What is Hyaluronic Acid?
Hyaluronic acid (HA) is a naturally occurring linear polysaccharide composed of repeating units of glucuronic acid and N-acetylglucosamine. It is a structural component of connective tissue, synovial fluid and skin. Injectable HA preparations are investigated in research contexts for joint and skin hydration.
This information is for research and educational purposes only. No medical advice.
Comparison
Further entries on skin and joints
Where each compound acts, as stated in the TPD lexicon. Tap a card to open its entry.
Simplified: hyaluronic acid is a sugar polymer, not a peptide. The other entries are peptides with a different approach.
How it works
Hyaluronic acid acts as a viscoelastic substance and moisture reservoir. It binds large amounts of water (up to 1000 times its molecular weight) and creates cushioning and lubrication in joints and hydration in skin.
- Highly hygroscopic (binds water)
- Viscoelastic polymer
- Anti-inflammatory properties
- Natural component of joints and skin
Where it acts
Where hyaluronic acid plays a role
Tap a point or a card. Colour = receptor, grey = effect seen in trials.
- Knee joint
As an injection in osteoarthritis, a small, clinically irrelevant effect on pain in large trials2
Observed in trials - Skin and connective tissue
Natural component, cells bind hyaluronic acid via CD446
CD44 - Eye
Vision loss when facial filler blocks a blood vessel, mostly without recovery7
Observed in trials - Liver
Breaks down hyaluronic acid from the blood, half-life in the blood 2 to 5 minutes5
Observed in trials
Known targets6
Compound CHEMBL5314376: one described target, Main receptor on the cell surface, binds hyaluronic acid.
- Gene
- CD44
- UniProt
- P16070
- ChEMBL
- CHEMBL3232692
- Action
- Main receptor on the cell surface, binds hyaluronic acid
Use
Dosing
Dosing, titration and syringe
Loading the dosing information …
- Getting started and stepping up, drawn as a staircase
- Units on the U-100 syringe for every step
- How long one vial lasts
What the research shows
Hyaluronic acid is well established in medical research. In knee osteoarthritis the trials show less pain overall. A review of 89 trials, however, concluded that the benefit is small and of little clinical relevance, with the smallest effect in large blinded trials (Rutjes 2012). In skin research, HA is examined as a moisturizer and potential collagen stimulator. Safety data are thin: many joint trials did not report safety data.
- Small effect of little clinical relevance on pain in knee osteoarthritis (Rutjes 2012)
- Skin hydration studies show positive effects
- Biocompatible, but more serious adverse events than placebo in joint trials
- Naturally occurring, low immunogenicity
Study results
What the trials measured
Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.
Effect on pain2
Effect size versus sham or no treatment, by type of trial
The larger and better blinded the trials, the smaller the effect. The authors rate it as clinically irrelevant. As a rule of thumb an effect size around 0.2 counts as small and around 0.5 as moderate.
Risk compared with control2
Relative risk, 1 means as frequent as without hyaluronic acid
Values from the abstract of the review. Many trials did not report safety data at all and trial quality was generally low. The older Cochrane review found few adverse events in the trials, but numbers too small for a firm judgement.
Half-life in the knee joint4
Labelled hyaluronic acid injected into rabbit knees, in hours
Long chains stayed only slightly longer in the joint than short ones. In the blood the half-life is 2 to 5 minutes, where hyaluronic acid is mainly broken down in the liver.
Research status
Where the research stands
ClinicalTrials.gov lists 288 entries on hyaluronic acid as a joint injection for knee osteoarthritis. Shown is a selection of large, completed phase 3 trials against placebo. As of 26 Oct 2026. 8
- Preclinical Breakdown in the knee joint (rabbits)
- Phase 1 no registered trial
- Phase 2 no registered trial
- Phase 3 5 trials, 5 completed
- Approval for specific uses
Show all 5 phase 3 trials on a timelineHide timeline
NCT00988091 · 596 participants, started Sept 2009, primary endpoint reached Oct 2010.
Registry entry ↗ · Results not yet in PubMed
NCT01372475 · 800 participants, started Mar 2011, primary endpoint reached Nov 2012.
Registry entry ↗ · Results not yet in PubMed
NCT03200288 · 692 participants, started Jun 2017, primary endpoint reached Jun 2018.
Registry entry ↗ · Results not yet in PubMed
C-SOUND · NCT03190369 · 440 participants, started Aug 2017, primary endpoint reached Jan 2019.
Registry entry ↗ · Results not yet in PubMed
JTA-KOA2 · NCT04333160 · 746 participants, started Mar 2020, primary endpoint reached Mar 2021. Tests several agents.
Registry entry ↗ · Results not yet in PubMed
Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.
On the skin
Besides injection, hyaluronic acid is a common ingredient in creams and serums applied to the skin. A review sums up that such products improved skin hydration in studies and were well tolerated (Bravo 2022). The review comes from a cosmetics company's side.
Side effects
Hyaluronic acid occurs naturally in the body, yet the injection is not free of risk:
- Local injection reactions (temporary, mild)
- Occasional local inflammation or swelling
- Allergic reactions are rare
- In joint trials serious adverse events were more frequent than with placebo (relative risk 1.41, Rutjes 2012)
- The biggest danger is injection into a blood vessel: hyaluronic acid can block it, with facial fillers up to blindness, mostly without recovery (Doyon 2024)
Storage
Hyaluronic acid vials should be stored cool and dark. The exact storage conditions depend on the formulation - typically refrigeration (2-8°C) is recommended. After opening, it should be used promptly, but unopened vials are stable for extended periods.
- Store cool (2-8°C recommended)
- Protected from light
- Do not freeze
- Keep original packaging dry
