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EBO2 (EBOO) research, annotated

Every peer-reviewed paper we have found on EBO2 (also called EBOO), the published reports of harm after ozone treatments, and the ozone-therapy literature clinics most often cite. For each one we record what kind of study it is, how many people were in it, what the authors reported, and what limits how much the result can tell you.

The short version: the studies of EBOO as given to people are few and small, date mostly from the early-to-mid 2000s, and come largely from the group that developed the technique. Laboratory and device-development work on the circuit is filed with the background science. No large, independent, randomized trial has been published. Read the complete guide for how this fits together.

We leave out conference abstracts, marketing white papers, and unpublished clinic data.

Figure 1. The 6 published papers on EBOO as given to people, one of them a review, by year. 4 appeared by 2010; the most recent is a case report from 2025. Select a block to jump to the study.

Studies of EBO2 / EBOO given to people

Reports of the procedure as given to patients, and a review of them by its developers. Laboratory and device-development work on the circuit is under background science.

Observed Reduction in Urinary Toxin Excretion With Extracorporeal Blood Oxygenation and Ozonation (EBOO) Treatment in an 88-Year-Old With Chronic Anemia: A Case Report

Bennett SJ, Kuo J, Wang S, et al. Cureus, 2025. PMID 41583215.

Case report, 1 person

88-year-old woman with chronic iron-deficiency anemia and environmental toxin burden

Our notes and where we cite it

Reported finding
Across two series of EBOO treatments, urinary toxin/creatinine ratios declined on average by 64.8% for mycotoxins, 25.7% for heavy metals, and 55.1% for other environmental toxins; nickel was the only toxin with an overall increase from baseline to the end of series II, and hemoglobin stayed largely unchanged.
Limitations
Single-patient case report with no control for ongoing environmental exposure between tests; it cannot establish causation or generalize beyond one patient. All four authors list New York practices (Hudson Health, Hudson Medical Group, Extension Health), and an Extension Health in New York is listed in this site's clinic directory as offering EBO2. The paper declares no conflicts of interest.

Ozone dialysis delivers three or more times the ozone than other forms of ozone blood treatment

Rowen RJ, Grabovac S, Su TB. Medical Gas Research, 2023. PMID 36204785.

Case series, 12 people

Our notes and where we cite it

Reported finding
In 85 measurements on 12 patients receiving ozone dialysis, the authors report an average uptake of 37% of the generator output (range 25-50%) and conclude uptake is at least 3 times higher than other blood-ozone methods, using theoretical delivery figures for those methods.
Limitations
Measurements from one clinic, reported by the technique's own practitioners, with no comparison group and no clinical outcomes; the figures for other methods are theoretical maximums, not measurements. PubMed lists no design type; we call it a case series.

Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy

Di Paolo N, Gaggiotti E, Galli F. Redox Report, 2005. PMID 16156950.

Review

Our notes and where we cite it

Reported finding
Describes EBOO as run on a high-efficiency apparatus that treats up to 4,800 ml of heparinized blood in 1 h with an oxygen-ozone mixture (0.5-1 microg/ml oxygen), against 250 ml by autohemotherapy, in a standard cycle of 14 one-hour sessions over 7 weeks. The authors report more than 1,200 treatments in 82 patients and state their experience confirms therapeutic potential.
Limitations
Narrative review from the Siena nephrology and dialysis department, the group behind the EBOO papers in this library. The abstract reports no controlled outcome data, and the clinical statements are the authors' own. Read from the abstract only.

Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease

Di Paolo N, Bocci V, Salvo DP, et al. International Journal of Artificial Organs, 2005. PMID 16288443.

Randomized controlled trial, 28 people

Patients with peripheral artery disease

Our notes and where we cite it

Reported finding
In 28 patients with peripheral artery disease randomized to EBOO or intravenous prostacyclin, the abstract reports highly significant regression of skin lesions with EBOO, and says pain, pruritus, heavy legs and well-being differed significantly between the two groups; it found no significant change in vascularisation of the lower limbs before and after treatment in either group.
Limitations
Small sample of 28 patients from a single Italian center; the available abstract does not describe blinding of outcome assessment or the randomization method.

Necrotizing fasciitis successfully treated with extracorporeal blood oxygenation and ozonization (EBOO)

Di Paolo N, Bocci V, Cappelletti F, et al. International Journal of Artificial Organs, 2002. PMID 12518965.

Case report, 1 person

Dialysis patient with necrotizing fasciitis unresponsive to standard therapy

Our notes and where we cite it

Reported finding
A dialysis patient with necrotizing fasciitis who had not improved with traditional therapies improved radically after treatment with EBOO, which the authors describe as already used routinely at their hospital.
Limitations
Single case report from the technique's own developers, read from a four-sentence abstract only. That abstract gives no outcome measure, follow-up, or procedure details such as the number of sessions or the ozone dose, and the case has no control patient.

Extracorporeal blood oxygenation and ozonation (EBOO) in man. preliminary report

Di Paolo N, Bocci V, Garosi G, et al. International Journal of Artificial Organs, 2000. PMID 10741810.

Case series

Early human recipients of EBOO, including patients with atherosclerotic vasculopathy

Our notes and where we cite it

Reported finding
In the first human use of the EBOO apparatus, an author who volunteered to test the system noted disappearance of two lipomas after six treatments; the device was then used in a patient with Madelung disease and several patients with atherosclerotic vasculopathy. The authors state the preliminary results show therapeutic effects and no side effects.
Limitations
Uncontrolled preliminary case series performed by the device's own inventors, including self-experimentation; no blinding, randomization, or precisely reported total sample size.

Safety and adverse events

Harms reported after ozone therapy, and studies of how ozone exposure affects health.

Effectiveness and Safety of Ozone Therapy in Humans: An Umbrella Review of Systematic Reviews with Meta-Analyses of Randomized Clinical Trials

Cacciatore S, Abbatecola G, Calvani R, Veronese N. Medical Sciences (Basel), 2026. PMID 42346828.

Systematic review / meta-analysis

Systematic reviews with meta-analyses of randomized trials comparing ozone therapy with non-active controls in any condition; seven were included, covering four indications

Our notes and where we cite it

Reported finding
Seven meta-analyses (from 1243 records) were included, covering periodontitis, COVID-19, diabetic foot ulcers, and third-molar surgery. Ozone therapy showed no consistent benefit over non-active controls. Safety was inconsistently reported; the one pooled safety analysis found no significant difference in adverse events (RR 2.27; 95% CI 0.48-10.79). Evidence certainty was low or very low.
Limitations
An umbrella review of published meta-analyses without individual patient data; only four indications had eligible reviews, and adverse events were pooled in one of them (three trials). The authors cite possible omission of recent trials, varied ozone routes and doses, and the limited quality of the included reviews: two of seven were rated high confidence on AMSTAR-2.

Oxygen-ozone autohaemotherapy in fibromyalgia: safety profile and adverse events. A scoping review

Casale R, Petrikonis K, Ahmadian A, Bazzichi L, et al. Clinical and Experimental Rheumatology, 2026. PMID 42328943.

Review

Published reports, mostly case reports, of adverse events after systemic oxygen-ozone autohaemotherapy in the last decade, largely from mixed clinical populations rather than fibromyalgia

Our notes and where we cite it

Reported finding
The search found mainly case reports of adverse events: haemolysis and renal failure with ozone above 60 μg/mL, hyperkalaemia, myocardial infarction and ischaemic events, cerebral gas embolism with patent foramen ovale, autonomic reactions to rapid reinfusion, anaphylaxis linked to equipment, and infections from protocol breaches. The authors state incidence cannot be reliably quantified.
Limitations
Scoping review, read from the abstract only. It draws mostly on case reports from mixed clinical populations, covers the last decade and systemic routes only, and the authors state that incidence cannot be reliably quantified given the absence of prospective registries and reliable denominator data.

Haemolysis Generated with the Use of Glass Bottles Instead of PVC, DEHP-Free Blood Collection Bags in the Oxygen-Ozone Therapy

Franzini M, Chirumbolo S, Valdenassi L. Maedica, 2025. PMID 40880716.

Other

No patients: modelling of haemolysis in blood collected for major autohaemotherapy in glass bottles versus DEHP-free PVC bags, drawing on 25 laboratory experiments

Our notes and where we cite it

Reported finding
The authors modelled haemolysis, methaemoglobin formation, and inflammation with differential equations, drawing on 25 laboratory experiments (12 DEHP-free PVC bags, 13 glass bottles) and the literature. They report faster red-cell rupture in glass (p = 0.03433) and a higher safety index with plastic bags, and conclude that glass bottles should be phased out of major autohaemotherapy.
Limitations
A self-described commentary based on modelling; no adverse events in patients are reported. The equations and tables appear only as images, the 25 experiments are not described in detail, and the text and a figure caption disagree on how the safety index changes with ozone dose. Two of the three authors are from SIOOT, and the products compared are named brands.

How Safe Are Oxygen-Ozone Therapy Procedures for Spine Disc Herniation? The SIOOT Protocols for Treating Spine Disorders

Franzini M, Chirumbolo S, Vaiano F, Valdenassi L, et al. Journal of Imaging, 2025. PMID 41440568.

Other

Seven studies of intramuscular or intradiscal oxygen-ozone for disc herniation, pooled in a meta-analysis, plus CT scans of one 49-year-old man after an intramuscular injection

Our notes and where we cite it

Reported finding
CT of one man showed gas in a lumbar disc minutes after a paravertebral intramuscular oxygen-ozone injection, which the authors attribute to diffusion. A meta-analysis of seven studies gave pain effect sizes of g = -1.55 (intramuscular) and 2.87 (intradiscal), and the authors put severe adverse events at 6.57 times as likely with intradiscal procedures (number needed to harm about 1180).
Limitations
Nine of the 13 authors are from SIOOT, whose intramuscular protocol the paper recommends. The imaging is one patient, and the intradiscal estimate comes from uncontrolled cohorts. The abstract's 120 patients conflicts with Table 1, the text gives intradiscal complication rates of 9.52% and about 0.1%, and the intramuscular rate behind the NNH was back-calculated from the 6.57 ratio.

Medical Ozone as a Therapeutic Option in Musculoskeletal Pain Control: A Critical Review of Clinical Trials Considering Safety and Quality Indicators for Procedures and Devices

de Araújo LT, da Silva PC, Masini M. Yale Journal of Biology and Medicine, 2024. PMID 39351322.

Review

27 clinical studies (pilot, randomized, and non-randomized trials) of medical ozone for musculoskeletal pain in adults, each with at least five participants

Our notes and where we cite it

Reported finding
From 249 records, 27 studies were included, most on low back pain. By the authors' grading, 77.8% of studies had no adverse events, 14.8% mild, 3.7% moderate, and 3.7% serious events, none involving death or disability. Ten studies did not name the ozone generator used. The authors conclude that medical ozone is safe and effective for musculoskeletal pain and call for longer, rigorous trials.
Limitations
A critical review that grades quality indicators but uses no formal risk-of-bias tool. Case reports, case series, and studies with fewer than five participants were excluded, and only Portuguese, Spanish, and English papers were searched. The abstract gives the no-adverse-event share as "77 (8%)" and the text 77.8%. One author works for an ozone-generator maker that paid for the illustrations.

Associations between particulate matter air pollutants and hospitalization risk for systemic lupus erythematosus: a time-series study from Xi'an, China

Pan Y, Fang Y, Chen Y, et al. Environmental Geochemistry and Health, 2023. PMID 36287357.

Other

Our notes and where we cite it

Reported finding
A time-series study in Xi'an, China linked fine and coarse particulate matter with increased hospital admissions for systemic lupus erythematosus, while finding no significant association between ambient ozone (O3) and SLE admissions.
Limitations
An ecological, population-level air-pollution study of ambient exposure, not any ozone therapy; cannot show what a controlled medical ozone exposure does in an individual patient.

Combining Ozonated Autohemotherapy with Pharmacological Therapy for Comorbid Insomnia and Myofascial Pain Syndrome: A Prospective Randomized Controlled Study

Shen W, Liu N, Ji Z, et al. Pain Research & Management, 2022. PMID 37214227.

Randomized controlled trial, 118 people

Patients with comorbid insomnia and myofascial pain syndrome

Our notes and where we cite it

Reported finding
No adverse complications were observed in either group of this randomized trial, in which 118 patients were randomized and 103 completed follow-up. Compared with the control group, the group given ozonated autohemotherapy with the same drugs had significantly improved sleep quality, pain, and negative mood at different time points.
Limitations
Single-center trial. Controls had blood drawn without ozone and a sham infusion, and only the operator giving the infusions knew each patient's group, but the authors state that double blinding was not used. Of 118 randomized, 103 (50 control, 53 ozone) completed follow-up and are the ones reported. Harms were checked against a list of possible complications, and follow-up ended at 6 months.

Ozone-induced encephalopathy: A novel iatrogenic entity

Haggiag S, Prosperini L, Stasolla A, Gerace C, et al. European Journal of Neurology, 2021. PMID 33657263.

Case series, 3 people

Three patients (men aged 59 and 27, a woman aged 56) with neurological symptoms immediately or 5 minutes after cervical or lumbar ozone therapy

Our notes and where we cite it

Reported finding
Three patients had neurological symptoms immediately or 5 minutes after cervical or lumbar ozone therapy, among them loss of consciousness, cortical blindness, visual impairment, and vertigo. Brain MRI was normal except a subtle cerebellar change on one follow-up scan; two had a patent foramen ovale. All recovered fully within 48 hours. The authors found eight more cases in the literature.
Limitations
Three cases, read from the abstract only. The authors describe the findings as suggestive of ozone-induced encephalopathy, a term they introduce, and state that it likely has a complex pathogenesis; the abstract gives no ozone doses or volumes and no follow-up beyond recovery within 48 hours.

Safety, pitfalls, and misunderstandings about the use of ozone therapy as a regenerative medicine tool. A narrative review

Re L, Noci JB, Gadelha Serra ME, Mollica P, et al. Journal of Biological Regulators and Homeostatic Agents, 2020. PMID 33176412.

Review

Published case reports of adverse reactions attributed to ozone therapy, discussed by technique of administration

Our notes and where we cite it

Reported finding
Discussing published case reports of adverse reactions attributed to ozone therapy, by technique of administration, the authors state that most safety issues are secondary to infections or traumatic reactions due to malpractice, and that the ozone molecule itself is commonly not responsible for severe reactions under the therapeutic modalities.
Limitations
Narrative review, read from the abstract only. The abstract states no search method, number of reports reviewed, or event counts, and gives no counted figures for its statement that the millions of patients treated worldwide over 40 years demonstrate the therapy's safety.

Intraforaminal ozone therapy and particular side effects: preliminary results and early warning

Vanni D, Galzio R, Kazakova A, Pantalone A, et al. Acta Neurochirurgica, 2016. PMID 26293228.

Case series, 186 people

186 patients (97 men, 89 women, mean age 59.8) having microsurgery for lumbar disc hernia or segmental stenosis; 23 had prior intraforaminal ozone, 28 intraforaminal steroids

Our notes and where we cite it

Reported finding
During lumbar microsurgery in 186 patients, surgeons found hard adhesions between soft tissues and bone, with the nerve root contracted and firmly adherent to the dural sac or disc fragments, only in the group previously given intraforaminal ozone (23 patients, treated elsewhere 12 to 24 months earlier). Patients with no injections or with intraforaminal steroids showed no such abnormalities.
Limitations
Surgical series reported as preliminary results, read from the abstract only. The abstract does not give the size of the no-injection group, how many of the 23 ozone-treated patients had adhesions, whether the surgeons knew each patient's treatment history, or the ozone concentration and volume used.

A metaanalysis of the effectiveness and safety of ozone treatments for herniated lumbar discs

Steppan J, Meaders T, Muto M, Murphy KJ. Journal of Vascular and Interventional Radiology, 2010. PMID 20188591.

Systematic review / meta-analysis

Almost 8,000 patients from multiple centers, aged 13 to 94 years with all types of disc herniation, treated with oxygen/ozone in 12 studies

Our notes and where we cite it

Reported finding
The likelihood of complications was 0.064% in random-effects meta-analyses of 12 studies of oxygen/ozone covering almost 8,000 patients. The mean improvement was 3.9 on the visual analog scale and 25.7 on the Oswestry Disability Index, and the likelihood of improvement on the modified MacNab scale was 79.7%. The authors conclude that pain and function outcomes are similar to surgical discectomy.
Limitations
Read from the abstract only. The pooled figures describe ozone-treated patients, and the abstract reports no pooled comparison with a control group. The 12 studies were weighted by a study quality score; the abstract does not say how many were randomized or how complications were defined and recorded.

A cluster of hepatitis C virus infections associated with ozone-enriched transfusion of autologous blood in Rome, Italy

Faustini A, Capobianchi MR, Martinelli M, Abbate I, et al. Infection Control and Hospital Epidemiology, 2005. PMID 16209382.

Cohort study, 31 people

All 42 patients exposed to ozone therapy by autohemotherapy or intramuscular injection at a hospital outpatient department in Rome, January to June 2001; 31 (74%) took part

Our notes and where we cite it

Reported finding
Of 31 participating patients, six were positive for HCV antibodies and HCV RNA, a prevalence of 19.4% against an estimated 0.9% in the population, and three (9.7%) had symptoms of HCV infection. One of the six had been known to be infected since 1986 and could have been the source. All infected patients had received ozone-enriched transfusions of autologous blood.
Limitations
Retrospective investigation of one outbreak at one outpatient department, read from the abstract only. Of the 42 exposed patients, 31 took part, and the authors state that the specific mode of transmission between patients was not detected.

Health effects of ozone. A critical review

Lippmann M. JAPCA (Journal of the Air Pollution Control Association), 1989. PMID 2659744.

Review

Our notes and where we cite it

Reported finding
A critical review of inhaled ambient ozone air pollution finding that peak levels common in US air cause measurable transient lung-function changes, respiratory symptoms, and airway inflammation, with animal data suggesting cumulative structural lung damage from repeated exposure.
Limitations
Covers inhaled ambient ozone air pollution, not any medical ozone therapy; describes breathing exposure, not the injected or blood-contact routes clinics use.

Ozone: a possible cause of hemolytic anemia in glucose-6-phosphate dehydrogenase deficient individuals

Calabrese EJ, Kojola WH, Carnow BW. Journal of Toxicology and Environmental Health, 1977. PMID 846014.

Other

Our notes and where we cite it

Reported finding
A theoretical model predicting that people with glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience acute hemolysis on exposure to ozone at levels reached in polluted urban air.
Limitations
A theoretical, computational model of inhaled ambient ozone, not an experiment on blood or on any ozone therapy procedure; does not test the brief controlled blood contact EBO2 or MAH use.
Show the 24 single case reportsHide the case reports

Each case report describes one patient, or a few. Together they show what has gone wrong after ozone treatment and how it was reported, not how often it happens.

Septic Arthritis of the Shoulder Following Ozone Therapy: A Case Report

Cortez F, Roncolato E, Machado M, Cubas V. Cureus, 2026. PMID 41728388.

Case report, 1 person

65-year-old man with HIV (low viral load), hypothyroidism, and hypertension, given a single ozone therapy session by a physical therapist for right shoulder pain

Our notes and where we cite it

Reported finding
After a single ozone therapy session with a physical therapist for two years of right shoulder pain, the patient worsened; 15 days later he had inflammatory signs, a 60 cm³ subcutaneous collection, and bone rarefaction of the clavicle and acromion. Debridement drained pus, and culture grew Staphylococcus aureus. After four weeks of oral antibiotics he had no pain at six weeks or six months.
Limitations
Single case report; the authors state that it does not establish a causal relationship and that patient comorbidities, including HIV, and procedural factors cannot be excluded. The ozone route, injection site, and dose are not reported.

Simultaneous pneumocephalus and meningitis as a complication of ozone therapy

Elmas Dal S. Northern Clinics of Istanbul, 2026. PMID 42516792.

Case report, 1 person

38-year-old man with ankylosing spondylitis, given ozone injections at a private clinic into the paravertebral back and lumbar regions and the front of the neck for pain

Our notes and where we cite it

Reported finding
A day after paravertebral ozone injections along the back and lumbar area and into the front of the neck at a private clinic, the patient had headache, fever, vomiting, confusion, and neck stiffness. CT showed air in the left lateral ventricle; cerebrospinal fluid held 4000 leukocytes/mm3, with negative cultures. On empirical antibiotics and dexamethasone the air was gone by day 14; he recovered.
Limitations
Single case report. Cerebrospinal fluid was sampled after antibiotics had begun, and no organism was identified. The author considers a contaminated needle that entered the subarachnoid space the likely cause; no ozone dose, volume, or needle depth is reported, and follow-up ended one week after discharge.

Hyperbaric Oxygen Treatment for Arterial Gas Embolism With Transient Cortical Blindness Following Intravenous Ozone Therapy: A Case Report

Singh S, Nevarez J. Undersea & Hyperbaric Medicine, 2026. PMID 42365944.

Case report, 1 person

64-year-old woman with sudden left leg weakness and loss of vision in both eyes after a session of intravenous ozone therapy

Our notes and where we cite it

Reported finding
After a session of intravenous ozone therapy, a 64-year-old woman had sudden left lower extremity weakness and bilateral vision loss. Initial imaging showed no acute abnormality, but her presentation was consistent with cerebral arterial gas embolism. After hyperbaric oxygen at 2.8 ATA and further sessions at 2.0 ATA, her visual and motor deficits resolved fully.
Limitations
Single case report, read from the abstract only. The gas embolism was a clinical diagnosis, since initial imaging showed no acute abnormality; the abstract gives no ozone dose or volume, no method of intravenous administration, and no number of hyperbaric sessions.

Spondylodiscitis Following Oxygen-Ozone Therapy: A Case Report of Lactobacillus iners Infection and a Systematic Literature Review

Velluto C, Mazzella GG, Inverso M, Borruto MI, et al. Diseases (Basel), 2026. PMID 41892016.

Case report, 1 person

Immunocompetent 55-year-old woman given five sessions of intradiscal oxygen-ozone for an L4-L5 disc herniation; the review covers published cases of spondylodiscitis after such therapy

Our notes and where we cite it

Reported finding
After five sessions of intradiscal oxygen-ozone in March 2022 for an L4-L5 herniation, pain worsened from July; CRP was 91 mg/L and MRI showed L4-L5 spondylodiscitis. Biopsy identified Lactobacillus iners, and she recovered fully after decompression and intravenous antibiotics. The review found eight earlier cases with varied pathogens; all but one, a death from septic shock, ended favorably.
Limitations
Single case; the authors state that a direct causal link cannot be proven. The review rests on a few case reports, its abstract gives both six included and eight identified cases, and the authors cite incomplete microbiological data and publication bias. The paper's conflict-of-interest section holds a consent sentence rather than a declaration.

Ozone-Induced Encephalopathy Following Subcutaneous Ozone Injection: A Case Report

Gante C, Dias L. Cureus, 2025. PMID 41492606.

Case report, 1 person

55-year-old man with no significant past medical history, given a subcutaneous ozone injection at facial acupuncture points as an alternative therapy for seasonal allergies

Our notes and where we cite it

Reported finding
About 10 minutes after a subcutaneous ozone injection at acupuncture points in the face, the patient developed confusion, ataxia, and involuntary limb movements and was intubated. CT was normal; MRI showed transient cortical diffusion abnormalities. Symptoms resolved without specific therapy after 48 hours of ventilation, and a repeat MRI 4 days later was normal.
Limitations
Single case report. The authors state that definitive causality cannot be established; the diagnosis of ozone-induced encephalopathy rests on timing and the exclusion of other causes. No ozone dose or volume is reported, and the patient did not attend the six-month follow-up.

Ozone therapy-associated pneumoperitoneum in a patient with low back pain: A case report

Shamohammadi M, Mazraeh M, Tayebi A, Olamaeian F, et al. International Journal of Surgery Case Reports, 2025. PMID 40233642.

Case report, 1 person

57-year-old woman with type 2 diabetes, hypertension, and ischemic heart disease, treated with ozone therapy for L4-L5 lumbar disc herniation

Our notes and where we cite it

Reported finding
Ten minutes after her second ozone therapy session for lumbar disc herniation the patient developed abdominal pain and distension. X-rays and CT showed free air in the peritoneum and retroperitoneum without free fluid, and blood tests showed no notable abnormalities. She was treated without surgery in intensive care, discharged after five days, and was asymptomatic at one month.
Limitations
Single case report. The authors state that the mechanism is undefined and suggest high-pressure ozone administration or improper instrument insertion. The route, site, ozone concentration, and volume of the session are not reported, and follow-up was one month.

Neurological Crisis Following Intravenous Ozone Therapy; a Case Report

Wong CYY, Saxena K, Meneer J, George K, et al. Archives of Academic Emergency Medicine, 2025. PMID 40027218.

Case report, 1 person

36-year-old woman with no significant medical history, given intravenous ozone therapy at a private outpatient session 'to boost her immunity'

Our notes and where we cite it

Reported finding
Minutes after an intravenous ozone session (autotransfusion of 150 mL of ozone-infused blood with heparin) the patient had chest pain, syncope, and a seizure. MRI showed multiple ischemic infarcts consistent with an embolic event, and echocardiography a small patent foramen ovale. She needed intubation and intensive care; at nine months she still had cognitive difficulties.
Limitations
Single case report: it shows the event followed this procedure, not how often it occurs. Cerebral air embolism was the suspected, not a confirmed, diagnosis, and no ozone concentration is reported. The authors cite delays in diagnosis, limited generalizability to other healthcare settings, and no follow-up beyond 9 months.

Cerebral gas embolism and multifocal ischemic stroke during oxygen-ozone therapy: a case report

Khosravi S, Mirzaasgari Z. BMJ Neurology Open, 2024. PMID 39720509.

Case report, 1 person

58-year-old woman with no known previous medical history, receiving a lumbar intradiscal oxygen-ozone injection for disc herniation pain

Our notes and where we cite it

Reported finding
During a lumbar intradiscal oxygen-ozone injection the patient developed speech disturbance and limb weakness; CT showed multiple cerebral gas bubbles and MRI showed acute infarcts in both hemispheres. Contrast echocardiography suggested a small patent foramen ovale. At 12 months she had no symptoms (Modified Rankin Scale 0).
Limitations
Single case report: it shows the event can occur during this procedure, not how often it occurs or who is at risk. No ozone concentration or injected gas volume is reported, and the authors note that how the gas reaches the arterial circulation is not fully understood.

Mycobacterium tuberculosis Infection of the Spine Secondary to Oxygen - Ozone Therapy for Prolapse Intervertebral Disc: A Scoping Review

Salaria AK, Dhatt SS, Kumar V, Neradi D, et al. Journal of Orthopaedic Case Reports, 2021. PMID 35437492.

Case report, 1 person

55-year-old woman, a farmer, given intradiscal ozone with a steroid at L3/L4 and L4/L5 for prolapsed intervertebral discs at another hospital

Our notes and where we cite it

Reported finding
After intradiscal instillation of 30% ozone (20 ml) with a steroid at L3/L4 and L4/L5, pain returned within 10 days. After 3 months of progressive symptoms she had fever, weight loss, and pre- and paravertebral and epidural collections reaching both psoas muscles, with aspiration cytology positive for acid-fast bacilli. On anti-tuberculosis treatment, MRI at 6 months showed partial healing.
Limitations
Single case report; the infection is linked to the injection by its history and timing. Tuberculosis was diagnosed from a positive acid-fast stain, and no culture result is reported. Although titled a scoping review, the paper describes no search method, and the patient was still under follow-up on treatment at the time of writing.

A Non-ST Elevation Myocardial Infarction Associated with Alternative Medicine Ozone Infusion

Bingham A, Platt M. Journal of Emergency Medicine, 2020. PMID 31708316.

Case report, 1 person

50-year-old white woman given an alternative-medicine ozone infusion: her blood drawn, ozone gas injected into it, and the blood transfused back intravenously

Our notes and where we cite it

Reported finding
After an ozone infusion (her blood drawn, ozone gas injected into it, and the blood transfused back intravenously), a 50-year-old woman had syncope. Her first electrocardiogram showed no infarction or ischemia, but troponin I was elevated and rising; she was admitted with a non-ST elevation myocardial infarction, which the authors associate with oxidative myocardial stress from ozone.
Limitations
Single case report, read from the abstract only. The abstract gives no ozone concentration, gas or blood volume, or findings of the cardiac evaluation, and it shows the event followed this procedure, not how often it occurs.

Mycobacterium abscessus mimicking tubercular spondylodiscitis following ozone therapy: A case report and review of literature

Shahi PB, Panigrahi V, Adsul N, Kumar M, et al. Surgical Neurology International, 2020. PMID 32363058.

Case report, 1 person

Healthy, non-immunocompromised 43-year-old woman given a fluoroscopically guided percutaneous ozone treatment for degenerative disc disease at L4-L5

Our notes and where we cite it

Reported finding
Three months after a fluoroscopically guided percutaneous ozone treatment at L4-L5, the patient had severe back pain, radiculopathy in both legs, a partial right foot drop, and raised CRP and ESR; MRI showed L4-L5 spondylodiscitis. Mycobacterium abscessus grew from epidural pus taken at fusion surgery. After a later wound debridement she was treated with amikacin and clarithromycin.
Limitations
Single case report; the infection is linked to the ozone treatment by its timing. The ozone dose, volume, and technique are not reported. The abstract and the case text describe the antibiotic course differently, and the case text gives no length of follow-up and no outcome beyond resolution of the primary infection.

Suspected Pulmonary Embolism after Oxygen-Ozone Therapy for Low Back Pain

Chirchiglia D, Chirchiglia P, Stroscio C, Volpentesta G, et al. Journal of Neurological Surgery Part A: Central European Neurosurgery, 2019. PMID 31430795.

Case report, 1 person

Elderly woman treated with oxygen-ozone therapy for lumbar pain caused by disk protrusion

Our notes and where we cite it

Reported finding
An elderly woman treated with oxygen-ozone therapy for lumbar pain from a disk protrusion had a suspected pulmonary embolism followed by sudden death. The authors believe a massive pulmonary embolism occurred, probably caused by an intradiskal injection that accidentally punctured a venous vessel and created emboli.
Limitations
Single case report, read from the abstract only. The embolism is described as suspected and its cause as the authors' belief; the abstract gives no age beyond "elderly", no ozone dose or volume, and no timing, and does not say how the diagnosis was investigated.

Multifocal Stroke From Ozone Gas Emboli

Freund PR, Alshafai L, Margolin EA. Journal of Neuro-Ophthalmology, 2019. PMID 30741783.

Case report, 1 person

34-year-old man with chronic neck pain treated with regular cervical paravertebral ozone injections

Our notes and where we cite it

Reported finding
After his last cervical paravertebral ozone injection, a 34-year-old man treated regularly with such injections for chronic neck pain had a syncopal episode and woke with ataxia, aphasia, hemiparesis, and a left sixth nerve palsy. CT angiography showed gas inside the right vertebral artery, and brain MRI showed multiple posterior circulation infarcts.
Limitations
Single case report, read from a four-sentence abstract only. The abstract gives no ozone dose or volume, number of injections, treatment of the stroke, or outcome, and it shows the event occurred, not how often it occurs.

A Case of Paradoxical Embolism Causing Anterior Spinal Cord Syndrome and Acute Myocardial Infarction Following the Intradiscal Oxygen-Ozone Therapy

He R, Huang Q, Yan X, Liu Y, et al. Frontiers in Neurology, 2019. PMID 30853936.

Case report, 1 person

66-year-old woman with lumbar disc herniation at L4/L5 and L5/S1, without hypertension or coronary heart disease, given an intradiscal oxygen-ozone injection

Our notes and where we cite it

Reported finding
During a CT-guided intradiscal oxygen-ozone injection, after 8 ml of gas, the patient developed flaccid paralysis of both legs, then chest pain with ST elevation; coronary angiography found no vascular abnormality. MRI showed a thoracic cord lesion from T2 to T10, and contrast echocardiography a large patent foramen ovale. At nine months she could stand with a cane.
Limitations
Single case report. The authors judge air embolism through a patent foramen ovale the most likely cause after excluding other causes; the gas itself was not imaged. No ozone concentration is reported, and the abstract and case text give different times for the onset of chest pain.

Cardiopulmonary Arrest and Pneumoencephaly Developing after Epidural Oxygen-ozone Mixture Therapy

Beyaz SG, Altaş C, Sayhan H. Anesthesia, Essays and Researches, 2018. PMID 29628600.

Case report, 1 person

79-year-old woman with hypertension, controlled diabetes, and asthma, given epidural oxygen-ozone through a Racz catheter for epidural lysis for low back pain

Our notes and where we cite it

Reported finding
On the second day of planned epidural oxygen-ozone injections through a Racz catheter, 20 mL (20 μg/mL) was injected instead of the planned 8 mL. Two minutes later the patient lost consciousness and had a cardiopulmonary arrest; sinus rhythm returned after 10 minutes of resuscitation. CT showed widespread intracranial air, which had resolved by day 7. She was extubated on day 4 and discharged.
Limitations
Single case report. The authors infer from the timing and the imaging that the mixture reached the cranium through the intrathecal route, possibly after the catheter injured the dura. The event followed an accidental injection of 20 mL instead of the planned 8 mL, and no follow-up after discharge is reported.

Ozone therapy induced sinus arrest in a hypertensive patient with chronic kidney disease: A case report

Tang WJ, Jiang L, Wang Y, et al. Medicine (Baltimore), 2017. PMID 29390373.

Case report, 1 person

54-year-old woman with hypertension, diabetes, and chronic kidney disease

Our notes and where we cite it

Reported finding
A patient using ozone autohemotherapy for hypertension and diabetes developed sudden dizziness from hyperkalemia that progressed to sinus arrest; the arrhythmia resolved after stopping ozone therapy and treating the hyperkalemia.
Limitations
Single case report; the association between ozone autohemotherapy and hyperkalemia-induced sinus arrest is based on temporal sequence, not confirmed mechanistic causation.

Cervical Spondylodiscitis After Oxygen-Ozone Therapy for Treatment of a Cervical Disc Herniation: a Case Report and Review of the Literature

Andrés-Cano P, Vela T, Cano C, García G, et al. HSS Journal, 2016. PMID 27703423.

Case report, 1 person

Previously healthy 51-year-old woman given C6-C7 intradiscal oxygen-ozone chemonucleolysis for a cervical disc herniation at an outside hospital

Our notes and where we cite it

Reported finding
Ten days after C6-C7 intradiscal oxygen-ozone chemonucleolysis, the patient had severe sepsis from C6-C7 spondylodiscitis, with an epidural abscess from C4 to T1 compressing the cord. Beta-hemolytic streptococcus grew, and the authors suspect a puncture through the esophagus. After drainage, laminectomies, and two fusions for kyphosis and non-union, she was satisfied at 1 year.
Limitations
Single case report from 2005. The route of contamination, a transesophageal puncture, is the authors' inference from the organism found, and the procedure details come from the patient's account; the ozone concentration and volume used at the outside hospital are not reported. The literature review is narrative, without a stated search method.

Transient cortical blindness after intradiscal oxygen-ozone therapy

Vaiano AS, Valente C, De Benedetti G, Caramello G. Indian Journal of Ophthalmology, 2016. PMID 28112142.

Case report, 1 person

54-year-old Caucasian man with lumbar sciatica and migraine, given an L5-S1 intradiscal and periganglionic oxygen-ozone injection for disc herniation

Our notes and where we cite it

Reported finding
About one minute after an L5-S1 oxygen-ozone injection (4 ml intradiscal and 11 ml periganglionic; ozone 27 μg/mL) the patient lost vision in both eyes, followed by headache and vomiting. MRI showed ischemic lesions in both posterior cerebral artery territories, and transesophageal echocardiography a large patent foramen ovale. Vision recovered fully by day 9 and was normal at 2 months.
Limitations
Single case report: it shows the event can follow this procedure, not how often it occurs. The authors consider air embolism through a patent foramen ovale the most likely cause but state that the pathophysiology remains elusive; the diagnosis rests on clinical findings and timing, and they also list an incidental stroke unrelated to the procedure as possible.

Myocardial Infarction after Ozone Therapy: Is Ozone Therapy Dr. Jekyll or Mr. Hyde?

Üreyen CM, Baş CY, Arslan Ş. Cardiology, 2015. PMID 26139204.

Case report, 1 person

46-year-old man without traditional atherosclerotic risk factors, given ozonated autohemotherapy at a private clinic the morning he presented

Our notes and where we cite it

Reported finding
A 46-year-old man without traditional atherosclerotic risk factors presented with acute inferior myocardial infarction after ozonated autohemotherapy at a private clinic that morning. Angiography showed vasospasm of the left main and proximal left anterior descending arteries, which resolved after nitrate, and a thrombotic total occlusion of the right coronary artery, which was stented.
Limitations
Single case report, read from the abstract only. The authors present ozone as a possible cause, supported by timing and the literature they refer to; the abstract gives no ozone dose, blood volume, or follow-up, and it shows the event occurred, not how often it occurs.

Pitfalls of Intralesional Ozone Injection in Diabetic Foot Ulcers: A Case Study

Uzun G, Mutluoğlu M, Karagöz H, Memiş A, et al. Journal of the American College of Clinical Wound Specialists, 2012. PMID 26199878.

Case report, 1 person

67-year-old woman with type 2 diabetes for 22 years and a 1 x 2 cm toe ulcer, treated at an ozone therapy center with topical ozone, major autohemotherapy, and intralesional injections

Our notes and where we cite it

Reported finding
After a week of topical ozone and major autohemotherapy failed, a physician at an ozone therapy center injected ozone into a 1 x 2 cm toe ulcer. After the second daily injection redness spread to the sole, and within two days the forefoot was necrotic. Healing took debridement, intravenous antibiotics, hyperbaric oxygen, a failed skin graft with fourth-toe amputation, and a great-toe fillet flap.
Limitations
Single case report. The ozone concentration and volume of the injections are not reported. The ulcer already had surrounding erythema and swelling before the ozone treatments, and glycemic control was poor on admission (HbA1c 11%). The last reported follow-up was at two months.

Fulminating septicemia secondary to oxygen-ozone therapy for lumbar disc herniation: case report

Gazzeri R, Galarza M, Neroni M, Esposito S, et al. Spine, 2007. PMID 17268255.

Case report, 1 person

57-year-old man previously treated with oxygen-ozone therapy, presenting with low back and bilateral pain and L4-L5 and L5-S1 disc herniations on CT

Our notes and where we cite it

Reported finding
Three days after admission to hospital, a 57-year-old man previously treated with oxygen-ozone therapy for lumbar disc herniation developed fulminant septicemia. CT and blood culture showed pyogenic involvement of the lumbar muscles with septic pulmonary embolism from Escherichia coli infection. The authors describe the complication as fatal.
Limitations
Single case report, read from the abstract only. The abstract does not state the route, number, or timing of the oxygen-ozone treatments, the ozone dose, or how and when the patient died, and it shows the event occurred, not how often it occurs.

A case of vertebrobasilar stroke during oxygen-ozone therapy

Corea F, Amici S, Murgia N, Tambasco N. Journal of Stroke and Cerebrovascular Diseases, 2004. PMID 17903984.

Case report, 1 person

Patient who had a vertebrobasilar stroke during medical oxygen-ozone therapy, discussed in the abstract as a treatment for lumbar disk herniation; no age or sex given

Our notes and where we cite it

Reported finding
The authors report what they describe as the first case of stroke during medical oxygen-ozone therapy, which the abstract discusses as combined intradiscal and periganglionic injection for lumbar disk herniation. The patient had Anton's syndrome as a result of hypoperfusion at the top of the basilar artery.
Limitations
Single case report, read from a four-sentence abstract only. The abstract does not state the patient's age or sex, the injection route or ozone dose, the timing of the stroke, or the outcome.

Acute bilateral vitreo-retinal hemorrhages following oxygen-ozone therapy for lumbar disk herniation

Lo Giudice G, Valdi F, Gismondi M, Prosdocimo G, et al. American Journal of Ophthalmology, 2004. PMID 15234314.

Case report, 1 person

45-year-old woman with acute bilateral visual loss after intradiscal and periganglionic injection of an oxygen-ozone mixture for lumbar disk herniation

Our notes and where we cite it

Reported finding
After intradiscal and periganglionic injection of an oxygen-ozone mixture for lumbar disk herniation, a 45-year-old woman had acute visual loss in both eyes: a premacular hemorrhage involving the left macula and multiple flat retinal hemorrhages in the right eye. MRI showed no intracranial hemorrhage; the left premacular hemorrhage was drained with Nd:YAG laser a few weeks later.
Limitations
Single case report, read from the abstract only. The abstract gives no ozone concentration or volume, no visual acuity before or after treatment, and no length of follow-up, and it shows the event occurred, not how often it occurs.

An unexpected death during oxygen-ozone therapy

Marchetti D, La Monaca G. American Journal of Forensic Medicine and Pathology, 2000. PMID 10871129.

Case report, 1 person

Patient given oxygen-ozone therapy by autohemotransfusion for psoriasis; the abstract gives no age or sex

Our notes and where we cite it

Reported finding
The authors describe an unexpected death caused by gas embolism that occurred during oxygen-ozone therapy administered by autohemotransfusion for psoriasis, and state that this complication suggests the need to investigate the benefits and adverse effects of medical ozone application.
Limitations
Single case report, read from a two-sentence abstract only: the abstract gives no patient details, ozone dose, blood volume, or account of how the gas embolism was identified. It shows the event occurred, not how often it occurs.

Ozone therapy more broadly

Other ozone methods, such as major autohemotherapy, that clinics cite in support of EBO2. A result for one method does not transfer automatically to another.

Show all 16 studiesHide these studies

Efficacy of major ozone autohemotherapy in patients with post-COVID syndrome

Kuculmez O. Frontiers in Medicine, 2026. PMID 41767530.

Case series, 40 people

Patients diagnosed with post-COVID syndrome

Our notes and where we cite it

Reported finding
A retrospective review of 40 patients given 10 sessions of major ozone autohemotherapy for post-COVID syndrome found statistically significant improvement in anxiety, depression, fatigue, and quality-of-life scores after treatment.
Limitations
Retrospective single-center chart review with no control group and no blinding; a before-after comparison cannot rule out natural recovery or other concurrent care.

SIOOT recommendations for the optimal application of the oxygen-ozone therapy in clinical medicine

Franzini M, Vaiano F, Tirelli U, et al. International Immunopharmacology, 2025. PMID 39657536.

Other

Our notes and where we cite it

Reported finding
A professional-society position paper arguing that oxygen-ozone therapy needs standardized protocols and physician training, stating that inconsistent practice currently limits safety, efficacy, and reproducibility across the field.
Limitations
A recommendations and position statement from an ozone-therapy society (SIOOT), not a controlled study; reports no new patient outcomes or trial data of its own.

A pilot randomized controlled trial of major ozone autohemotherapy for patients with post-acute sequelae of COVID-19

He Y, Liu X, Zha S, et al. International Immunopharmacology, 2024. PMID 39018686.

Randomized controlled trial, 73 people

Patients with post-acute sequelae of COVID-19

Our notes and where we cite it

Reported finding
In a pilot RCT, 35 patients given major ozone autohemotherapy plus conventional therapy had a higher symptom-score response rate (71%) than 38 given conventional therapy alone (45%), with better walk distance and lung function measures.
Limitations
The authors describe it as a pilot needing validation; tests major autohemotherapy, not EBO2, and the abstract does not describe blinding of outcome assessment.

Intra-articular injections of ozone versus hyaluronic acid for knee osteoarthritis: a level I meta-analysis

Migliorini F, Giorgino R, Mazzoleni MG, et al. European Journal of Orthopaedic Surgery & Traumatology, 2024. PMID 39579218.

Systematic review / meta-analysis, 424 people, pooled from the included trials

Patients with knee osteoarthritis, pooled from randomized trials comparing ozone with hyaluronic acid

Our notes and where we cite it

Reported finding
A level-I meta-analysis pooling 424 patients from randomized trials found intra-articular ozone injections produced pain scores (visual analogue scale) statistically similar to hyaluronic acid injections at 4-6 months follow-up.
Limitations
Restricted to studies with 4-6 month follow-up, so longer-term comparative efficacy is unknown; only ozone-versus-hyaluronic-acid comparisons were analyzed, with no placebo arm.

Clinical effectiveness of medical ozone therapy in COVID-19: the evidence and gaps map

Serra MEG, Baeza-Noci J, Abdala CVM, et al. Medical Gas Research, 2023. PMID 37077114.

Review, 271 people, across the studies it reviews

Patients across 13 pooled clinical studies of medical ozone therapy in COVID-19

Our notes and where we cite it

Reported finding
An evidence-and-gaps map of 13 clinical studies (271 patients total) on medical ozone therapy for COVID-19, mostly major or minor autohemotherapy or rectal insufflation in acute, often hospitalized infection.
Limitations
Authored by ozone-therapy society members; maps existing acute-COVID studies rather than long COVID, and includes no EBO2-specific study.

Sjögren syndrome successfully treated with oxygen-ozone auto-hemotherapy (O2-O3-AHT). A case report

Valdenassi L, Rossi E, Corsetti MT, et al. European Review for Medical and Pharmacological Sciences, 2022. PMID 36066166.

Case report, 1 person

69-year-old woman with primary Sjögren syndrome

Our notes and where we cite it

Reported finding
A 69-year-old woman with primary Sjögren syndrome was given two series of three weekly oxygen-ozone autohemotherapy sessions; the authors report that she improved after two sessions and that her ocular dryness, fatigue, and pain rapidly disappeared.
Limitations
One patient, no control group, and no blinding; cannot separate any ozone effect from the natural course of the disease or other concurrent care. The first and last authors list the Italian Society of Oxygen-Ozone Therapy (SIOOT), four authors a university master's course in oxygen-ozone therapy, and the paper thanks SIOOT staff for technical support.

A systematic review of ozone therapy for treating chronically refractory wounds and ulcers

Wen Q, Liu D, Wang X, et al. International Wound Journal, 2022. PMID 34612569.

Systematic review / meta-analysis

People with chronic wounds and ulcers, mainly diabetic foot ulcers, pooled from 12 randomized trials

Our notes and where we cite it

Reported finding
Pooling 12 randomized trials of topical or systemic ozone therapy for chronic wounds, this review found ozone accelerated wound-area improvement and reduced amputation rate for diabetic foot ulcers versus standard care, though complete wound healing rates and hospital stay did not differ, with no reported adverse events attributed to ozone across included studies.
Limitations
Included trials varied widely in ozone delivery method and wound type; the authors state evidence for wound types other than diabetic foot ulcers remains uncertain due to insufficient studies.

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy, preliminary results on 100 patients

Tirelli U, Franzini M, Valdenassi L, et al. European Review for Medical and Pharmacological Sciences, 2021. PMID 34604980.

Case series, 100 people

Patients with post-COVID fatigue

Our notes and where we cite it

Reported finding
In 100 patients with post-COVID fatigue, a preliminary, uncontrolled series of oxygen-ozone autohemotherapy reported reduced fatigue scores after treatment.
Limitations
No comparison group, so how much of the change would have occurred anyway cannot be determined; preliminary results from ozone-therapy society-affiliated authors.

Ozone and oxidation therapies as a solution to the emerging crisis in infectious disease management: a review of current knowledge and experience

Rowen RJ. Medical Gas Research, 2019. PMID 31898609.

Review

Our notes and where we cite it

Reported finding
A narrative review arguing ozone therapy could serve as an adjunctive or stand-alone treatment for drug-resistant infections and outbreaks such as Ebola, describing it as having a strong safety record.
Limitations
A single author's advocacy-oriented narrative review with no systematic search or new controlled data, and no study of ozone against Borrelia or Lyme disease specifically.

Therapeutic Effect of Medical Ozone on Lumbar Disc Herniation

Niu T, Lv C, Yi G, et al. Medical Science Monitor, 2018. PMID 29611536.

Randomized controlled trial, 80 people

Patients with trauma-induced lumbar disc herniation

Our notes and where we cite it

Reported finding
In 80 patients randomized to control or low, medium (40 ug/mL), or high (60 ug/mL) concentrations of medical ozone, the medium concentration produced the greatest disc retraction and reduced inflammatory markers, while the highest concentration increased inflammatory marker expression instead of reducing it.
Limitations
Single-center trial; the abstract does not describe blinding; biochemical and imaging surrogate endpoints are emphasized alongside clinical pain scores.

Ozone therapy for treating foot ulcers in people with diabetes

Liu J, Zhang P, Tian J, et al. Cochrane Database of Systematic Reviews, 2015. PMID 26505864.

Systematic review / meta-analysis, 212 people, pooled from the included trials

People with diabetic foot ulcers, pooled from 3 randomized controlled trials

Our notes and where we cite it

Reported finding
This Cochrane review pooled 3 small randomized trials (212 participants): one found greater ulcer-area reduction and shorter hospitalization with ozone versus antibiotics, but pooled analysis of the other two found no significant difference from usual care in ulcer healing, adverse events, or amputation rate.
Limitations
Only three included trials, all judged at high or unclear risk of bias; the review authors conclude they are unable to draw any firm conclusions about effectiveness.

Sports massage with ozonised oil or non-ozonised oil: comparative effects on recovery parameters after maximal effort in cyclists

Paoli A, Bianco A, Battaglia G, et al. Physical Therapy in Sport, 2013. PMID 23623301.

Controlled trial (non-randomized), 15 people

Competitive amateur male cyclists

Our notes and where we cite it

Reported finding
In a within-subject comparison of 15 cyclists, sports massage with ozonised oil produced higher peak power and lower perceived fatigue after fatiguing exercise than massage without ozone or passive rest.
Limitations
Topical ozonised massage oil, not autohemotherapy or EBO2; a small single-center sample measuring short-term performance rather than any clinical outcome.

Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study

Borrelli E, Diadori A, Zalaffi A, et al. International Journal of Ophthalmology, 2012. PMID 23275905.

Randomized controlled trial, 140 people

Patients with dry age-related macular degeneration

Our notes and where we cite it

Reported finding
An open randomized trial of 140 patients compared 27 major ozonated autohemotherapy sessions over 12 months with multivitamins. The primary outcome, mean logMAR acuity change, did not differ significantly between groups (Table 3a). The abstract reports no acuity loss in treated eyes against 16% and 40% of controls losing 2 or more lines at 6 and 12 months, and higher plasma antioxidant potential.
Limitations
An open trial: by the authors' own description, neither the patients nor the investigator were blinded. The paper's Table 3a marks every comparison of the primary logMAR outcome as not significant, which the abstract does not mention; the line-loss percentages in the abstract are a secondary outcome. The senior author, Velio Bocci, was a leading proponent of ozone therapy.

Ozone therapy as a treatment for low back pain secondary to herniated disc: a systematic review and meta-analysis of randomized controlled trials

Magalhaes FN, Dotta L, Sasse A, et al. Pain Physician, 2012. PMID 22430658.

Systematic review / meta-analysis

Patients with chronic low back pain secondary to herniated disc

Our notes and where we cite it

Reported finding
A systematic review of 8 observational studies and meta-analysis of 4 randomized trials found percutaneous ozone injection (intradiscal or paravertebral) associated with positive pain outcomes and low morbidity, graded as evidence level II-1 to II-3 depending on route of injection.
Limitations
The authors themselves note a lack of precise diagnostic criteria and frequent use of mixed therapeutic agents across studies, that included trials were mainly active-control, and that no placebo-controlled trial was found.

Ozone therapy: a clinical review

Elvis AM, Ekta JS. Journal of Natural Science, Biology, and Medicine, 2011. PMID 22470237.

Review

Our notes and where we cite it

Reported finding
A general clinical review describing ozone's history, proposed mechanisms (antimicrobial action, immune stimulation), application methods, and the diseases it says ozone treats, from infected wounds and circulatory disorders to cancer, SARS, and AIDS.
Limitations
A broad narrative review without a systematic search or a stated evidence grade for the conditions it lists; does not address EBO2 specifically.

Plasmapheresis combined with cell mass ozonation in endogenous uveitis treatment

Onishchenko AL, Kolbasko AV, Chernysheva AD, et al. Vestnik Oftalmologii, 2011. PMID 22442992.

Other

179 patients (209 eyes) with endogenous uveitis, analyzed in 3 patient groups

Our notes and where we cite it

Reported finding
Analyzing treatment results in 3 patient groups (179 patients, 209 eyes) with endogenous uveitis, the authors report an advantage for their modification of plasmapheresis combined with ozonation of the cell mass, and describe effects such as correction of T-cell immunodeficiency and a decrease of circulating immune complexes. The abstract gives no figures.
Limitations
Abstract only (PubMed lists an English abstract for a non-English article). The abstract does not say how patients were assigned to the 3 groups, what the comparison groups received, the ozone dose, the follow-up, or any numeric result. Not the EBOO procedure: ozone is applied to the cell mass during plasmapheresis.

Background science and mechanism studies

How ozone acts on blood and cells, how blood filters work, the laboratory and device-development studies behind the EBOO circuit, and studies that measure markers in the blood rather than how patients fare. None of these shows whether EBO2 helps patients.

Show all 18 studiesHide these studies

Dialysis membranes and hemodialyzers

Clark WR, Lorenzin A, Ronco C. Contributions to Nephrology, 2026. PMID 42721103.

Review

Our notes and where we cite it

Reported finding
A nephrology review of how hollow-fiber hemodialysis membranes are classified by pore size and permeability, and how pore size determines which molecules a filter can remove by convection.
Limitations
Describes dialysis and hemodiafiltration membranes generally, not any EBO2 device specifically, and includes no ozone-related content.

Immunomodulation by extracorporeal ozone-based bactericide system in porcine Pseudomonas aeruginosa septic shock

Rundgren H, Sjöholm J, Juric S, et al. Scientific Reports, 2025. PMID 40562794.

Animal study, 13 animals

13 swine with P. aeruginosa septic shock, allocated to extracorporeal ozone treatment (7) or no ozone treatment (6)

Our notes and where we cite it

Reported finding
In pigs with P. aeruginosa septic shock (7 ozone, 6 none), one pass through the system cut viable bacteria by 53%, but bacteria in peripheral blood and survival (median 134 vs 159 min) did not differ. IL-1β, IL-4, IL-6, IL-8 and IFN-γ fell with ozonation, complement did not; hemoglobin, hematocrit, noradrenaline doses, breathing rate and peak airway pressure were lower with ozone.
Limitations
Not the EBOO procedure: a prototype that cools blood and mixes it with oxygen-ozone gas, at about 50 mL/min (about 2 L over 4 hours), in pigs. Small 4-hour feasibility study; groups were allocated, not stated as randomized, and with no ozone-free control circuit ozone is not separated from cooling or circuit effects. Funded by Sangair; two authors own or work for Sangair.

Advances in ozone technology for preservation of grains and end products: application techniques, control of microbial contaminants, mitigation of mycotoxins, impact on quality, and regulatory approvals

Sitoe EDPE, Pacheco FC, Chilala FD. Comprehensive Reviews in Food Science and Food Safety, 2025. PMID 40260769.

Review

Our notes and where we cite it

Reported finding
A food-science review of how gaseous ozone controls microbes and mycotoxins in stored grain, describing ozone's biocidal mechanism and regulatory approvals for food preservation.
Limitations
Entirely about industrial food and grain preservation, not human medicine or blood therapy; provides no evidence about mycotoxin removal from blood by EBO2 or any ozone therapy.

Lipoprotein apheresis: utility, outcomes, and implementation in clinical practice: a scientific statement from the American Heart Association

Gianos E, Duell PB, Toth PP, et al. Arteriosclerosis, Thrombosis, and Vascular Biology, 2024. PMID 39370995.

Review

Our notes and where we cite it

Reported finding
An American Heart Association scientific statement on lipoprotein apheresis, an extracorporeal procedure with FDA-approved indications that the authors call a valuable but underused option for lowering LDL cholesterol and lipoprotein(a), reviewing its history, mechanisms, outcomes, and indications.
Limitations
Reviews an established, evidence-graded procedure for cholesterol removal; does not evaluate EBO2 or claim that EBO2's filter achieves comparable, measured lipid removal.

Ozone high dose therapy (OHT) improves mitochondrial bioenergetics in peripheral blood mononuclear cells

König B, Lahodny J. Translational Medicine Communications, 2022. PMID 35880042.

Case series, 6 people

Our notes and where we cite it

Reported finding
In 6 patients given two 10-pass ozone high-dose therapy (OHT) sessions within a week, a laboratory bioenergetic health index in blood cells improved, driven mainly by increased mitochondrial reserve capacity.
Limitations
Six patients, no control group; a laboratory biomarker rather than a symptom or clinical outcome, co-authored by the technique's own developer. The abstract does not state a specific cumulative ozone dose in micrograms.

Evaluation of an extracorporeal ozone-based bactericide system for the treatment of Escherichia coli sepsis

Skorup P, Fransson A, Gustavsson J, et al. Intensive Care Medicine Experimental, 2022. PMID 35467176.

Animal study, 10 animals

10 swine with E. coli sepsis (5 randomized to ozone, 5 to none), plus 6 single-pass runs of E. coli-infected human whole blood

Our notes and where we cite it

Reported finding
One pass of E. coli-infected human whole blood through the extracorporeal ozonation prototype lowered viable E. coli by 27% (6 runs). In randomized septic swine (5 ozone, 5 none), 30 minutes of treatment did not change circulatory, respiratory or metabolic measures, bacteria in blood or organs, hemoglobin, leucocytes or methemoglobin; one ozone-group pig died before treatment began.
Limitations
Not the EBOO procedure: a prototype that cools blood and mixes it with oxygen-ozone gas, run for 30 minutes in a 3.5-hour pig sepsis model. Small feasibility study; the in vitro runs had no ozone-free control, and the authors call the model likely too short to detect improvement. Funded by an unrestricted Sangair AB grant; two authors own or work for Sangair.

Oxidative stress, antioxidants, hormesis and calorie restriction: the current perspective in the biology of aging

Mehdi MM, Solanki P, Singh P. Archives of Gerontology and Geriatrics, 2021. PMID 33845417.

Review

Our notes and where we cite it

Reported finding
A narrative review of how oxidative stress, antioxidant defenses, and hormesis (a low-dose stress producing a protective response) are theorized to shape biological aging.
Limitations
A general biology-of-aging review with no mention of ozone or EBO2; describes hormesis as a broad concept, not evidence that any ozone procedure slows aging.

The effects of oxygen-ozone therapy on regulatory T-cell responses in multiple sclerosis patients

Tahmasebi S, Qasim MT, Krivenkova MV, et al. Cell Biology International, 2021. PMID 33724614.

Case series, 20 people

Relapsing-remitting multiple sclerosis patients

Our notes and where we cite it

Reported finding
In 20 relapsing-remitting MS patients treated with ozone autohemotherapy twice weekly for 6 months, regulatory T-cell frequency and related anti-inflammatory markers (FoxP3, IL-10, TGF-beta) rose after treatment compared with before.
Limitations
Single-arm before-after design with no untreated control group and no blinding; measures a laboratory immune marker, not a clinical disability or symptom outcome.

Changes in Th17 cells frequency and function after ozone therapy used to treat multiple sclerosis patients

Izadi M, Tahmasebi S, Pustokhina I, et al. Multiple Sclerosis and Related Disorders, 2020. PMID 32862036.

Case series, 20 people

Multiple sclerosis patients

Our notes and where we cite it

Reported finding
In 20 MS patients, the authors' own "non-controlled study" found ozone autohemotherapy lowered the frequency of pro-inflammatory Th17 cells and related markers after treatment compared with before.
Limitations
The authors describe it as non-controlled; a before-after comparison in one treated group measuring a laboratory immune marker rather than disability or symptom outcomes.

Ozone: a natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders

Scassellati C, Galoforo AC, Bonvicini C, et al. Ageing Research Reviews, 2020. PMID 32810649.

Review

Our notes and where we cite it

Reported finding
A review arguing that ozone, through the Nrf2 antioxidant system, could be a new strategy in aging and to delay neurodegeneration. Through what it calls a meta-analytic approach, it reports significant modulation by ozone of endogenous antioxidant-Nrf2 (OR 1.71) and vitagene-Nrf2 (OR 1.80) systems.
Limitations
A hypothesis-generating review, not a clinical trial. Its pooled odds ratios combine before-and-after marker levels, from human studies for the antioxidant markers and from human, animal, and cell samples for the vitagene markers, with high heterogeneity (I² 97% and 66%); no human outcome links ozone to slower aging. One of its two co-first authors lists the ozone-therapy society SIOOT.

Effects of ozonated autohemotherapy on the antioxidant capacity of Thoroughbred horses

Tsuzuki N, Endo Y, Kikkawa L, et al. Journal of Veterinary Medical Science, 2016. PMID 26166812.

Animal study, 10 animals

Ten gelding Thoroughbred horses (non-race horses)

Our notes and where we cite it

Reported finding
In 10 non-race Thoroughbred geldings, each used as its own control, ozonated autohemotherapy was followed by a higher biological antioxidant potential at 3 and 7 days and a lower oxidative stress index; the reactive-oxygen-metabolite marker did not differ, and the antioxidant change was no longer measurable at 14 days.
Limitations
Animal study in ten horses, not humans; each horse served as its own control; measures blood antioxidant markers rather than any disease outcome, and does not test EBO2's continuous-filtration circuit.

Are dialysis devices usable as ozone gas exchangers?

Travagli V, Zanardi I, Gabbrielli A, et al. Artificial Organs, 2010. PMID 19817737.

In vitro

Four hydrophilic dialysis filters and one hydrophobic gas-exchange device, compared for ozone transfer

Our notes and where we cite it

Reported finding
Comparing ozone transfer in four hydrophilic dialysis filters and one hydrophobic gas-exchange device, the authors report filter yields from 0 to 70%, often varying with treatment time, and filter fibers somewhat altered by ozone under scanning microscopy. They state the filters may release toxic compounds, while the gas-exchange device was efficient and ozone-resistant.
Limitations
Bench comparison of devices, not the EBOO procedure as given to patients, and no clinical outcomes. The abstract names neither the filters nor the fluid tested, and the release of toxic compounds is stated as a possibility, not a measurement. Abstract only.

The ozone paradox: ozone is a strong oxidant as well as a medical drug

Bocci V, Borrelli E, Travagli V, et al. Medicinal Research Reviews, 2009. PMID 19260079.

Review

Our notes and where we cite it

Reported finding
Explains that prolonged ozone inhalation is toxic to the lungs and body, whereas a single, precisely calibrated ozone dose dissolved in blood ex vivo triggers antioxidant and biochemical responses in blood cells and endothelium that the authors describe as therapeutically useful without toxicity in selected diseases.
Limitations
Narrative review by long-time ozone-therapy proponents that synthesizes prior mechanistic work rather than presenting new controlled data.

Oxygenation-ozonation of blood during extracorporeal circulation: in vitro efficiency of a new gas exchange device

Bocci V, Zanardi I, Travagli V, et al. Artificial Organs, 2007. PMID 17725702.

In vitro

Our notes and where we cite it

Reported finding
Bench testing of a new hollow-fiber gas exchange device (L001) for EBOO, using a buffered saline solution containing KI rather than blood, showed efficient gas transfer with minimal foreign surface contact and negligible priming volume across the tested parameters.
Limitations
In vitro test on a saline solution, not blood or patients, with no clinical outcomes; PubMed lists no study-design publication type, so "in vitro" is inferred from the described bench methodology; authored by the EBOO technique's developers.

Ozone as Janus: this controversial gas can be either toxic or medically useful

Bocci V. Mediators of Inflammation, 2004. PMID 15203558.

Review

Our notes and where we cite it

Reported finding
Argues that ozone, though intrinsically toxic as an inhaled gas, produces a cascade of ozone-derived compounds when dissolved in blood at judicious, physician-controlled doses, yielding multifactorial beneficial effects in infections, vasculopathies, and orthopedic and dental conditions.
Limitations
Single-author narrative review without a systematic search methodology or quantitative synthesis of the underlying evidence.

No effects of ozonated autohemotherapy on inflammation response in hemodialyzed patients

Tylicki L, Biedunkiewicz B, Rachon D, et al. Mediators of Inflammation, 2004. PMID 15770057.

Controlled trial (non-randomized), 12 people

Chronically hemodialyzed patients with peripheral arterial disease

Our notes and where we cite it

Reported finding
In a controlled, single-blind, cross-over study of 12 hemodialysis patients, nine sessions of ozonated autohemotherapy produced no significant change in plasma C-reactive protein or interleukin-6 compared with nine sham (oxygen-only) autohemotherapy sessions.
Limitations
Small sample of 12 patients in a single crossover study; a null result for these two inflammatory markers does not rule out other biological effects of ozone.

Ozonation of blood during extracorporeal circulation. II. Comparative analysis of several oxygenator-ozonators and selection of one type

Bocci V, Di Paolo N, Borrelli E, et al. International Journal of Artificial Organs, 2001. PMID 11831595.

In vitro

Human blood exposed ex vivo to oxygen-ozone in dialysis exchangers, oxygenators, and hydrophobic hollow-fiber devices

Our notes and where we cite it

Reported finding
Comparing devices for exposing human blood to oxygen-ozone ex vivo, the authors found dialysis membranes unsuitable (all but one gas-transfer inefficient, allowing ultrafiltration, ozone-vulnerable) and improperly coated polypropylene fibers prone to platelet aggregation and clotting, prohibitive with ozone. Newer biocompatible oxygenators could treat up to 5 L of blood in about an hour.
Limitations
Bench comparison of devices with human blood ex vivo, not the EBOO procedure as given to patients, and no clinical outcomes. The abstract names neither the devices compared nor the one selected, and gives no numeric results. Abstract only.

Ozonation of blood during extracorporeal circulation. I. Rationale, methodology and preliminary studies

Bocci V, Di Paolo N, Garosi G, et al. International Journal of Artificial Organs, 1999. PMID 10532435.

Animal study

Saline and swine blood circulated through an oxygen-ozone gas exchanger in vitro, then sheep given extracorporeal circulation

Our notes and where we cite it

Reported finding
Dialysis-type membranes proved unsuitable for exposing blood to oxygen-ozone, so the authors used hydrophobic ozone-resistant hollow fibers. In saline, swine-blood and sheep tests they report that 10 µg/mL ozone produced biochemical effects, heparin was not an ideal anticoagulant, and sheep had no adverse effects after 50 min at 20 to 40 µg/mL, though the exchanger clogged with cells.
Limitations
Bench and sheep development work on an extracorporeal gas-exchanger circuit, not the EBOO procedure as given to patients, and no clinical outcomes. The abstract does not say how many sheep were studied, describes no control group, and gives no numeric biochemical results. Abstract only.