day) Efficacy (GUIDE) trial was a controlled study that used glucosamine sulfate (Rotta preparation) and found it to be effective in the management of knee OA. In this study of 318 patients with knee OA, the researchers concluded that glucosamine sulfate was beneficial in improving pain, function and walking distance.10 In two 3-year controlled trials that also used the Rotta sulfate formulation, researchers found that glucosamine was beneficial in reducing joint structure changes and OA symptoms.11,12 A continuation study of the same patients found that the glucosamine sulfate group experienced a 57 percent decreased risk for total knee replacement surgery.13

Other factors that may contribute to inconsistent support of glucosamine use are affected joint, dosage and preparation. In a recent 2-year study of 222 patients with hip OA, the evidence did not show a significant benefit with glucosamine sulfate treatment.14 In a later subgroup analysis, researchers found that patients with concomitant knee OA experienced a greater decrease in baseline pain with glucosamine sulfate than with placebo.15 The researchers said the difference in responsiveness of knee OA and hip OA may be due to the difference in inflammatory components of each of the diseases, with knee OA having a greater inflammatory component than hip OA.15,16

Once-daily dosing is believed to play a role in the effectiveness of glucosamine. It may increase peak levels of the substance, thereby conferring a greater response.8 While most research studies used daily doses of 1,500 mg, the observed safe level for glucosamine sulfate and glucosamine hydrochloride is 2,000 mg daily.17 Earlier studies of glucosamine were mostly conducted in Europe using a dissolvable prescription-strength glucosamine.18 Liquid delivery provides greater bioavailability compared with pills.8

Side Effects

Glucosamine has received considerable scrutiny. The Cochrane Review found glucosamine's safety profile to be equal to placebo and significantly lower than NSAIDs.5 The GAIT and GUIDE studies found glucosamine hydrochloride and glucosamine sulfate, respectively, to have an acceptable safety profile with similar adverse effects as placebo.2,10 Side effects were diarrhea, constipation, nausea, dyspepsia, excessive gas, abdominal distention and cramps.11,19

Safety & Patient Education

Concerns about glucosamine use by patients with diabetes stemmed from animal studies suggesting that plasma glucose levels increased with high doses.20 Glucosamine was thought to increase hemoglobin A1c levels and decrease the effectiveness of diabetes medications. A 90-day trial of patients with type 2 diabetes and stable A1c levels found that oral glucosamine hydrochloride dosed at 1,500 mg daily did not significantly alter A1c levels.20 Another study found that a daily dose of 1,500 mg of glucosamine sulfate had no effect on blood glucose or serum insulin in healthy patients.21 In a 3-year trial, researchers found that glucosamine sulfate slightly lowered fasting plasma glucose levels.11 More-recent studies show that glucosamine does not affect insulin sensitivity or resistance.22

Allergic reaction in patients with fish allergies is another concern. Glucosamine is derived from lobster, crab and shrimp shells, not their meat. A small study in which researchers performed skin prick tests on patients with known allergies to shellfish found that participants reacted to the shellfish but not to glucosamine.23

Glucosamine is a dietary supplement and is not regulated or monitored. A study comparing advertised and actual amounts of glucosamine sulfate found that many brands contained doses below the advertised amount.24

Given the acceptable safety profile and low rate of side effects, patients should be informed about glucosamine as a potential pain management tool.22 A trial period of 2-3 months is recommended; some study participants did not notice beneficial effects for 90 days.18,22

Tatum Chisholm is a family nurse practitioner in Tacoma, WA.

References for this article can be accessed at Click on Resources, then References.

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