Ozonated Olive Oil for Wound Healing and Recovery

Ozone (O₃) is a highly reactive, unstable gas molecule formed from oxygen (O₂) through an electrical discharge. Due to its short half-life in gas form, it cannot be stored. To enable therapeutic application, ozone is bubbled through a base oil, primarily olive oil but other oils can be used, to create ozonated oils. This process leads to the formation of stable ozone derivatives, including ozonides, peroxides, and aldehydes, which are responsible for the therapeutic effects of Ozonated oil. Olive oil, rich in unsaturated fatty acids, acts as a carrier for these active ozone species, prolonging their shelflife and allowing for topical application.

Ozonated oil has created a lot of interest in wound care due to its antimicrobial, anti-inflammatory, regenerative and antioxidant properties, ofering a non-antibiotic approach to managing complex chronic wounds.

Mechanism of Action

OOO exhibits a broad-spectrum antimicrobial activity against bacteria (including antibiotic-resistant strains suchas MRSA and Pseudomonas aeruginosa), fungi, and viruses. The ozonides and peroxides generated during ozonation disrupt the cytoplasmic membranes, cell walls, and lipid molecles of microbial pathogens, leading to their deactivation. This direct batericidal effect is crucial in combating wound infections, which often stop the healing process.

Ozonated oil influences the inflammatory phase of wound healing with its anti-inflammatory properties. While ozone itself is a potent oxidizing agent, when applied in controlled therapeutic concentrations via ozonated oil, it also activates a controlled oxdative stress. This controlled stress triggers the activation of endogenous antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, which help restore the oxidant / antioxidant balnce in the wound. This modulation can reduce inflammation, which is a common obstacle to chronic wound healing.

• Regeneration. Ozonated oil stimulates the formation of new blood vessels (angiogenesis) and neovascularization by increasing the expresion of vascular endothelial growth factors (VEGF) and cyclin D1. BEtter blood supply to the wound site is vital for delivering oxygen, nutrients, and immune cellswhich are necessary for tissue repair and regeneration. This improves oxygenation and also support cellular metabolism within the healing tissue.
• Cell Growth and Tissue Repair. Ozonated oil promotes the proliferation of fibroblasts and keratinocytes, essential cells for wound closure and tissue regeneration. It increases significant collagen content and also tensile strength in the healing tissue, resulting in beter scar formation. This is key for strengthening the repaired tissue and preventing repetition. Ozonated oil also aids in the tisue debridement effect, helping to remove necrotic tissue and helping the forming of healthy granulation in the tisue.
• Optimized Oxygen Use Peroxides contribute to improved oxygen release and its availability by modulating the antioxidant molecules in red blood cells. This better  oxygenation at the cellular level is critical for overcoming hypoxia often present in chronic wounds, which impediments healing.
• Immune Sytem. The bactericidal properties of Ozonated oil indirectly activate components of both cellular and humoral immunity, including the activation of phagocytosis and impvoring the synthesis of cytokines (e.g. interferons) and the interleukin tumor necrotic factor. This helps bolster the local immune rsponse against pathogens.

Applications in Wound Care

Ozonated oil finds numerous applications in wound care due to its broad-spectrum therapeutic benefits. Chronic wounds is a primary area of application. They include:

• Diabetic Foot Ulcers (DFUs). Studies indicate Ozonated oil´s efficacy in improving wound grade, drainage, and overall healing in DFUs by strongly combating infection, reducing inflammation, and stimulating tissue regeneration.
• Pressure Ulcers (Bedsores). Ozonated oil´s ability to encourage granultion tissue growth and improve local circulation makes it very effective for managing pressure ulcers.
• Venous Stasis Ulcers (VSUss). Ozonated oil´s can also help address the chronic inflamation and poor circulation associated with VSUs.

Other areas of application include:

• Acute Wounds. Ozonated oil can speed up the healing of acute cutaneous wunds, including post surgical wounds, by helpingfaster wound closures, collagen synthesis, and fibroblast proliferation.
• Infected Wounds. Ozonated oil´s potent antimicrobial activity makes it a valuable complementin managing various infected wounds, reducing the microbial load and preventing furtherwound complications.
• Burns. Ozonated oil can aid in healing burns by reducing pain, preventing post-lesion hyperpigmentation, and advancingtissue repair.
• Aphthous Ulcers (Mouth Sores). Topical application has shown to reduce pain and accelerate healing of oral ulcers.
• Post-Surgical Wounds. Ozonated oil can be used to promote quicker healing, reduce pain, and control infection after surgical procedures.
• Dermatological Conditions. Aside from wounds, Ozonated oil is used for numerous skin conditions characterized by irritation, redness, dryness, and infections, such as acne, seborrhea, dermatitis, eczema, pscoriosis, rosacea, scars, stretech marks, and cold sores / herpes.

Scientific Literature

A lrage and expanding body of scientific literature supports the use of Ozonated oil in wound healing.

In vitro and In vivo studies have demonstrated the antimicrobial, anti-inflammatory, pro-angiogenic, and tissue-regenerative effects of Ozonated oil in laboratory settings and animal models. For example, studies on guinea pigs have shown that topical application of Ozonated oil accelerates acute cutaneous wound repair together with increased expression of PDGF, TGF-β, and VEGF, and promotes collagen synthesis and fibroblast proliferation.

Systematic reviewsof existing literature highlight the effectivness of ozonated olive extract in improving wound healing, citing benefits such as reduced microbial infction, debridement, modulation of inflamation, angiogenesis stimulation, and enhanced oxygen metabolism.

While more large-scale randomized controlled trials (RCTs) are recommended, existing clinical studies show excelent results:

• Diabetic Foot Ulcers. Some trials have found ozonated olive ointment to be more effective than conventional solutions across various grades of DFUs. A recent randomized controlled trial involving nurse-led intervntions with Ozonated oil demonstrate muchbetter outcomes in ulcer healing, including complete and partial healing, improved wound grade, and reduced drainage compared to a control group.
• Pediatric Hypospadias Repair. A prospective randomized clinical trial showd that an ozonide-based product in a spray formulation promoted faster wound healing compared to convntional hyaluronic acid cream, with lower rates of foreskin dehiscence and re-operation.
• Dental Post-Extraction Wound Healing. Studies have shownthat topical ozone gel significantly improves postoperative pain, mouth opening range, and promotes faster wound healing after tooth extractions.
• Recurrent Aphthous Stomatitis. Comparative studies have indicated that Ozonated oil significantly decreases pain and erythema and improves ulcerhealing in canker sores / salt blister.

References

Abasi Niasar, A., Abdi, F., Jandaghian-Bidgoli, M., Akbarzadeh Amirdehi, M., Bahrami, T., Khanchemehr, Y., & Yaghobi, M. (2025). The Effect of Nurse-Led Intervention on the Healing of Diabetic Foot Ulcers with Ozonated Olive Oil: A Randomized Controlled Trial. Journal of Nursing and Midwifery Sciences, 12(1). [Retrieved from ResearchGate or Brieflands if available, as per search results indicated a recent publication].

El-Sayed, E. A. (2021). Ozonated oil in wound healing: what has already been proven? Journal of Advances in Medicine and Medical Research, 33(23), 57–63.

El-Said, M., El-Ghobashy, Y. A., & Mohamed, A. (2023). Changes in the Quality Parameters and Antimicrobial Activity of Ozonated Virgin and Pomace Olive Oils Under Different Storage Conditions. Molecules, 28(6), 999.

Feng, C., Geng, J., Wang, S., & Zhang, H. (2016). Ozone oil promotes wound healing by increasing the migration of fibroblasts via PI3K/Akt/mTOR signaling pathway. Molecular Medicine Reports, 14(5), 4417–4424.

Lana, A., El-Saadany, S. A., El-Hossary, H., & El-Hadidy, S. (2024). Comparative evaluation of efficacy of topical ozonated olive oil and topical chlorohexidine gluconate in management of recurrent aphthous stomatitis. Journal of Dentistry and Oral Sciences Research, 10(1), 10–15. [This reference is based on the search result and implies a recent publication, exact pagination might vary based on final journal release].

Niasar, M. A., Fayazi, S., Jahani, S., Yazdanpanah, L., & Haghighizadeh, M. H. (2015). The effect of topical olive oil on the healing of foot ulcer in patients with type 2 diabetes: A double-blind randomized clinical trial study in Iran. Journal of Clinical and Diagnostic Research, 9(4), IC01–IC04.

Saglam, A. B., & Köse, Ö. (2023). Comparative Efficacy of Red Beetroot Extract and Ozonated Olive Oil on Wound Healing in Rats. Journal of College of Physicians and Surgeons Pakistan, 33(12), 1385–1388.

Scandiffio, R., Rossi, C., Cifone, M. G., & Condò, S. G. (2018). Evaluation of the antibacterial activity of a new ozonized olive oil against oral and periodontal pathogens. Molecular Medicine Reports, 17(1), 1279–1284.

Valacchi, G., Bocci, V., & Travagli, V. (2010). Ozone and Ozonated Oils in Skin Diseases: A Review. Clinical Dermatology, 28(4), 438–446.

Vega, G., & Chang, R. (2019). Ozonated Oils as Antimicrobial Systems in Topical Applications. Their Characterization, Current Applications, and Advances in Improved Delivery Techniques. Antibiotics, 9(1), 22.

Vieira, F. H., Borges, V. P., & da Silva, T. S. A. (2025). Technical Considerations of Ozonated Oils in Medical Applications: A Narrative Review. Biomedicines, 13(5), 785.

Özdemir, A., & Çelebi, M. (2012). Cytological assessment of healing palatal donor site wounds and grafted gingival wounds after application of ozonated oil: an eighteen-month randomized controlled clinical trial. Journal of Periodontology, 83(8), 1018–1026.