Ozone therapy

File:Ozone for dental application.jpg

Ozone therapy consists of the introduction of ozone into the body via various methods, usually involving its mixture with various gases and liquids before injection, with potential routes including the vagina, rectum, into a muscle, under the skin, or directly into a vein. Ozone can also be introduced via autohemotherapy, in which blood is drawn from the patient, exposed to ozone, and re-injected into the patient.{{cite web |title=Oxygen Therapy |url=http://www.cancer.org/Treatment/TreatmentsandSideEffects/ComplementaryandAlternativeMedicine/PharmacologicalandBiologicalTreatment/oxygen-therapy |archive-url=https://web.archive.org/web/20100721031010/http://www.cancer.org/Treatment/TreatmentsandSideEffects/ComplementaryandAlternativeMedicine/PharmacologicalandBiologicalTreatment/oxygen-therapy |archive-date=21 July 2010 |access-date=29 November 2012 |publisher=American Cancer Society}}

This therapy has been proposed as a primary or adjunct therapy for various diseases, including osteoarthritis,{{cite journal |last1=Arias-Vázquez |first1=Pedro Iván |last2=Tovilla-Zárate |first2=Carlos Alfonso |last3=Hernández-Díaz |first3=Yazmín |last4=González-Castro |first4=Thelma Beatriz |last5=Juárez-Rojop |first5=Isela Esther |last6=López-Narváez |first6=María Lilia |last7=Bermudez-Ocaña |first7=Deysi Yadira |last8=Barjau-Madrígal |first8=Hugo Adrián |last9=Legorreta-Ramírez |first9=Gabriela |title=Short-Term Therapeutic Effects of Ozone in the Management of Pain in Knee Osteoarthritis: A Meta-Analysis |journal=PM&R |date=30 May 2019 |volume=11 |issue=8 |pages=879–887 |doi=10.1002/pmrj.12088 |pmid=30689297 |s2cid=59307186 }}{{cite journal |last1=Raeissadat |first1=Seyed Ahmad |last2=Tabibian |first2=Elnaz |last3=Rayegani |first3=Seyed Mansoor |last4=Rahimi-Dehgolan |first4=Shahram |last5=Babaei-Ghazani |first5=Arash |title=An investigation into the efficacy of intra-articular ozone (O₂–O₃) injection in patients with knee osteoarthritis: a systematic review and meta-analysis |journal=Journal of Pain Research |date=October 2018 |volume=11 |pages=2537–2550 |doi=10.2147/JPR.S175441 |pmid=30498370 |pmc=6207244 |doi-access=free }}{{cite journal |last1=Noori-Zadeh |first1=Ali |last2=Bakhtiyari |first2=Salar |last3=Khooz |first3=Roghayeh |last4=Haghani |first4=Karimeh |last5=Darabi |first5=Shahram |title=Intra-articular ozone therapy efficiently attenuates pain in knee osteoarthritic subjects: A systematic review and meta-analysis |journal=Complementary Therapies in Medicine |date=1 February 2019 |volume=42 |pages=240–247 |doi=10.1016/j.ctim.2018.11.023 |pmid=30670248 |s2cid=58951422 }} herniated disk,{{cite journal |last1=Steppan |first1=Jim |last2=Meaders |first2=Thomas |last3=Muto |first3=Mario |last4=Murphy |first4=Kieran J. |title=A Metaanalysis of the Effectiveness and Safety of Ozone Treatments for Herniated Lumbar Discs |journal=Journal of Vascular and Interventional Radiology |date=1 April 2010 |volume=21 |issue=4 |pages=534–548 |doi=10.1016/j.jvir.2009.12.393 |pmid=20188591 }} chronic wounds,{{cite journal |last1=Fitzpatrick |first1=Erin |last2=Holland |first2=Olivia J |last3=Vanderlelie |first3=Jessica J |title=Ozone therapy for the treatment of chronic wounds: A systematic review |journal=International Wound Journal |date=August 2018 |volume=15 |issue=4 |pages=633–644 |doi=10.1111/iwj.12907 |pmid=29536625 |pmc=7949634 |s2cid=3855845 }} hepatitis B{{cite journal |last1=Cespedes-Suarez |first1=Javier |last2=Martin-Serrano |first2=Yanisley |last3=Carballosa-Peña |first3=Maria Rosa |last4=Dager-Carballosa |first4=Diana Rosa |title=Response of patients with chronic Hepatitis B in one year of treatment with Major Autohemotherapy. |journal=Journal of Ozone Therapy |date=15 December 2018 |volume=2 |issue=3 |doi=10.7203/jo3t.2.3.2018.11459 |s2cid=196554051 |doi-access=free |hdl=10550/72124 |hdl-access=free }}{{cite journal |last1=Jiao |first1=XJ |last2=Peng |first2=X |title=Clinilal study of medical ozone therapy in chronic hepatitis B of 20 patients |journal=Zhonghua Shi Yan He Lin Chuang Bing du Xue Za Zhi = Zhonghua Shiyan He Linchuang Bingduxue Zazhi = Chinese Journal of Experimental and Clinical Virology |date=December 2008 |volume=22 |issue=6 |pages=484–5 |pmid=19544653 }} and C,{{cite journal |last1=Zaky |first1=Saad |last2=Kamel |first2=Sherif Ebrahiem |last3=Hassan |first3=Magda Shahata |last4=Sallam |first4=Nadia Abdel |last5=Shahata |first5=Mohamad Ahmad |last6=Helal |first6=Shaaban Redwan |last7=Mahmoud |first7=Heba |title=Preliminary Results of Ozone Therapy as a Possible Treatment for Patients with Chronic Hepatitis C |journal=The Journal of Alternative and Complementary Medicine |date=March 2011 |volume=17 |issue=3 |pages=259–263 |doi=10.1089/acm.2010.0016 |pmid=21417811 }}{{cite journal |last1=Mawsouf |first1=M.N. |last2=Tanbouli |first2=T.T. |last3=Viebahn-Hänsler |first3=R. |title=Ozone Therapy in Patients with Viral Hepatitis C: Ten Years' Experience |journal=Ozone: Science & Engineering |date=November 2012 |volume=34 |issue=6 |pages=451–458 |doi=10.1080/01919512.2012.720161 |bibcode=2012OzSE...34..451M |s2cid=96088027 }} herpes zoster,{{cite journal |last1=Huang |first1=Jian |last2=Xiang |first2=Yaping |last3=Gao |first3=Lihua |last4=Pan |first4=Yizhi |last5=Lu |first5=Jianyun |last6=Huang |first6=Jinhua |date=28 February 2018 |title=[Topical ozone therapy: An innovative solution to patients with herpes zoster]. |journal=Zhong Nan da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences |volume=43 |issue=2 |pages=168–172 |doi=10.11817/j.issn.1672-7347.2018.02.011 |pmid=29559601}} HIV-AIDS,{{cite journal |last1=Cespedes-Suarez |first1=Javier |last2=Martin-Serrano |first2=Yanisley |last3=Carballosa-Peña |first3=Maria Rosa |last4=Dager-Carballosa |first4=Diana Rosa |title=The immune response behavior in HIV-AIDS patients treated with Ozone therapy for two years. |journal=Journal of Ozone Therapy |date=15 December 2018 |volume=2 |issue=3 |doi=10.7203/jo3t.2.3.2018.11458 |s2cid=196563719 |doi-access=free |hdl=10550/72131 |hdl-access=free }} multiple sclerosis,{{cite journal |last1=Delgado-Roche |first1=Livan |last2=Riera-Romo |first2=Mario |last3=Mesta |first3=Fernando |last4=Hernández-Matos |first4=Yanet |last5=Barrios |first5=Juan M. |last6=Martínez-Sánchez |first6=Gregorio |last7=Al-Dalaien |first7=Said M. |title=Medical ozone promotes Nrf2 phosphorylation reducing oxidative stress and pro-inflammatory cytokines in multiple sclerosis patients |journal=European Journal of Pharmacology |date=September 2017 |volume=811 |pages=148–154 |doi=10.1016/j.ejphar.2017.06.017 |pmid=28623000 }} cancer, heart disease, Alzheimer's dementia, and Lyme disease, though supportive evidence for some of these applications is limited. The American Cancer Society warned in 2010 that evidence for the efficacy of ozone therapy against cancer is inconclusive, and the therapy may be dangerous. For treatment of HIV/AIDS, although ozone deactivates the viral particles in vitro, well-designed studies have shown there is no benefit for living patients.{{cite web |url = http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/oxygen.html | author-link=Saul Green| title=Oxygenation Therapy: Unproven Treatments for Cancer and AIDS| publisher=Scientific Review of Alternative Medicine | year = 1997 | vauthors = Green S }}

The United States Food and Drug Administration initially stated in 1976, and reiterated its position in 2006, that when inhaled, ozone is a toxic gas that has no demonstrated safe medical application, though their position statements primarily deal with its potential for causing inflammation and pulmonary edema in the lungs. They also emphasize that for ozone to be effective as a germicide, it must be present at concentrations far greater than can be safely tolerated by humans or other animals.{{cite web | url = http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=801.415 | title = Code of Federal Regulations, Title 21 Vol 8 section 801.415 | date = 1 April 2011 | access-date = 4 October 2011 | publisher = Food and Drug Administration}} More recent reviews have highlighted that different routes of administration may result in different therapeutic and side-effect profiles.

Some reviews have suggested ozone as a potential treatment for herniated discs{{cite journal | vauthors = Steppan J, Meaders T, Muto M, Murphy KJ | title = A meta-analysis of the effectiveness and safety of ozone treatments for herniated lumbar discs | journal = Journal of Vascular and Interventional Radiology | volume = 21 | issue = 4 | pages = 534–48 | date = April 2010 | pmid = 20188591 | doi = 10.1016/j.jvir.2009.12.393 }} and diabetic neuropathy.{{cite journal | vauthors = Braidy N, Izadi M, Sureda A, Jonaidi-Jafari N, Banki A, Nabavi SF, Nabavi SM | title = Therapeutic relevance of ozone therapy in degenerative diseases: Focus on diabetes and spinal pain | journal = Journal of Cellular Physiology | volume = 233 | issue = 4 | pages = 2705–2714 | date = April 2018 | pmid = 28594115 | doi = 10.1002/jcp.26044 | s2cid = 10266228 }} There is some controversy about its use by athletes to increase performance despite numerous adverse side effects within the pulmonary and/or skeletal muscle systems. Although its use is not disallowed in and of itself, it can be mixed with banned substances for administration prior to injection.{{cite web|url=http://www.cyclingnews.com/news/belgian-court-continuing-investigation-of-ozone-therapy-doctor |title=Belgian Court Continuing Investigation Of Ozone-therapy Doctor |publisher=Cycling News |date=9 February 2013 |access-date=10 February 2013}}

Ozone therapy has potentially serious adverse effects, and {{as of|lc=yes|2012}} at least five deaths had been reported due to the therapy's use on people with cancer.{{cite journal |vauthors=Cassileth BR, Yarett IR |title=Cancer quackery: the persistent popularity of useless, irrational 'alternative' treatments |journal=Oncology (Williston Park, N.Y.) |volume=26 |issue=8 |pages=754–8 |date=August 2012 |pmid=22957409 |type=Review}} From 1975 to 1983 in Germany, research revealed six deaths, four cases of visual disturbance, three cases of paraplegias, four gas embolisms in the pulmonary circuit, two myocardial infarction, four pulmonary embolisms, two cases of apoplexy paralysis, and two cases of cardiac arrhythmia following ozone therapy. More commonly, pulmonary edema is the most prevalent adverse effect of ozone treatment. In the muscular system, many cases of tendon rupture, osteoarthritis, myositis, synovitis, joint infections, and muscle tears have been documented as results of ozone therapy. In the integumentary system, benign skin discoloration is most common. These all occurred following direct injection of O₂/O₃ gas: a method now regarded as malpractice by most ozone practitioners. In each case, the clinical picture corresponded either to gas embolism, or allergic shock. The fact that one case of apparent allergic shock followed the injection of a minute quantity of gas raises the unknown possibility that other methods of administration might also carry the risk of allergic shock.{{cite book |date=2001-03-30 |title=Ozon-Therapie, Ozon-Eigenbluttherapie, Sauerstoff-OzonEigenbluttherapie, Oxyontherapie, Hyperbare Ozontherapie: Zusammenfassender Bericht des Arbeitsausschusses "Ärztliche Behandlung" des Bundesausschusses der Ärzte und Krankenkassen |trans-title=Ozone therapy, Autologous ozone blood therapy, Oxygen-ozone autologous blood therapy, Oxyon therapy, Hyperbaric ozone therapy: Summary report of the "Medical Treatment" Working Committee of the Federal Committee of Doctors and Health Insurance Companies |url=https://www.g-ba.de/downloads/40-268-248/HTA-Ozon-Therapie.pdf |language=de |publisher=Geschäftsführung des Arbeitsausschusses "Ärztliche Behandlung" des Bundesausschusses der Ärzte und Krankenkassen}} pp 17-18.Eisenmenger W. Zur Ozontherapie. In: Oepen I, Prokop O, editors. Außenseitermethoden in der Medizin. Ursprünge, Gefahren, Konsequenzen. Darmstadt. Darmstadt: 1986, 195-220. https://core.ac.uk/reader/12167629

Much of the concern related to ozone therapy revolves around the safety of blood ozonation. When inhaled by mammals in high levels, ozone reacts with compounds in tissues lining the lungs and triggers a cascade of pathological effects, including pulmonary edema, however, ozone therapy does not usually involve inhalation of ozone gas.{{cite journal | vauthors = Zanardi I, Borrelli E, Valacchi G, Travagli V, Bocci V | title = Ozone: A Multifaceted Molecule with Unexpected Therapeutic Activity | journal = Current Medicinal Chemistry | volume = 23 | issue = 4 | pages = 304–14 | date = 2016 | pmid = 26687830 | doi = 10.2174/0929867323666151221150420 | hdl = 11365/998522 | hdl-access = free }}{{cite journal | vauthors = Bocci V, Borrelli E, Travagli V, Zanardi I | title = The ozone paradox: ozone is a strong oxidant as well as a medical drug | journal = Medicinal Research Reviews | volume = 29 | issue = 4 | pages = 646–82 | date = July 2009 | pmid = 19260079 | doi = 10.1002/med.20150 | s2cid = 206250706 | hdl = 11365/8222 | hdl-access = free }} It has been argued that while peroxides (a product of ozone) are naturally generated inside phagocyte cells to kill bacteria, outside the cell they can damage tissue.{{cite web |url = http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/oxygen.html | author=Green S | title=Oxygenation therapy: Unproven treatments for Cancer and AIDS | date=17 June 2001 | website=Quackwatch }} Proponents suggest that its effects are tissue-dependent, though the subject is still debated.{{cite journal | vauthors = Bocci V, Zanardia I, Valacchi G, Borrelli E, Travagli V | title = Validity of Oxygen-Ozone Therapy as Integrated Medication Form in Chronic Inflammatory Diseases | journal = Cardiovascular & Hematological Disorders Drug Targets | volume = 15 | issue = 2 | pages = 127–38 | date = 2015 | pmid = 26126818 | doi = 10.2174/1871529x1502151209114642 | hdl = 11365/1000206 | hdl-access = free }}

Other serious incidents reported include transmission of hepatitis C.{{cite journal | vauthors = Ernst E | title = A primer of complementary and alternative medicine commonly used by cancer patients | journal = The Medical Journal of Australia | volume = 174 | issue = 2 | pages = 88–92 | date = January 2001 | pmid = 11245510 | doi = 10.5694/j.1326-5377.2001.tb143161.x| s2cid = 45055625 | url = http://www.mja.com.au/public/issues/174_02_150101/ernst/ernst.html }} [citation requires membership to industry magazine]. This article also reports 5 fatalities, which are included in the six fatalities reported by Eisenmenger (1986). Ozone-based treatments can be associated with central nervous system toxicity, termed Ozone Induced Encephalopathy (OIE).{{cite journal |vauthors=Haggiag S, Prosperini L, Stasolla A, Gerace C, Tortorella C, Gasperini C |title=Ozone-induced encephalopathy: A novel iatrogenic entity |journal=Eur J Neurol |volume= 28|issue= 8|pages= 2471–2478|date=March 2021 |pmid=33657263 |doi=10.1111/ene.14793 |s2cid=232114612 |url=}}

The FDA prohibits the medical use of ozone "in any medical condition for which there is no proof of safety and effectiveness", stating that "ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. For ozone to be germicidal, it must be present in a concentration far greater than that which can be safely tolerated by man and animals."[https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-801/subpart-H/section-801.415 Code of Federal Regulations Title 21] Sec. 801.415 Maximum acceptable level of ozone (FDA Website, as of 2022-07-18)

Beginning in 1991 the FDA has prosecuted and sent to jail several people presenting themselves as medical doctors and selling ozone therapy products as a medical cure or operating medical clinics using ozone therapy for healing human illness.{{cite news|last1=Knotts|first1=Bob | name-list-style = vanc |title=Judge Won't Reduce Bail For Ozone Therapy Advocate|url=http://articles.sun-sentinel.com/1990-10-19/news/9002200233_1_ozone-previous-arrest-fraud|archive-url=https://web.archive.org/web/20151023072409/http://articles.sun-sentinel.com/1990-10-19/news/9002200233_1_ozone-previous-arrest-fraud|url-status=dead|archive-date=23 October 2015|access-date=1 May 2018|publisher=The Sentinel Sun|date=19 October 1990}}{{cite book|last1=Whitlock|first1=Chuck |title=MediScams: how to spot and avoid health care scams, medical frauds, and quackery from the local physician to the major health care providers and drug manufacturers |date=2001 |publisher=Renaissance Books |isbn=978-1-58063-180-8 |page=139 |edition= 1st }} Arrests following similar activity have been made in other countries as well, including Uganda and Thailand.{{cite news|last1=Malaba|first1=Tom|last2=Kiwanuka|first2=Christopher| name-list-style = vanc |title=Ozone Therapy Lands Kampala Doctor in Trouble|url=https://ugandaradionetwork.com/story/ozone-therapy-lands-kampala-doctor-in-trouble|access-date=1 May 2018|publisher=Uganda Radio Network|date=15 December 2008}}{{cite news|title=Woman who sought Thai "Ozone Therapy" dies|url=http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10400153|access-date=1 May 2018|publisher=The New Zealand Herald|date=7 September 2006}}

Ozone therapy is sold as an expensive alternative cancer treatment in Germany. David Gorski has described the practice as "pure quackery".{{cite web |first=David |last=Gorski |url=https://sciencebasedmedicine.org/german-alternative-cancer-clinics/ |publisher=Science-Based Medicine |title=German alternative cancer clinics: Combining experimental therapeutics with rank quackery and charging big bucks for it |date=24 October 2016}} Proponents of the therapy falsely claim it is a recognized therapy there, but the German medical establishment has not approved ozone therapy.

In 2009, a panel of experts consulted by Forbes recommended that ozone therapy be included on a "list of the most egregious, dangerous, aggressively marketed health scams."{{cite news |last1=Detwiler |first1=Jacqueline |title=Most Dangerous Health Scams |url=https://www.forbes.com/2009/01/03/dangerous-health-scams-forbeslife-cx_jd_0105health.html |work=Forbes |date=5 January 2009}}

Ozone therapy was banned in Malaysia in 2017. The Malaysian Health Ministry determined that the treatment could cause serious harm and had no scientific support as a treatment for any condition.{{cite news |last1=Kannan |first1=Hashini Kavishtri |title=Ozone therapy treatments now banned in Malaysia |url=https://www.nst.com.my/news/government-public-policy/2017/05/236163/ozone-therapy-treatments-now-banned-malaysia |access-date=27 December 2023 |publisher=New Straits Times |date=3 May 2017 }}

On 7 August 2023, the Brazilian government legalized ozone therapy as a complementary therapy, ignoring a request for veto due to lack of scientific evidence made in an open letter from the Brazilian National Academy of Medicine.{{cite news |title=Lula sanciona lei que autoriza ozonioterapia no Brasil; texto diz que tratamento é complementar |url=https://www.cnnbrasil.com.br/saude/lula-sanciona-lei-que-autoriza-ozonioterapia-no-brasil-texto-diz-que-tratamento-e-complementar/ |access-date=7 August 2023 |date=7 August 2023 |language=Portuguese |trans-title=Lula signs law authorizing ozone therapy in Brazil; text states that the treatment is complementary}}

In 1856, just 16 years after its discovery, ozone was first used in a healthcare setting to disinfect operating rooms and sterilize surgical instruments.Chemical Technology Encyclopedia; Barnes & Noble 1968 vol.1 pp.82–83 By the end of the 19th century the use of ozone to disinfect drinking water of bacteria and viruses was well established in mainland Europe.{{cite journal | vauthors = Suchkov BP | title = [Study of the ozonization of drinking water containing pathogenic bacteria and viruses] | language = ru | journal = Gigiena i Sanitariia | volume = 29 | pages = 22–9 | date = June 1964 | pmid = 14235449 }}

In 1892 The Lancet published an article describing the administration of ozone for treatment of tuberculosis.{{cite journal | title = The Internal Administration of Ozone in the Treatment of Phthisis | journal = Lancet | volume = 140 | issue = 3612 | year = 1892 | pages = 1180–1181 |doi=10.1016/S0140-6736(01)92422-5}} During World War I, ozone was tested at Queen Alexandra Military Hospital in London as a possible disinfectant for wounds. The gas was applied directly to wounds for as long as 15 minutes. This resulted in damage to both bacterial cells and human tissue. Other sanitizing techniques, such as irrigation with antiseptics, were preferable.{{cite journal|last1= Jacewicz |first1=Natalie | name-list-style = vanc |title=A Killer of a Cure |journal=Distillations |date=2017|volume=3|issue=1 |pages=34–37 |url=https://www.sciencehistory.org/distillations/magazine/a-killer-of-a-cure|access-date=13 April 2018}}{{cite journal |last=Stoker |first=George | name-list-style = vanc | title=The Surgical Uses of Ozone| journal =Lancet |volume=188 |issue=4860 | year = 1916 | page = 712 |doi=10.1016/S0140-6736(01)31717-8}}

The psychoanalyst Wilhelm Reich was a proponent of ozone therapy, which was supposed to enhance an imaginary life force he called orgone. Reich developed a device utilizing ozonides in his work on bioenergetic analysis.{{Cite web |last=MazzocchI |first=Alberto |title=A Preliminary Study of the Reich Orgone Accumulator Effects on Human Physiology |url=https://journals.sfu.ca/seemj/index.php/seemj/article/viewFile/452/413}}

• Ozone health effects
• Air ioniser
• List of unproven and disproven cancer treatments

{{Reflist}}

• [https://www.epa.gov/indoor-air-quality-iaq/ozone-generators-are-sold-air-cleaners Ozone Generators that are Sold as Air Cleaners] - factsheet at US EPA

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