Written by Karen Pilkington and the CAM-Cancer Consortium.
Updated September 11, 2013

Ozone therapy

Abstract and key points

  • Ozone is an unstable, colourless gas present in the atmosphere
  • Evidence on ozone therapy in cancer patients is lacking
  • Inhalation and direct injection can result in severe adverse effects. Safety of mixing with blood which is re-injected is not proven

Ozone (O3) is an unstable gas found in the atmosphere where it protects against solar radiation. It has been produced by specialised generators for therapeutic use.

Ozone therapy can involve body saunas, insufflation into body cavities (not the lungs), application to joints and lesions, and mixing with the patient’s blood and reinjection (autohaemotherapy). It has also been used as a disinfectant.

It has been claimed that ozone therapy has immunomodulatory and immunoactivating properties, and can correct tumour hypoxia.

In vitro and animal studies have shown changes in various biological parameters but there have been few trials in humans for any condition and no randomised controlled trials in cancer patients.

Ozone has been shown to be toxic to the lungs and dangerous if directly injected intravenously. Few adverse effects have been reported for autohaemotherapy but assessment of safety has been limited to date.

While apparently widely used, evidence on the proposed benefits in cancer patients is lacking and safety has not been proven.

Citation Karen Pilkington, CAM-Cancer Consortium. Ozone therapy [online document]. http://ws.cam-cancer.org/The-Summaries/Other-CAM/Ozone-therapy. September 11, 2013.

References

  1. Elvis AM. Ekta JS. (2011) Ozone therapy: A clinical review. Journal of Natural Science Biology & Medicine. 2(1):66-70.
  2. Bocci V.A.(2006) Scientific and Medical Aspects of Ozone Therapy. State of the Art. Archives of Medical Research. 37 (4) (pp 425-435).
  3. United States Environmental Protection Agency.(2012). Ground Level Ozone Basic Information. Available at: http://www.epa.gov/glo/basic.html. Accessed 11th September 2013.
  4. Natural Medicines Comprehensive Database: professional version. Ozone therapy monograph. Stockton (CA): Therapeutic Research Faculty. Available at: http://naturaldatabase.therapeuticresearch.com. Accessed 11th September 2013.
  5. Cassileth B. (2009) Oxygen therapies. Oncology (Williston Park). 23(13):1182.
  6. Natural Standard/Harvard Medical School (2008). Ozone therapy. Available at: http://www.intelihealth.com/IH/ihtIH/WSIHW000/8513/34968/358849.html?d=dmtContentAccessed: 20th August 2012.
  7. Burke FJ.(2012). Ozone and caries: a review of the literature. Dent Update. 39(4):271-2, 275-8.
  8. European Cooperation of Medical Ozone Societies EUROCOOP (Ärztliche Gesellschaft für Ozon-Anwendung in Prävention und Therapie). Information for patients. Available at: http://www.ozongesellschaft.de/information_for_patients_60.htm. Accessed 11th September 2013.
  9. German Medical Association of Ozone Application in Prevention and Therapy. Available at: http://www.ozonosan.de/images/upload/File/Guidelines%20OSE%201212%20published.pdf. Accessed 11st September 2013.
  10. Rubin MB. (2001). The History Of Ozone. The Schönbein Period, 1839-1868. Bull. Hist. Chem., 26 (1). Available at: http://www.scs.illinois.edu/~mainzv/HIST/awards/OPA%20Papers/2001-Rubin.pdf. Accessed 11th September 2013.
  11. American Cancer Society (2008). Pharmacological and Biological Treatment: Oxygen Therapy. Available at: http://www.cancer.org/Treatment/TreatmentsandSideEffects/ComplementaryandAlternativeMedicine/PharmacologicalandBiologicalTreatment/oxygen-therapy. Accessed: 11th September 2013.
  12. Bocci V. Biological and clinical effects of ozone. Has ozone therapy a future in medicine? Br J Biomed Sci. 1999;56(4):270-9.
  13. Bocci V. Borrelli E, Zanardi I, Travagli V. (2011). Oxygen-Ozone Therapy Is At A Cross-Road. Available at: http://www.isco3.org/files/O3_CrossRoad_Bocci_paper_2011.pdf. Accessed 11th September 2013.
  14. Sagai M., Bocci V. (2011). Med Gas Res. 2011 Dec 20;1:29. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress? Medical Gas Research. 1 (1). Article Number: 29.
  15. Bocci V., Larini A., Micheli V. (2005). Restoration of normoxia by ozone therapy may control neoplastic growth: A review and a working hypothtesis. Journal of Alternative and Complementary Medicine. 11 (2): pp 257-265.
  16. Höckel M, Vaupel P.(2001). Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 93(4):266-76.
  17. Hunt KJ, Coelho HF, Wider B, Perry R, Hung SK, Terry R, Ernst E. (2010). Complementary and alternative medicine use in England: results from a national survey. Int J Clin Pract. 64(11):1496-502. doi: 10.1111/j.1742-1241.2010.02484.x.
  18. Molassiotis A, Fernadez-Ortega P, Pud D, Ozden G, Scott JA, Panteli V, Margulies A, Browall M, Magri M, Selvekerova S, Madsen E, Milovics L, Bruyns I, Gudmundsdottir G, Hummerston S, Ahmad AM, Platin N, Kearney N, Patiraki E. (2005). Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol. 16(4):655-63. Epub 2005 Feb 2.
  19. Molassiotis A., Ozden G., Platin N., Scott J.A., Pud D., Fernandez-Ortega P., Milovics L.,Panteli V., Gudmundsdottir G., Browall M., Madsen E., Patiraki E. & Kearney N. (2006). Complementary and alternative medicine use in patients with head and neck cancers in Europe. European Journal of Cancer Care 15: 19–24.
  20. Jacobson JS, Grann VR, Gnatt MA, Hibshoosh H, Austin JH, Millar WS, Neugut AI. (2005). Cancer outcomes at the Hufeland (complementary/alternative medicine) klinik: a best-case series review. Integr Cancer Ther. 4(2):156-67.
  21. United States Food and Drug Administration. (2012). Title 21--Food And Drugs.Chapter I--Food And Drug Administration Department Of Health And Human Services. Subchapter H--Medical Devices. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=801.415. Accessed 11th September 2013.
  22. Magalhaes FN, Dotta L, Sasse A, Teixera MJ, Fonoff ET. Ozone therapy as a treatment for low back pain secondary to herniated disc: a systematic review and meta-analysis of randomized controlled trials. Pain Physician. 2012 Mar-Apr;15(2):E115-29.
  23. Rickard GD, Richardson R, Johnson T, McColl D, Hooper L. Ozone therapy for the treatment of dental caries. Cochrane Database Syst Rev. 2004;(3):CD004153.
  24. Re L, Mawsouf MN, Menéndez S, León OS, Sánchez GM, Hernández F. Ozone therapy: clinical and basic evidence of its therapeutic potential. Arch Med Res. 2008 Jan;39(1):17-26. Epub 2007 Sep 29.
  25. Muller-Tyl E, Salzer H, Reisinger L, Washuttl J, Wurst F. [Ozone-oxygen therapy for gynecologic carcinomas. The effect of parenteral-ozone oxygen mixture administration on free fatty acids and triglycerides in patients with gynecologic carcinomas]. Fortschr Med 1979; 97(10):451-454.
  26. Enzelsberger H, Metka M, Salzer H. [Effect of a parenteral ozone-oxygen mixture on the concentration of immunoglobulins (IgA, IgG, IgM), of vitamin A and lysozyme activity in patients with cervical cancer]. Geburtshilfe Frauenheilkd 1987; 47(12):343-345.
  27. Clavo B, Pérez JL, López L, Suárez G, Lloret M, Rodríguez V, Macías D, Santana M, Hernández MA, Martín-Oliva R, Robaina F. Ozone Therapy for Tumor Oxygenation: a Pilot Study. Evid Based Complement Alternat Med. 2004 Jun 1;1(1):93-98.
  28. Janssen HL, Haustermans KM, Balm AJ, Begg AC. Hypoxia in head and neck cancer: how much, how important? Head Neck. 2005 Jul;27(7):622-38.
  29. Buffa FM, Harris AL, West CM, Miller CJ. Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene. Br J Cancer. 2010 Jan 19;102(2):428-35. Erratum in: Br J Cancer. 2010 Sep 7;103(6):929.
  30. Clavo B, Ruiz A, Lloret M, López L, Suárez G, Macías D, Rodríguez V, Hernández MA, Martín-Oliva R, Quintero S, Cuyás JM, Robaina F. Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study. Evid Based Complement Alternat Med. 2004 Dec;1(3):321-325. Epub 2004 Oct 16.
  31. Parkhisenko I, Bil'chenko SV.(2003). [The ozone therapy in patients with mechanical jaundice of tumorous genesis]. Vestn Khir Im I I Grek 162(5):85-87.
  32. Clavo B, Gutierrez D, Martin D, Suarez G, Hernandez MA, Robaina F. (2005). Intravesical ozone therapy for progressive radiation-induced hematuria. J Altern Complement Med 11(3):539-541.
  33. Subbotin VM, Zitta DV, Terekhina NA. (2007)[Prophylaxis of acute postoperative gastroduodenal ulcers at the patients with colorectal cancer]. Khirurgiia (Mosk) (3):4-6.
  34. Petrucci MT, Gallucci C, Agrillo A, Mustazza MC, Foa R. (2007). Role of ozone therapy in the treatment of osteonecrosis of the jaws in multiple myeloma patients. Haematologica 92(9):1289-1290.
  35. Ripamonti CI, Cislaghi E, Mariani L, Maniezzo M. (2011). Efficacy and safety of medical ozone (O(3)) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: Preliminary results of a phase I-II study. Oral Oncol 47(3):185-190.
  36. Clavo B, Ceballos D, Gutierrez D, Rovira G, Suarez G, Lopez L, Pinar B, Cabezon A, Morales V, Oliva E, Fiuza MD, Santana-Rodriguez M. Long-term control of refractory hemorrhagic radiation proctitis with ozone therapy.J Pain Symptom Manage. 2013 Jul;46(1):106-12.
  37. Grundner HG, Erler U. [Animal experiments on ozone therapy of non-irradiated and irradiated tumors. II. Ehrlich ascites carcinoma in vivo]. Strahlentherapie 1976; 151(6):522-529.
  38. Schulz S, Haussler U, Mandic R, Heverhagen JT, Neubauer A, Dunne AA et al. Treatment with ozone/oxygen-pneumoperitoneum results in complete remission of rabbit squamous cell carcinomas. Int J Cancer 2008; 122(10):2360-2367.
  39. Kesik V., Uysal B., Kurt B., Kismet E., Koseoglu V. Cancer Biology and Therapy. 8 (17) (pp 1623-1628), 2009.
  40. Sweet F, Kao MS, Lee SC, Hagar WL, Sweet WE. Ozone selectively inhibits growth of human cancer cells. Science 1980; 209(4459):931-933.
  41. Karlic H, Kucera H, Metka M, Schonbauer M, Soregi G. [Effect of ozone and ionizing radiation on an in vitro model--a pilot study of 4 gynecologic tumors]. Strahlenther Onkol 1987; 163(1):37-42.
  42. Bocci V, Luzzi E, Corradeschi F, Silvestri S. Studies on the biological effects of ozone: 6. Production of transforming growth factor 1 by human blood after ozone treatment. J Biol Regul Homeost Agents 1994; 8(4):108-112.
  43. Zanker KS, Kroczek R. In vitro synergistic activity of 5-fluorouracil with low-dose ozone against a chemoresistant tumor cell line and fresh human tumor cells. Chemotherapy 1990; 36(2):147-154.
  44. Bucci B., Cannizzaro A., Brunetti E., Martinelli M. Ozone treatment inhibits proliferation in human neuroblastoma SK-N-SH cells. Rivista Italiana di Ossigeno-Ozonoterapia. 5 (2) (pp 85-92), 2006.
  45. Jerrett M, Burnett RT, Pope CA 3rd, Ito K, Thurston G, Krewski D, Shi Y, Calle E, Thun M. Long-term ozone exposure and mortality. N Engl J Med. 2009 Mar 12;360(11):1085-95.
  46. Faustini A, Capobianchi MR, Martinelli M, Abbate I, Cappiello G, Perucci CA. A cluster of hepatitis C virus infections associated with ozone-enriched transfusion of autologous blood in Rome, Italy. Infect Control Hosp Epidemiol. 2005 Sep;26(9):762-7.
  47. Ripamonti CI, Maniezzo M, Pessi MA, Boldini S. Treatment of osteonecrosis of the jaw (ONJ) by medical ozone gas insufflation. A case report. Tumori. 2012 May-Jun;98(3):72e-75e.