Glucosamine for knee osteoarthritis: an umbrella review

Knee osteoarthritis (OA) is a common cause of pain and disability without a cure. Glucosamine is widely used as a symptomatic treatment owing to its safety, yet its clinical efficacy remains uncertain amid mixed trial results and conflicting guidelines. This umbrella review synthesized evidence from published systematic reviews and meta-analyses on the effectiveness and safety of glucosamine in knee OA.

We searched MEDLINE (via PubMed), Embase, Web of Science, and the Cochrane Library up to November 2025. Eligible studies were systematic reviews or meta-analyses of randomized trials in adults with knee OA comparing glucosamine (any formulation) with placebo or other non-surgical comparators and reporting pain, physical function, or joint structure. Two reviewers independently screened, extracted data, and assessed quality (AMSTAR-2). Key outcomes were pain (visual analog scale [VAS] and WOMAC [Western Ontario and McMaster Universities Osteoarthritis Index]), functional measures, joint space narrowing (JSN), and adverse events. Overlap among shared primary trials was quantified using the corrected covered area, and the resulting dependence was addressed using robust variance estimation to pool standardized mean differences (SMDs), with p < 0.05 considered significant. Effect sizes were interpreted against minimal clinically important difference (MCID) thresholds.

Nineteen reviews were included (most low or critically low quality). Glucosamine produced a small but statistically significant reduction in VAS pain (SMD - 0.36, p = 0.02), whereas WOMAC pain showed no significant difference. Functional outcomes (WOMAC total and function) showed no significant improvement. Glucosamine was associated with significant slowing of JSN progression (SMD - 0.32, p = 0.01), though this signal derived mainly from long-duration sulfate trials. The magnitude of the significant effects was at or below accepted MCID thresholds. Adverse event rates did not differ from placebo.

Glucosamine demonstrated at most minimal-to-modest efficacy for knee OA, yielding a small pain reduction and possible slowing of radiographic progression but no clear functional benefit, with effects at or below the threshold of clinical importance. Given the low quality of evidence, extensive overlap among reviews, and the predominantly out-of-pocket nature of glucosamine use, these findings should be interpreted with caution and weighed against cost in shared decision-making.

https://www.crd.york.ac.uk/prospero/, identifier (CRD420251207513).