Ozonotherapy: Applications and Methods
Ozone therapy is primarily used as an environmental disinfectant for viral inactivation on surfaces, in air, and in water, but has limited and controversial applications in direct medical treatment. The evidence strongly supports its use for environmental disinfection rather than as a primary medical intervention for patient care.
Primary Applications of Ozone Therapy
Environmental Disinfection (Strongest Evidence)
Gaseous ozone is most effectively used for disinfecting surfaces, air, and equipment in healthcare and public settings, particularly for viral inactivation including SARS-CoV-2 1.
Recommended concentrations and exposure times:
- Small chambers/items: 10-50 mg/m³ for 10-50 minutes 1
- Large rooms: 30-50 mg/m³ for 20-30 minutes 1
- Extended low-dose disinfection: 5-10 mg/m³ for 4 hours when time permits 1
- Occupied spaces: <0.1 mg/m³ to prevent SARS-CoV-2 spread while people are present 1
Critical safety parameters:
- Short-Term Exposure Limit (STEL): 0.30 ppm (0.60 mg/m³) 1
- Transitional Limit (TWA): 0.10 ppm (0.20 mg/m³) 1
- Rooms must be unoccupied during high-concentration disinfection due to respiratory toxicity 1
Application Methods by Medium
Water disinfection:
- Ozonized water at 5-20 mg/L achieves viral inactivation within 1 minute 1
- Applied as sprays or compresses, particularly in dental medicine 2
- Effective against influenza H1N1 and H5N1 with 99.99% inactivation at 0.5-1 mg/L for 10 minutes 1
Surface disinfection:
- Personal protective equipment (PPE) including N95 respirators, face masks, and disposable gowns can be treated for safe reuse 1
- Requires relative humidity ≥50% for optimal effectiveness 1
- Materials maintain protective function after treatment, though elastic straps may be affected 1
Airborne disinfection:
- Achieves 3-log viral inactivation in aerosols at lower CT values compared to surfaces 1
- Mobile commercial ozone generators can disinfect offices, hotel rooms, and enclosed spaces 1
Medical Applications (Limited Evidence)
Direct medical ozone therapy is administered through several routes, though evidence for clinical efficacy is substantially weaker than for environmental disinfection 3, 2:
- Parenteral oxygen/ozone gas mixture (most studied intervention with 192 associations across outcomes) 3
- Ozonated water (parenteral or topical application) 3, 2
- Transcutaneous ozone gas baths at sub-atmospheric pressure for external wounds 2
- Autohemotherapy (blood ozonation and reinfusion) 2, 4
- Topical ozonated oil 3
- Gas introduction into body cavities 4
Claimed therapeutic targets include:
- Infected wounds and wound healing 3, 2
- Circulatory disorders 2
- Age-related macular degeneration 2, 5, 6
- Chronic inflammatory conditions 3, 6
- Pain control 3
Mechanisms of Action
Ozone inactivates pathogens through oxidative damage:
- Breakdown of viral proteins and lipid membranes 1
- Removal of Zn²⁺ from protein finger domains with disulfide bond formation 1
- Inactivation of bacteria, viruses, fungi, yeast, and protozoa 2
In medical applications, proposed mechanisms include:
- Stimulation of oxygen metabolism 2
- Activation of immune system 2
- Enhancement of rheological properties of blood 4
Enhanced Disinfection Strategies
Synergistic combinations improve efficacy while reducing required ozone concentrations 1:
- Ozone + hydrogen peroxide: Generates hydroxyl radicals (H₂O₂ + 2O₃ → 2·OH + 3O₂) 1
- Ozone + UV light: Produces additional reactive oxygen species 1
- Ozone + ultrasound: Enhances ozone decomposition and radical generation 1
These combinations achieve superior inactivation (e.g., 5.2 log reduction) compared to ozone alone (<0.6 log reduction) 1.
Critical Safety Considerations
Major hazards and precautions:
- Respiratory toxicity: Ozone is highly toxic to the respiratory system and requires strict concentration control 1, 2, 6
- Post-treatment ventilation: Use catalytic decomposition (MnO₂/Al₂O₃, MnO₂/AC) to reduce residual ozone to <10 ppb, or open windows for natural ventilation 1
- Material corrosion: High concentrations can damage building materials and equipment 1
- Unoccupied spaces required: High-dose disinfection must occur without human presence 1
For high-risk areas like hospitals:
- Multiple daily disinfection cycles recommended 1
- Enhanced cleaning of high-touch surfaces (keyboards, phones, scanners) 1
- Improved ventilation systems to reduce airborne transmission 1
Evidence Quality and Limitations
The evidence base differs substantially by application:
- Environmental disinfection has robust support from controlled studies demonstrating consistent viral inactivation 1
- Direct medical therapy evidence is weaker, with systematic reviews noting minimal serious adverse effects but limited high-quality efficacy data 3
- Ozone was not initially recognized as a virucidal agent by major regulatory bodies (Spanish Health Ministry, US EPA) due to inconsistent parameters and mechanisms 1
Key factors affecting efficacy: