Ozone Therapy

Discovery and early medical use

A 2025 historical review dates the first observation of ozone to 1785, when the Dutch physicist Martin van Marum noticed a distinctive smell while passing electricity through oxygen, and credits Christian Friedrich Schönbein with naming the gas in 1840. The same review records an ozonizing device for water purification built by Werner von Siemens in 1857, ozone steam baths used by John Harvey Kellogg at his sanitarium from 1880, and an ozone generator patented by Nikola Tesla in 1896, a patent also noted in a 2011 clinical review.

Both reviews state that physicians applied ozone to infected wounds during the First World War (1914 to 1918). The 2025 review dates the first use of rectal insufflation to the French physician Paul Aubourg in 1936 and links a decline of ozone use in the United States to opposition from the American Medical Association in 1933. These accounts rely largely on secondary literature and are written by authors sympathetic to the practice.

Postwar development and international societies

According to the 2025 review, Hans Wolff opened an ozone therapy training school in Germany in 1953 and introduced major and minor autohemotherapy around 1961, working with Joachim Hänsler, whose ozone generator dates to 1957 and 1958; the two co-founded a German ozone therapy association in 1972. The review also describes research centers in the Soviet Union and Cuba, and the founding in 2010 of an international scientific body for ozone therapy (ISCO3), which issued the Madrid Declaration on Ozone Therapy that year.

The 2011 review reports that in the late 1980s German physicians described treating people with HIV using ozone autohemotherapy, and that a subsequent Canadian study found the procedure ineffective as a treatment for AIDS. The history of ozone therapy therefore includes both expansion through professional societies and early claims that controlled testing did not support.

Ozone, medical ozone and oxygen-ozone

Ozone (O3) is a molecule of three oxygen atoms. A 2011 review describes it as an unstable, colorless gas with an acrid smell and a half-life of about 40 minutes at 20°C. An evidence summary from the CAM-Cancer project explains that medical ozone is produced by passing oxygen through a high-voltage field, so the gas delivered is a mixture of oxygen and ozone rather than pure ozone. A 2025 review gives typical concentrations of 0.5% to 5% ozone in the mixture.

The labels 'ozone therapy', 'oxygen-ozone therapy' and 'medical ozone' are used largely interchangeably in the literature, and one review uses 'oxy-ozone therapy'. These names cover procedures with very different routes, doses and risks, so a finding about one procedure says little about another.

Names of specific procedures

Autohemotherapy (spelled autohaemotherapy in British sources) refers to drawing a person's blood, exposing it to the gas mixture and reinfusing it; a 'major' form and a 'minor' form are distinguished in the literature. Rectal insufflation introduces the gas into the rectum. Injection of the gas into an intervertebral disc is called intradiscal ozone therapy, and case reports also use the terms oxygen-ozone chemonucleolysis and ozone discolysis. Paravertebral injection places the gas in the muscles beside the spine. Ozonated oil and ozonated water are carriers used on skin, wounds and in the mouth.

Routes of administration

The CAM-Cancer summary lists local treatments, rectal insufflation, ozonated water, autohemotherapy, and nasal, oral, vaginal and skin applications among the routes in use. Because ozone is a gas, special techniques have been devised to contain it. The 2011 review describes a transcutaneous gas bath in which a limb is enclosed at low pressure in a closed system, and ozonated water applied as a spray or compress in dentistry. The same review states that medical ozone is never given by inhalation.

Spinal and joint injections

For low back pain linked to a herniated disc, clinicians inject the gas percutaneously, either into the disc itself or into the paravertebral muscles, usually under imaging guidance. A 2012 systematic review notes that many studies combined ozone with other injected agents such as corticosteroids or local anesthetics. One case report describes the stated aim of intradiscal injection as dehydrating the disc and altering its contents. Ozone is also injected into the knee joint for osteoarthritis.

Settings and practitioner standards

Ozone therapy is offered by physicians in pain and spine clinics, by dentists, and by naturopathic and integrative practitioners, with practice varying by country. ISCO3 publishes the Madrid Declaration, a professional consensus document whose second edition (2015) contains a section on basic rules for training in ozone therapy and lists direct intravenous injection of ozone and intra-arterial injection among routes it treats as not acceptable. The declaration is a document of a body that promotes the therapy, not an independent standard, and the sources reviewed do not establish a common training requirement across countries.

Uses described by proponents

Proponents attribute antimicrobial, antioxidant, anti-inflammatory and immune-modulating effects to medical ozone, and propose that it stimulates oxygen metabolism. A 2011 review lists infected wounds, circulatory disorders, age-related conditions, macular degeneration, viral infections, arthritis, cancer, SARS and AIDS among the conditions treated. A 2025 review adds wound healing and adjuvant cancer therapy. These lists describe how the therapy is promoted; they are not findings of effectiveness, and proposed mechanisms have mostly been studied in the laboratory.

Uses that have been studied in trials

Controlled trials and systematic reviews have examined a narrower set of uses: dental caries, chronic periodontitis and recovery after wisdom-tooth surgery; diabetic foot ulcers; knee osteoarthritis; low back pain from herniated discs; COVID-19; and quality of life during cancer treatment. Each use involves a different route and dose, and evidence for one cannot be carried over to another.

Overview across conditions

A 2026 umbrella review found seven meta-analyses of randomized trials of ozone therapy, covering chronic periodontitis, COVID-19, diabetic foot ulcers and impacted lower third-molar surgery. Certainty of evidence was low or very low for every outcome. For COVID-19, ozone reduced PCR positivity (risk ratio 0.07), which the authors judged a surrogate of little clinical importance, with no benefit for hospital stay, intensive care admission or mortality. Adverse events were inconsistently reported, and the authors concluded that routine clinical use is not justified pending adequately powered, blinded trials.

Dental caries and diabetic foot ulcers

A Cochrane review of ozone for dental caries, with searches to 2003, included three trials with 432 randomized lesions in 137 participants. All were judged at high risk of bias, effects were inconsistent across outcome measures, and the authors found no reliable evidence that ozone gas applied to decayed teeth stops or reverses decay. Cochrane withdrew the review in 2019 because it was out of date and not a priority for updating, while stating that it was correct when published.

A 2015 Cochrane review of diabetic foot ulcers included three small trials (212 participants). In one trial of 101 people, ozone compared with antibiotics was associated with a greater reduction in ulcer area and a shorter hospital stay but no difference in the number of ulcers healed at 20 days. Two trials (111 people) comparing ozone plus usual care with usual care alone found no clear difference in ulcer area, healing, adverse events or amputation. The authors could not draw firm conclusions.

Herniated discs and knee osteoarthritis

A 2012 systematic review of percutaneous ozone for low back pain from disc herniation included four randomized trials in a meta-analysis and eight observational studies. The trials mainly compared ozone with other active treatments, no placebo-controlled trial was found, and many studies mixed ozone with other drugs; the authors nonetheless judged the results positive. A 2024 meta-analysis reported higher treatment success with intradiscal ozone than with steroid injections at six months (odds ratio 3.95) and greater pain reduction than with oral medicines, with outcomes similar to microdiscectomy at 18 months.

For knee osteoarthritis, a 2024 umbrella review rated all eight included systematic reviews (15 trials) as critically low in confidence. Three reported reduced pain compared with placebo, five found ozone not superior to other treatments, and effects on joint function were less consistent.

Cancer

The CAM-Cancer evidence summary, updated in November 2025, found only one randomized trial in cancer published in full in English and seven controlled trials available only as abstracts, with most of the literature consisting of laboratory studies, animal studies and case reports. No survival benefit has been shown. Some small studies reported improvements in quality of life or symptoms, but the summary describes the evidence as inconsistent and of limited methodological quality.

Gas embolism, stroke and deaths

Case reports describe serious harms when gas enters the circulation. A 2000 forensic report described a death from gas embolism during oxygen-ozone autohemotherapy given for psoriasis. A 2019 report described a suspected massive pulmonary embolism followed by sudden death in an older woman treated for disc-related low back pain; the authors believed the needle had accidentally punctured a vein during intradiscal injection. A 2024 report described cerebral gas embolism and multiple strokes in a 58-year-old woman during lumbar intradiscal injection; she had a patent foramen ovale, a heart opening that can let gas bubbles reach the brain, and had improved substantially a year later.

The CAM-Cancer summary describes such events as rare but documented, listing ischemic stroke, pulmonary embolism with death, an encephalopathy syndrome and fatal septic shock after injections. Case reports cannot show how often these events occur.

Infection after spinal injection

Infection of the disc and spine has been reported after intradiscal treatment. A 2014 report described a 29-year-old woman who developed chronic osteomyelitis and septic discitis at the lowest lumbar level after oxygen-ozone therapy, caused by an environmental bacterium, and who needed spinal fusion surgery; the authors identified it as the third published report of spinal infection after intradiscal oxygen-ozone treatment in the English-language literature at that time. Sterile technique and equipment matter for any injected procedure.

Lungs, common effects and precautions

Ozone is a recognized respiratory toxicant in photochemical smog. The 2011 review states that medical ozone is never given by inhalation, and the CAM-Cancer summary notes that inhalation can cause respiratory problems. Common, usually short-lived effects reported with ozone therapy include fatigue, headache, nausea, flu-like symptoms, local irritation and dizziness. CAM-Cancer advises against direct intravenous injection of the gas, a route the Madrid Declaration also lists as not acceptable.

Precautions noted by CAM-Cancer include glucose-6-phosphate dehydrogenase (G6PD) deficiency and pregnancy or breastfeeding, where data are mixed. No interactions with medicines are established, though theoretical concerns have been raised. Ozone therapy should not delay or replace assessment and treatment of conditions such as cancer, infected wounds or progressive nerve symptoms, and sudden weakness, speech change, chest pain or fever after a procedure needs urgent medical care.