Ozone Injections for Knee Arthritis: What a 2025 Double-Blind Trial Found

Research explained · October 11, 2026

The study in one line

In a small double-blind trial of 59 adults with knee arthritis, four weekly ozone injections into the knee cut pain far more than oxygen injections did, and a low dose worked as well as a dose twice as strong [1].

What did the researchers do?

• Design: a randomized, double-blind, three-group trial. Neither the people in it nor the doctors giving the injections knew who got what.
• Who: 59 adults aged 50 to 75 with knee osteoarthritis (moderate, Kellgren-Lawrence grade 2 or 3) and knee pain for at least six months, at a hospital in Tehran, Iran, between 2022 and 2023.
• Groups: 20 people got ozone at 40 µg/mL, 19 got ozone at 20 µg/mL, and 20 got the same volume (10 mL) of plain medical oxygen as a comparison.
• Treatment: one injection into the knee joint each week for four weeks.
• Measured: pain on a 0 to 10 scale, a standard arthritis questionnaire (WOMAC), how far the knee bends, a chair-stand-and-walk test, and how far people could walk in six minutes, up to two months after the last injection.

What did they find?

• Pain: in both ozone groups, average pain fell from about 8 out of 10 to under 3 out of 10 two months after treatment. In the oxygen group, it fell from about 7.8 to 6.
• Arthritis score: the WOMAC total (lower is better) dropped by roughly two-thirds in both ozone groups (from about 50 to 16, and 49 to 18). In the oxygen group it went from 43 to 36.
• Walking: people in the ozone groups walked about 115 to 120 meters further in six minutes than before. The oxygen group improved by about 33 meters.
• Dose: there was no meaningful difference between 20 µg/mL and 40 µg/mL on any measure.
• Who did best: people with less advanced arthritis (grade 2) responded better than those with grade 3.

The differences between the ozone groups and the oxygen group were statistically significant at one and two months [1].

How strong is this evidence?

The good: it was randomized and double-blind, the comparison group had the same injection procedure from identical-looking syringes, and the team used several standard, well-known measures. The effect sizes were large, and they line up with earlier trials of ozone injections for knee arthritis that the authors review [1].

The limits:

• It's small. About 20 people per group, at one hospital.
• It's short. Follow-up ended two months after treatment, so we don't know how long the benefit lasts. A separate one-year trial found ozone knee injections worked fastest but faded by 6 to 12 months (Raeissadat 2021), so repeat courses may be needed.
• It was registered late. The trial was listed on ClinicalTrials.gov (NCT06088706) in 2024, after it had finished. Registering in advance is the stronger practice.
• The paper isn't fully consistent. The methods describe oxygen injections for the comparison group, while the limitations section describes that group as getting standard care without injections. We've reported the methods as written.
• Other care was allowed. Everyone could keep exercising and take anti-inflammatory painkillers as needed, which wasn't tracked closely.
• Side effects weren't reported in detail in the results.
• We didn't see a funding or conflict-of-interest statement in the text we reviewed.

Overall: a well-designed but small, short study. It adds to the case for ozone injections in knee arthritis, and it needs larger, longer trials to confirm it.

What does it mean for you?

In this study, ozone injections into the knee reduced pain and improved walking in people with moderate knee arthritis, at least for two months. Results in one study don't guarantee results for any one person, and ozone therapy isn't a cure for arthritis.

• Joint injections are a clinic method. They're given by a trained practitioner and aren't done at home. See ozone injections.
• A lower dose may be enough. This trial adds to evidence that, for ozone, stronger isn't automatically better. Why the dose matters.
• Earlier may be better. People with less advanced arthritis responded more.

If you want to try ozone at home for other reasons, our free ozone therapy guide covers the home methods (joint injections aren’t one of them). Practitioners can learn IV ozone in our IV Ozone 101 training.

For the bigger picture, read ozone therapy for arthritis and ozone therapy for pain.

The study

1. Arjmanddoust Z, Nazari A, Moezy A. Efficacy of two doses of intra-articular ozone therapy for pain and functional mobility in knee osteoarthritis: a double-blind randomized trial. Advances in Rheumatology. 2025;65(1):11. Published March 6, 2025. doi:10.1186/s42358-025-00443-w · PubMed 40050950 · Free full text.