Ozonotherapy: Clinical Applications and Administration
Do not use ozone therapy for treating medical conditions in clinical practice, as current high-quality guidelines strongly recommend against its use due to insufficient evidence of benefit and lack of established safety profiles. 1
Guideline Recommendations
The most recent and authoritative clinical guidelines explicitly advise against ozone therapy:
The 2024 International Working Group on the Diabetic Foot (IWGDF) guidelines strongly recommend against using ozone and other gases (including cold atmospheric plasma, nitric oxide, and CO2) for wound healing in diabetic foot ulcers, citing very low certainty of evidence, trivial desirable effects, and high risk of bias in available studies. 1
The 2025 EULAR guidelines for systemic sclerosis identified only one small RCT on oxygen-ozone therapy for digital ulcers, which showed a 20-day follow-up period—far too short to establish meaningful clinical benefit. The guidelines noted that blinded and placebo-controlled studies are needed before any recommendation can be made. 1
Proposed Mechanisms and Applications
Despite guideline recommendations against clinical use, ozone therapy has been studied for various conditions, though the evidence remains inadequate:
Theoretical Mechanisms
- Oxidative stress induction: Ozone acts as a strong oxidizing agent that theoretically stimulates oxygen metabolism and immune system activation. 2, 3
- Antimicrobial effects: Proposed inactivation of bacteria, viruses, fungi, and protozoa through peroxidation of cellular structures. 2
Conditions Studied (Without Proven Efficacy)
- Chronic wounds (diabetic foot ulcers, venous leg ulcers, digital ulcers) 4, 5, 6
- Dermatological disorders (onychomycosis, atopic dermatitis, cutaneous leishmaniasis) 6
- Infectious diseases 2, 5
- Pain and inflammatory conditions 5
Administration Methods
When ozone has been studied experimentally, various delivery methods have been reported:
- Topical application: Ozonated water sprays, ozonated oils, or transcutaneous gas baths at sub-atmospheric pressure in closed systems 2, 3
- Parenteral routes: Oxygen/ozone gas mixtures or ozonated water administered systemically 5
- Local wound care: Direct application to wound beds 1, 4
Critical Evidence Gaps and Safety Concerns
Why Guidelines Recommend Against Use
- High risk of bias: No studies on ozone therapy for medical conditions have been assessed as low risk of bias 1
- Inconsistent results: Three studies addressing cutaneous leishmaniasis, skin ulcers, and burns showed lack of effectiveness 6
- Inadequate follow-up: Most trials have extremely short follow-up periods (as brief as 20 days), insufficient to assess meaningful clinical outcomes 1
- Respiratory toxicity: Ozone is toxic to the respiratory system, requiring extremely controlled conditions 3
- Lack of standardization: No established dosing protocols, concentration ranges, or treatment duration guidelines exist 2
Limited Quality Evidence
A 2018 systematic review of ozone therapy for chronic wounds found no conclusive evidence of superiority compared to standard treatments, despite some improvement in wound closure rates. 4
Environmental Disinfection Context
Important distinction: The evidence showing ozone effectiveness relates to environmental disinfection (surface and air disinfection for SARS-CoV-2, influenza, and other viruses), not medical treatment of human diseases. 1
- Gaseous ozone can inactivate viruses on surfaces and in aerosols at specific concentrations (0.1-0.4 mg/L·min for aerosols; 1-4 mg/L·min for surfaces) 1
- This application is for environmental control only, not therapeutic use in patients 1
Clinical Bottom Line
Ozone therapy should not be used in clinical practice for treating medical conditions. The highest quality, most recent guidelines from major international societies explicitly recommend against its use due to insufficient evidence, high risk of bias in existing studies, and unclear safety profiles. 1 Standard evidence-based treatments should be employed instead for all conditions where ozone has been proposed.