Cohort study · n = 40
Kuculmez O. Frontiers in Medicine, 2026. PMID 41767530.
Population: Patients diagnosed with post-COVID syndrome
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.
Other
Franzini M, Vaiano F, Tirelli U, et al.. International Immunopharmacology, 2025. PMID 39657536.
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.
Randomized controlled trial · n = 73
He Y, Liu X, Zha S, et al.. International Immunopharmacology, 2024. PMID 39018686.
Population: Patients with post-acute sequelae of COVID-19
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.
Systematic review / meta-analysis · n = 424
Migliorini F, Giorgino R, Mazzoleni MG, et al.. European Journal of Orthopaedic Surgery & Traumatology, 2024. PMID 39579218.
Population: Patients with knee osteoarthritis, pooled from randomized trials comparing ozone with hyaluronic acid
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.
Narrative review · n = 271
Serra MEG, Baeza-Noci J, Abdala CVM, et al.. Medical Gas Research, 2023. PMID 37077114.
Population: Patients across 13 pooled clinical studies of medical ozone therapy in COVID-19
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.
Case report · n = 1
Valdenassi L, Rossi E, Corsetti MT, et al.. European Review for Medical and Pharmacological Sciences, 2022. PMID 36066166.
Population: Older adult with Sjögren syndrome
Reported finding: A single older patient with Sjögren syndrome reported reduced pain and fatigue after a course of oxygen-ozone major autohemotherapy.
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.
Systematic review / meta-analysis
Wen Q, Liu D, Wang X, et al.. International Wound Journal, 2022. PMID 34612569.
Population: People with chronic wounds and ulcers, mainly diabetic foot ulcers, pooled from 12 randomized trials
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.
Cohort study · n = 100
Tirelli U, Franzini M, Valdenassi L, et al.. European Review for Medical and Pharmacological Sciences, 2021. PMID 34604980.
Population: Patients with post-COVID fatigue
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.
Narrative review
Rowen RJ. Medical Gas Research, 2019. PMID 31898609.
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.
Randomized controlled trial · n = 80
Niu T, Lv C, Yi G, et al.. Medical Science Monitor, 2018. PMID 29611536.
Population: Patients with trauma-induced lumbar disc herniation
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.
Systematic review / meta-analysis · n = 212
Liu J, Zhang P, Tian J, et al.. Cochrane Database of Systematic Reviews, 2015. PMID 26505864.
Population: People with diabetic foot ulcers, pooled from 3 randomized controlled trials
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.
Controlled trial (non-randomized) · n = 15
Paoli A, Bianco A, Battaglia G, et al.. Physical Therapy in Sport, 2013. PMID 23623301.
Population: Competitive amateur male cyclists
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.
Randomized controlled trial · n = 140
Borrelli E, Diadori A, Zalaffi A, et al.. International Journal of Ophthalmology, 2012. PMID 23275905.
Population: Patients with dry age-related macular degeneration
Reported finding: In a randomized controlled trial of 140 patients, 27 sessions of major ozonated autohemotherapy over 12 months preserved visual acuity relative to multivitamin therapy and increased plasma antioxidant potential, with no loss of visual acuity in treated eyes versus substantial losses in controls.
Limitations: PubMed does not tag this as a randomized controlled trial, so the design is inferred from the abstract's own description; a co-author is a leading proponent of ozone therapy, and masking of outcome assessors is not described.
Systematic review / meta-analysis
Magalhaes FN, Dotta L, Sasse A, et al.. Pain Physician, 2012. PMID 22430658.
Population: Patients with chronic low back pain secondary to herniated disc
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.
Narrative review
Elvis AM, Ekta JS. Journal of Natural Science, Biology, and Medicine, 2011. PMID 22470237.
Reported finding: A general clinical review describing ozone's history, proposed mechanisms (antimicrobial action, immune stimulation), application methods, and the range of conditions it has been marketed for.
Limitations: A broad narrative review without a systematic search or a stated evidence grade for the conditions it lists; does not address EBO2 specifically.