Hyaluronic acid

Do hyaluronic acid injections help knee osteoarthritis?

Updated 9 Nov 2026

Short answer

Only a little. A 2022 meta-analysis of large placebo-controlled trials found that knee injections lowered pain by 2 mm on a 100 mm scale more than placebo, which is less than patients notice. They also raised the risk of serious adverse events.[1] NICE in the UK advises doctors not to offer them.[2]

What these injections are

Viscosupplementation means injecting hyaluronic acid into the knee joint. It is widely used for knee osteoarthritis.[3] In one large trial, people got 3 weekly injections of 20 mg.[4]

What the reviews found

A 2022 meta-analysis in the BMJ included 169 trials with 21,163 people:[1]

  • It found signs of small-study effects and publication bias: the results depended on trial size and on which trials were published.[1]
  • In 24 large placebo-controlled trials with 8,997 people, injections lowered pain by 2.0 mm on a 100 mm scale more than placebo. This is below the smallest difference that patients notice.[1]
  • Since 2009, the evidence has shown that injections and placebo work about the same. Results for joint function were similar.[1]
  • In 15 large trials with 6,462 people, injections raised the risk of serious adverse events (relative risk 1.49).[1]

The authors concluded that the findings do not support broad use of these injections for knee osteoarthritis.[1]

A 2012 meta-analysis of 89 trials with 12,667 adults found the same pattern:[3]

  • Together, 71 trials with 9,617 patients showed a moderate effect on pain.[3]
  • 18 large trials with blinded assessment showed an effect too small to matter.[3]
  • 5 unpublished trials showed almost no effect.[3]
  • Flare-ups of knee pain after injection were more common, but the difference was not statistically significant (relative risk 1.51).[3]
  • Injections raised the risk of serious adverse events (relative risk 1.41).[3]

The authors judged the quality of most trials to be low, and many trials did not report safety data.[3]

Why some single trials look positive

In the FLEXX trial, 588 people got 3 injections of hyaluronic acid or of salt water. After 26 weeks, pain on walking fell by 25.7 mm with hyaluronic acid and by 18.5 mm with salt water. The authors report a difference of 6.6 mm between the groups.[4] Reactions at the injection site were rare: 2 people (1%) had one after hyaluronic acid and 1 person (less than 1%) after salt water.[4] Salt water injections also lowered pain a lot.[4] The meta-analyses measure the difference between the groups, and in large trials it was small.[1]

What guidelines say

NICE, the UK body that writes clinical guidelines, says in its 2022 guideline on osteoarthritis: "Do not offer intra-articular hyaluronan injections to manage osteoarthritis."[2]

Who should be careful

Injections are given by a doctor. Ask about the risk of serious adverse events before a course of injections.[1] Results of injection trials do not apply to tablets. In mice, gut bacteria broke down swallowed hyaluronic acid, and only about 0.2% was absorbed.[5]

Sources (5)

  1. Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis. Pereira TV, Jüni P, Saadat P, Xing D, Yao L, Bobos P, et al. BMJ, 2022. PMID 36333100
  2. Osteoarthritis in over 16s: diagnosis and management. National Institute for Health and Care Excellence, 2022. www.nice.org.uk
  3. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S Ann Intern Med, 2012. PMID 22868835
  4. A double-blind, randomized, saline-controlled study of the efficacy and safety of EUFLEXXA for treatment of painful osteoarthritis of the knee, with an open-label safety extension (the FLEXX trial). Altman RD, Rosen JE, Bloch DA, Hatoum HT, Korner P Semin Arthritis Rheum, 2009. PMID 19539353
  5. Molecular weight and gut microbiota determine the bioavailability of orally administered hyaluronic acid. Šimek M, Turková K, Schwarzer M, Nešporová K, Kubala L, Hermannová M, et al. Carbohydr Polym, 2023. PMID 37182970

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For education; not medical advice. Talk to a doctor before you start, stop or change a supplement.