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Research · Therapies

Ozone therapy

Small sham-controlled trials found ozone injections eased back and knee osteoarthritis pain, but reviews rate nearly all ozone trials low or critically low in quality. Gains over usual care for back pain were small. COVID-19 deaths and foot ulcer healing did not differ. FDA calls ozone a toxic gas. Gas embolism, stroke and spinal infection appear in case reports.

Checked 2026-11-13
Status
The FDA's device rule describes ozone as a toxic gas with no known useful medical application in specific, adjunctive or preventive therapy, and treats a device used for a medical condition without proof of safety and effectiveness as adulterated or misbranded [1]. Medical ozone is given as a mix of oxygen and ozone, injected in the trials beside the spine, into the knee or into spinal discs [3][5][6]. The sources located name no separate US license for ozone therapy.
Also called
ozone therapy, medical ozone, oxygen-ozone therapy, O2-O3 therapy, ozonotherapy, ozone injection, prolozone, intradiscal ozone, paravertebral ozone, ozone autohemotherapy, major autohemotherapy, MAH, ozonated blood, ozone sauna, rectal ozone insufflation, ozonated oil
Used for
back pain, sciatica, herniated disc, knee osteoarthritis, joint pain, shoulder pain, wound healing, diabetic foot ulcers, infections, COVID-19, Lyme disease, immunity, inflammation, cancer, anti-aging, detox, circulation

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help3

Reported risks4

What it is used for, and what was found

Shown to help3

Limited

Low back pain and herniated disc, compared with sham injections

Two small double-blind trials found ozone injections beside the spine eased back pain and disability more than injections of oxygen or very dilute ozone.

Compared with paraspinal injections of pure oxygen [2]; paravertebral injections of very dilute ozone, 0.1 µg/mL [3]

The numbers and sources
Effect
In chronic discogenic low back pain, pain on the visual analog scale fell 5.6 points with ozone and 2.4 with pure oxygen, and the Oswestry disability score fell 19.07 and 7.8 points (P < 0.001), with exercise in both groups [2]. In acute lumbar disc herniation, pain and disability scores were lower with ozone than with placebo at 15 and 30 days and one month after treatment ended (P < 0.05), added to conservative treatment [3].
Population
30 adults with MRI-confirmed chronic discogenic low back pain [2]. 38 adults with acute lumbar disc herniation [3].
Sources
[2], [3]
Caveats
Two small single-center trials with follow-up of 3 months or less. Pure oxygen and dilute ozone are injected gases themselves, so neither control is inert.
Moderate

Herniated lumbar disc, injection into the disc

Shown in pooled trials to give higher treatment success than steroid injections and more pain relief than medications at 6 months or more, with results similar to microdiscectomy.

Compared with steroid injections [5]; conventional medications [5]; microdiscectomy [5]

The numbers and sources
Effect
At 6 months, treatment success was higher than with steroid injections (OR 3.95, 95% CI 2.44 to 6.39). Pain fell more than with conventional medications at 6 months (SMD 1.65, 95% CI 1.08 to 2.22) and 12 months (SMD 1.52). At 18 months, pain did not differ from microdiscectomy (SMD -0.05, 95% CI -0.67 to 0.57) [5].
Population
People with herniated lumbar discs in trials searched to January 2024 [5].
Sources
[5]
Caveats
None of these comparisons was against a sham injection, so participants knew which treatment they had. A separate 2025 meta-analysis on disc injections of ozone has been retracted and is not used here.
Limited

Knee osteoarthritis, compared with placebo

Limited evidence: one double-blind trial and three reviews found less knee osteoarthritis pain than placebo, and an umbrella review rated every review critically low in confidence.

Compared with placebo injections [6][7]

The numbers and sources
Effect
After 8 weeks of injections, pain was 2.16 points lower than placebo on the visual analog scale (95% CI 0.42 to 3.89), and the Lequesne index, WOMAC scores and several quality of life scores improved more. The Timed Up and Go test did not differ [6]. An umbrella review of 8 reviews covering 15 trials found 3 reporting significant pain reduction against placebo, while 5 found ozone no better than other therapies, with less consistent effects on joint function [7].
Population
98 adults with symptomatic knee osteoarthritis in Brazil [6]. 8 systematic reviews of 15 trials with 3,685 patients [7].
Sources
[6], [7]
Caveats
All 8 reviews had critically low confidence ratings on AMSTAR 2 [7]. The placebo trial lasted 8 weeks [6].

Mixed results3

Moderate

Low back pain, compared with usual care and other treatments

Mixed results: pooled trials found a small function gain at one month against usual care, no lasting pain difference, and no difference in excellent or poor outcomes.

Compared with usual care and other treatments the review abstract does not list [4]

The numbers and sources
Effect
Across 9 studies, disability on the Oswestry index favored ozone overall (SMD -0.28, 95% CI -0.51 to -0.06), at one month only, with no difference at 2 weeks or 6 months. Pain favored ozone overall by a small amount (SMD -0.12, 95% CI -0.24 to -0.01), and subgroup and sensitivity analyses found no difference. Excellent outcomes (OR 0.95, 95% CI 0.54 to 1.67) and poor outcomes (OR 1.25, 95% CI 0.66 to 2.37) did not differ [4].
Population
1,711 participants with low back pain in 9 studies [4].
Sources
[4]
Caveats
The reviewers describe the benefit over usual care as limited and the results as inconsistent [4].
Moderate

Joint and muscle pain, compared with corticosteroid injections

Mixed results: across musculoskeletal conditions, steroid injections eased pain more in the short term, while in knee osteoarthritis alone ozone eased pain more.

Compared with corticosteroid injections [8][9]

The numbers and sources
Effect
Across 11 studies of musculoskeletal pain of several kinds, short-term pain fell more with corticosteroid injections (d 0.31, 95% CI 0.01 to 0.60), and medium-term pain did not differ (d -0.17, 95% CI -0.42 to 0.07) [8]. In 7 knee osteoarthritis trials, ozone injections reduced pain more than corticosteroid injections in the short and medium term and improved function in the medium term [9].
Population
534 people with musculoskeletal pain in 11 studies [8]. 409 people with knee osteoarthritis in 7 trials [9].
Sources
[8], [9]
Caveats
Both reviews describe the included trials as limited in quality [8][9]. The knee review abstract gives no effect sizes [9].
Moderate

Diabetic foot ulcers

Mixed results: a Cochrane review found no difference in ulcer healing against usual care, while a later review reported more healed ulcers in trials at considerable risk of bias.

Compared with usual care [10]; antibiotics [10]; control treatments the review abstract does not describe [11]

The numbers and sources
Effect
Added to usual care, ozone did not change the number of ulcers healed (RR 1.69, 95% CI 0.90 to 3.17), ulcer area (MD -2.11 cm²) or amputations, in 2 trials. Against antibiotics, ulcer area shrank more and hospital stay was 8 days shorter, and healed ulcers did not differ over 20 days (RR 1.10, 95% CI 0.87 to 1.40) [10]. A later review of 6 trials reported higher healing rates and shorter hospital stays with ozone [11].
Population
212 people with diabetes in 3 trials [10]. 6 trials [11].
Sources
[10], [11]
Caveats
The Cochrane reviewers found three small trials with unclear methods and drew no firm conclusion [10]. The later review found considerable risk of bias [11].

Not shown to help1

Limited

COVID-19

Limited evidence: pooled trials found ozone did not shorten hospital stays or reduce intensive care admissions or deaths from COVID-19, though fewer PCR tests stayed positive.

Compared with placebo, sham, saline or standard care [12]

The numbers and sources
Effect
In meta-analyses of randomized trials, ozone therapy lowered PCR positivity at follow-up (RR 0.07, 95% CI 0.01 to 0.34), which the reviewers judged a clinically unimportant surrogate. Hospital stay, intensive care admission and mortality did not differ [12].
Population
Meta-analyses of trials in patients with COVID-19, within an umbrella review of 7 meta-analyses [12].
Sources
[12]
Caveats
Certainty was low or very low for every outcome in the umbrella review, and safety outcomes were reported inconsistently [12].

Claimed, not studied in people1

Untested

Cancer, anti-aging, detox and chronic infections

Not studied in people for these claims in controlled trials located. They rest on proposed hormetic, antioxidant and immune effects of ozone.

No study in people. This rests on how it acts in the body.

The numbers and sources
Effect
An umbrella review notes that ozone therapy has been proposed across many conditions on the basis of hormetic, antioxidant and immune-modulating effects. The meta-analyses of randomized trials it located covered only periodontitis, COVID-19, diabetic foot ulcers and wisdom tooth surgery [12]. The FDA's device rule states ozone has no known useful medical application in preventive or adjunctive therapy [1].
Population
No study population for these claims. An umbrella review of meta-analyses of randomized trials [12].
Sources
[12], [1]
Caveats
A proposed mechanism is not a measured effect in people. No trial located measured toxins removed, aging or cancer outcomes.

Protocols studied

The knee placebo trial injected 20 µg/mL of ozone into the joint over 8 weeks [6]. The back trials gave 8 paravertebral injections of 30 mL at 20 to 25 µg/mL, twice a week [3], or 3 weekly ultrasound-guided paraspinal injections at 20 µg/mL alongside exercise [2]. Disc trials injected ozone into the herniated disc [5].

Risks

Reported risks4

ModerateHow often is not known

Breathing ozone, the FDA position

FDA states ozone is a toxic gas with no known useful medical application, and that breathing it irritates the airways and can cause delayed fluid in the lungs.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The FDA's device rule states ozone's main effect is irritation of the mucous membranes, that lung irritation can cause pulmonary edema delayed by hours, and that smell is an unreliable warning because the nose quickly stops detecting it. It caps ozone from devices at 0.05 parts per million in occupied spaces [1].
Population
A federal regulation [1].
Sources
[1]
Caveats
The rule addresses ozone in air and ozone devices. It does not report rates of harm from ozone injected in medical procedures.
ModerateHow often is not known

Minor effects in trials

Reviews of knee osteoarthritis trials reported a low prevalence of minor adverse events, and one placebo trial recorded only puncture accidents.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Seven of 8 systematic reviews of ozone for knee osteoarthritis reported a low prevalence of minor adverse events [7]. In a 98-person placebo-controlled trial, adverse events occurred in 3 people, 1 given ozone and 2 given placebo, and all were puncture accidents [6]. An umbrella review found safety outcomes reported too inconsistently across conditions to draw firm conclusions [12].
Population
8 reviews of knee osteoarthritis trials [7]. 98 adults [6]. 7 meta-analyses [12].
Sources
[7], [6], [12]
Caveats
Rates were not given in the review abstracts.
LimitedHow often is not known

Gas embolism and stroke

Case reports: gas bubbles reached the brain during oxygen-ozone injection into a lumbar disc, causing multiple strokes.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
A 58-year-old woman developed limb weakness and speech disturbance during an intradiscal oxygen-ozone injection for disc herniation. Brain scans showed multiple gas emboli and strokes in both hemispheres, and echocardiography found a patent foramen ovale. She had improved significantly a year later. The authors note that oxygen-ozone therapy has been linked to gas embolism [13].
Population
One woman [13].
Sources
[13]
Caveats
Case reports give no rate.
LimitedHow often is not known

Spinal infection after disc injection

Case reports: eight cases of infection of the disc and spine after oxygen-ozone therapy, one of them fatal.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
A 55-year-old woman developed L4-L5 spondylodiscitis three months after intradiscal oxygen-ozone therapy and needed surgery and IV antibiotics. A literature review identified 8 cases in all, caused by Staphylococcus aureus, streptococci, E. coli, mycobacteria and other organisms. Outcomes were favorable in all but one, who died [14].
Population
8 published cases [14].
Sources
[14]
Caveats
Case reports give no rate.

Claims tested and not found

  1. That ozone helps diabetic foot ulcers heal. Added to usual care, healed ulcers did not differ (RR 1.69, 95% CI 0.90 to 3.17) [10].
  2. That ozone reduces deaths from COVID-19. Hospital stay, intensive care admission and mortality did not differ in meta-analyses of randomized trials [12].

Sources

  1. U.S. Food and Drug Administration. 21 CFR 801.415, Maximum acceptable level of ozone. Code of Federal Regulations. 2024. https://www.govinfo.gov/content/pkg/CFR-2024-title21-vol8/xml/CFR-2024-title21-vol8-sec801-415.xml
  2. Forogh B, Kazemi K. Ultrasound guided paravertebral ozone-oxygen injection versus pure oxygen for chronic discogenic low back pain: A double-blind randomized controlled trial. Journal of Back and Musculoskeletal Rehabilitation. 2026. https://doi.org/10.1177/10538127251379512
  3. Sucuoğlu H, Soydaş N. Does paravertebral ozone injection have efficacy as an additional treatment for acute lumbar disc herniation? A randomized, double-blind, placebo-controlled study. Journal of Back and Musculoskeletal Rehabilitation. 2021. https://doi.org/10.3233/bmr-200194
  4. Llombart-Blanco R, Mariscal G, Cordón V, et al. The Effectiveness of Ozone Infiltration on Patient-Reported Outcomes in Low Back Pain: A Systematic Review and Meta-Analysis. Life. 2024. https://doi.org/10.3390/life14111406
  5. Chang MC, Choo YJ, Denis I, et al. Effectiveness of intradiscal ozone injections for treating pain following herniated lumbar disc: A systematic review and meta-analysis. Journal of Back and Musculoskeletal Rehabilitation. 2024. https://doi.org/10.3233/bmr-240024
  6. Lopes de Jesus CC, dos Santos FC, de Jesus LMOB, et al. Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, double-blinded, placebo-controlled study. PLOS ONE. 2017. https://doi.org/10.1371/journal.pone.0179185
  7. Lino VTS, Marinho DS, Rodrigues NCP, Andrade CAF. Efficacy and safety of ozone therapy for knee osteoarthritis: an umbrella review of systematic reviews. Frontiers in Physiology. 2024. https://doi.org/10.3389/fphys.2024.1348028
  8. Arias-Vázquez PI, Guzzardo MN, Guzzardo DR, et al. Efficacy of ozone injections for reducing musculoskeletal pain in comparison with corticosteroid injections: A systematic review and meta-analysis. Journal of Back and Musculoskeletal Rehabilitation. 2024. https://doi.org/10.3233/bmr-230173
  9. Arias-Vázquez PI, Castillo-Avila RG, Hernández-Gil K, et al. Ozone injections reduce pain in knee osteoarthritis: a systematic review and meta-analysis. Medical Gas Research. 2026. https://doi.org/10.4103/mgr.medgasres-d-25-00088
  10. Liu J, Zhang P, Tian J, et al. Ozone therapy for treating foot ulcers in people with diabetes. Cochrane Database of Systematic Reviews. 2015. https://doi.org/10.1002/14651858.cd008474.pub2
  11. Filho MLES, Paggiaro AO, Fernandes de Carvalho V, Gemperli R. Ozone therapy as a treatment for diabetic foot ulcers: a systematic review and meta-analysis. Journal of Wound Care. 2024. https://doi.org/10.12968/jowc.2022.0189
  12. Cacciatore S, Abbatecola G, Calvani R, Veronese N. Effectiveness and Safety of Ozone Therapy in Humans: An Umbrella Review of Systematic Reviews with Meta-Analyses of Randomized Clinical Trials. Medical Sciences. 2026. https://doi.org/10.3390/medsci14020289
  13. Khosravi S, Mirzaasgari Z. Cerebral gas embolism and multifocal ischemic stroke during oxygen-ozone therapy: a case report. BMJ Neurology Open. 2024. https://doi.org/10.1136/bmjno-2024-000885
  14. Velluto C, Mazzella GG, Inverso M, et al. Spondylodiscitis Following Oxygen-Ozone Therapy: A Case Report of Lactobacillus iners Infection and a Systematic Literature Review. Diseases. 2026. https://doi.org/10.3390/diseases14030115

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