Is glucosamine (glucosamine hydrochloride or glucosamine sulfate) beneficial for patients with osteoarthritis?

Glucosamine for Osteoarthritis: Not Recommended

Glucosamine is strongly recommended against in patients with knee, hip, and/or hand osteoarthritis as it does not provide significant benefits over placebo for improving pain or function. 1

Evidence Against Glucosamine Use

The 2019 American College of Rheumatology/Arthritis Foundation guidelines provide a strong recommendation against the use of glucosamine for osteoarthritis management, representing a change from prior conditional recommendations 1. This position is supported by:

• Data with the lowest risk of bias fail to show any important benefits over placebo
• Discrepancies between industry-sponsored and publicly funded studies raise serious concerns about publication bias
• Lack of clear biological understanding of how efficacy would vary with different salt formulations
• Large placebo effects observed in clinical trials

The 2008 NICE guidelines similarly do not recommend the use of glucosamine and chondroitin products for osteoarthritis management 1.

Formulation Considerations

Some important distinctions exist between glucosamine preparations:

• Pharmaceutical-grade preparations (typically glucosamine sulfate) have been studied in multiple trials
• Over-the-counter supplements may have reliability issues concerning their content
• Discrepancies between results from patent-protected formulations distributed as drugs versus supplements purchased from global suppliers 2

Safety Profile

While glucosamine is not recommended for efficacy reasons, its safety profile is generally favorable:

• Low potential toxicity
• Some patients exposed to glucosamine may show elevations in serum glucose levels, requiring monitoring 1
• Side effect profile similar to placebo in most studies 3

Recommended Alternatives for OA Management

Instead of glucosamine, the following evidence-based approaches are recommended:

1. Core treatments (should be offered to all patients with symptomatic OA):

   • Education about the condition
   • Exercise therapy (local muscle strengthening and general aerobic fitness)
   • Weight loss interventions if overweight or obese 1

2. First-line pharmacological options:

   • Paracetamol (acetaminophen) for pain relief
   • Topical NSAIDs (particularly for knee and hand OA) 1

3. Second-line options:

   • Oral NSAIDs or COX-2 inhibitors at lowest effective dose for shortest possible period
   • Opioid analgesics when other options insufficient
   • Intra-articular corticosteroid injections for moderate to severe pain 1

Special Considerations

Despite strong recommendations against glucosamine, clinicians should be aware that:

• Many patients perceive glucosamine to be efficacious
• Patients often believe different formulations have different degrees of efficacy
• Patients may seek advice on specific brands and manufacturers 1

When patients insist on using glucosamine despite the evidence, monitor for potential glucose level elevations and explain the limited evidence for efficacy.

Chondroitin Considerations

While glucosamine is strongly recommended against for all OA types, chondroitin sulfate:

• Is strongly recommended against for knee and hip OA
• Is conditionally recommended for hand OA based on a single trial suggesting analgesic efficacy 1, 4

In summary, current high-quality evidence does not support the use of glucosamine for osteoarthritis management, and patients should be directed toward evidence-based interventions that have demonstrated efficacy in improving symptoms and quality of life.