Medical ozone · graded by use, four uses
Ozone Therapy (Medical Ozone)
Graded on: condition-specific endpoints The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score.: knee and back pain scores, diabetic foot ulcer closure; no trial of general health, aging or longevity.
Grade C: human trials exist, but they are small, mixed or not yet repeated. This is not a finding that it does not work. How to read a grade →
At a glance
Ozone therapy uses a mix of oxygen and ozone gas. Clinics inject it into joints or beside the spine, apply it to wounds, or mix it with a person's own blood. Small trials found less knee pain and back pain after injections, but the trials were of low quality. In the one well-controlled trial for diabetic foot ulcers, ozone did not heal more ulcers. No trial has tested ozone for general health or aging. The FDA calls ozone a toxic gas with no known medical use, and case reports describe serious harms.
- What was measured
- Knee pain and function scores after a course of ozone injections into the knee.
- How big
- Pain on the visual analog scale fell 2.16 points more with ozone than with placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received. after 8 weeks.Read from the summary of PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 28738079.
- Who it applies to
- 98 adults with symptomatic knee osteoarthritis in one trial; trial quality across the knee studies was rated fair or poor. Other uses are graded separately on this page.
- Safety
- Case reports describe gas embolism, brain injury and infections after ozone treatments.
- Compared with
- Placebo injections.
- Certainty
- Grade C, resting on: Small randomized trials and pooled analyses for each use, mostly against other treatments; no trial for general health or aging.
- What would change this grade
- Could rise to B with: Multicenter double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends. randomized trial of ozone injections against saline injections. Who: Adults with knee osteoarthritis, at least 150 per arm. Measured: Pain and function on a validated scale, with a measured walking or strength test. Length: At least 6 months.
- Cost
- No price recorded yet.
- Sources
- 10 studies cited on this record, listed under Sources.
The C is shared by two of the four uses graded on this record, each on its own evidence. The other two carry their own letters.
As studied, and the trials
Lopes de Jesus et al. (PLoS One, 2017; PMID 28738079): double-blind, placebo-controlled, 98 patients, 8 weeks; pain, function and quality of life scores improved more with ozone. Nazarieh et al. (J Bodyw Mov Ther, 2024; PMID 38763606): double-blind, placebo-controlled, 33 patients and 42 knees, all doing home exercise; pain and function stayed better with ozone at 1 and 6 months. Sconza et al. (Arthroscopy, 2020; PMID 31679646): of 11 randomized trials with 858 patients, none reached good quality, 2 were fair and the rest poor. Migliorini et al. (Eur J Orthop Surg Traumatol, 2024; PMID 39579218): against hyaluronic acid, pain was no different at 4 to 6 months. Two small placebo-controlled trials on a self-reported endpoint, with trial quality rated fair or poor: C. A 2026 trial of ozone mixed with dextrose and magnesium is not counted here, because it did not test ozone alone.
As studied, and the trials
Sucuoglu and Soydas (J Back Musculoskelet Rehabil, 2021; PMID 33843663): double-blind, 38 patients, ozone beside the spine against a very low ozone dose as placebo, both on top of conservative care; pain and disability fell more with ozone, most at one month after treatment. Chang et al. (J Back Musculoskelet Rehabil, 2024; PMID 38905033): pooled trials of ozone injected into the disc; treatment success at 6 months was higher than with steroid injections and pain fell more than with medications, with results similar to microdiscectomy. Magalhaes et al. (Pain Physician, 2012; PMID 22430658): the trials pooled were mainly against active treatments and no placebo-controlled trial was found. One small placebo-controlled trial, not repeated, on a self-reported endpoint: C.
As studied, and the trials
Wainstein et al. (Diabetes Technol Ther, 2011; PMID 21751891): the one double-blind, sham-controlled trial; Full wound closure did not differ by assigned group (41 against 33 percent), and only the per-protocol subset favored ozone. Cacciatore et al. (Med Sci (Basel), 2026; PMID 42346828): umbrella review of meta-analyses A study that pools the numbers from several trials into one combined estimate. against inactive controls; ozone was not superior for ulcer healing (RR 1.69, 95% CI 0.90 to 3.17), low certainty. Filho et al. (J Wound Care, 2024; PMID 39630555): six trials pooled found more healed ulcers, with considerable risk of bias. The cleanest tests did not show a healing benefit: D on Route 2 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale..
Read the grade that matches your goal. How EBL grades by use →
A letter describes the human evidence, not the product, the manufacturer, or the intervention's worth.
See the full evidence record →Ozone Therapy (Medical Ozone), graded on condition-specific endpoints: knee and back pain scores, diabetic foot ulcer closure; no trial of general health, aging or longevity: what the randomized trials measured, in whom, and what they did not show.
Why this letter
Why this gradeGrade C, small or unreplicated trials. The reasoning, and what the grade does not cover.
Grade C at the headline, from its best-supported uses, knee and back pain from injections; each use carries its own letter below. Knee osteoarthritis pain: two small placebo-controlled trials favored ozone (PMIDs 28738079, 38763606), but independent review rated the trials fair or poor (PMID 31679646): C. Back pain from a herniated disc: one small placebo-controlled trial (PMID 33843663) and pooled trials against other treatments (PMID 38905033): C. Diabetic foot ulcers: the sham-controlled trial missed its main analysis (PMID 21751891) and pooled trials against inactive controls found no healing benefit (PMID 42346828): D, tested. General health, aging or longevity: no randomized trial: D, not tested.
WHY NOT Bno use has well-designed placebo-controlled trials supporting each other, and pain is a self-reported endpoint.
WHAT THIS GRADE DOES NOT COVERdental uses such as periodontitis and wisdom tooth surgery, which the 2026 umbrella review included and this record does not grade; ozonated oils on the skin; and ozone sauna cabinets.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
Evidence notes: randomized trial, meta-analysis, not independently replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away., mixed
Endpoint graded: Condition-specific endpoints: knee and back pain scores, diabetic foot ulcer closure; no trial of general health, aging or longevity (self_report)
Last reviewed: November 2026
The trial that would change this grade.
A positive trial of this shape, supported by further trials, would move this entry to B.
Why the current trials fall short
The placebo-controlled knee trials are small and rated fair or poor. A larger well-run trial against saline, repeated, would test whether the pain effect holds.
Why people believe itOne human source; no published case reports of benefit; nine reports of harm.
The case for ozone is that a small, controlled oxidant dose triggers the body's own antioxidant and anti-inflammatory responses.
What supporters point to, and what each source actually shows. None of it is enough to move this letter higher; the trial described above under Evidence wanted is what would.
- Human trial, a different useIn knee osteoarthritis, a placebo-controlled trial found less pain after ozone injections, which clinics extend to other conditions without trials of their own. PMID 28738079
A case report describes what happened to one or a few patients. It cannot show the treatment caused the change, and reports of success are published more often than reports of failure.
A PubMed search in November 2026 found no published case report of benefit for this use.
- A 64-year-old woman developed leg weakness and loss of vision after intravenous ozone, consistent with arterial gas embolism; she recovered fully with hyperbaric oxygen. PMID 42365944
- Three patients had brain symptoms, including loss of consciousness or vision, immediately after neck or back ozone injections; all recovered within 48 hours, and two had a patent foramen ovale. PMID 33657263
- A healthy 55-year-old man needed 48 hours on a ventilator for brain injury attributed to an ozone injection under the skin, then recovered completely. PMID 41492606
- A 54-year-old woman had air inside the skull after an epidural ozone injection during a disc procedure, and recovered within a day. PMID 39411376
- A patient had air inside the skull and meningitis after a lumbar ozone injection reached the fluid around the spinal cord. PMID 42516792
- A 65-year-old man developed a staphylococcal shoulder joint infection needing surgery after ozone therapy; the authors state the report does not establish cause. PMID 41728388
- A patient developed infection of the spine and pelvic joint with abscesses after four sessions of ozone therapy for low back pain. PMID 36814395
- A patient developed tuberculosis of the spine after ozone was injected into a disc. PMID 35437492
- A 57-year-old woman had free air in the abdomen after a session of ozone therapy for low back pain, managed without surgery. PMID 40233642
Searched PubMed, November 2026: 69 case report record(s) returned. Screened by title and abstract. The harm reports with an abstract are cited in the safety section; one stroke report has no abstract and is not cited. Most other records describe ozone used as a treatment in single patients, not harms.
ClinicalTrials.gov, the public registry run by the U.S. National Library of Medicine, lists studies that are recruiting volunteers. The link below searches it for Ozone therapy among studies recruiting now. EBL has no relationship with any listed study and receives no payment for this link.
Search recruiting studies of Ozone therapy on ClinicalTrials.gov
Dose, form and timing
Pain and function on a validated scale before and after a course, set with the treating clinician.
As studiedDose, form, population and duration for every use.
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
Safety
The FDA regulation on ozone states that it is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy (21 CFR 801.415). Case reports describe arterial gas embolism with temporary blindness after intravenous ozone (PMID 42365944), brain injury attributed to ozone after injections (PMIDs 33657263, 41492606), air inside the skull after spinal injections (PMIDs 39411376, 42516792), infections of the shoulder joint and spine after ozone treatments (PMIDs 41728388, 36814395, 35437492), and air in the abdomen after back injections (PMID 40233642). Use is a decision for a clinician, especially with a heart defect such as a patent foramen ovale, which two of the reported brain injury cases had.
Harms suspected from case reports, none documented in trials. Each caution on this record, sorted by what it rests on.
None recorded.
- 9 published case reports of harm, described in the record's reports of harm (PMID 42365944 PMID 33657263 PMID 41492606 PMID 39411376 PMID 42516792 PMID 41728388 PMID 36814395 PMID 35437492 PMID 40233642)
None recorded.
None recorded.
Does not apply: human harm data are listed above.
Grade history
How this letter has changedLatest: No. 422 · November 2026 · First graded.
Ozone therapy now has a record, graded by use. Two small placebo-controlled trials found less knee pain after injections (Lopes de Jesus et al., PLoS One, 2017; PMID 28738079), with trial quality rated fair or poor: C, and back pain from a herniated disc is also C. The one sham-controlled trial for diabetic foot ulcers missed its main analysis (Wainstein et al., Diabetes Technol Ther, 2011; PMID 21751891), and pooled trials against inactive controls found no healing benefit (Cacciatore et al., Med Sci (Basel), 2026; PMID 42346828): D, tested. No trial has tested ozone for general health or aging.PMID 28738079 PMID 21751891 PMID 42346828
Every change to a letter on this site is dated and published. The full evidence log →
Sources
- Citations
- Every paper cited on this page is matched to its PubMed record on every build.
- Retractions
- None of these papers is retracted or under a journal expression of concern. PubMed is checked again on every build.
- Read against the papers
- November 2026. By a language model (AI-assisted reading), not yet reviewed by a clinician.
- Outside review
- Not yet done. No reviewer outside EBL has checked this record.
What each of these checks can and cannot show: evidence integrity.
Primary evidenceTen papers, each linked to its PubMed record.
Lopes de Jesus et al. (PLoS One, 2017; PMID 28738079): double-blind placebo-controlled trial, 98 patients with knee osteoarthritis; pain, function and quality of life improved more with injected ozone over 8 weeks. Nazarieh et al. (J Bodyw Mov Ther, 2024; PMID 38763606): double-blind placebo-controlled trial, 33 patients with knee osteoarthritis on home exercise; benefit held at 1 and 6 months. Sconza et al. (Arthroscopy, 2020; PMID 31679646): systematic review A review that searches for every study on a question using a method set in advance, then assesses them together. of 11 knee trials, none of good quality. Migliorini et al. (Eur J Orthop Surg Traumatol, 2024; PMID 39579218): ozone and hyaluronic acid gave similar knee pain at 4 to 6 months. Sucuoglu and Soydas (J Back Musculoskelet Rehabil, 2021; PMID 33843663): double-blind trial, 38 patients with acute lumbar disc herniation; pain and disability fell more with ozone beside the spine. Chang et al. (J Back Musculoskelet Rehabil, 2024; PMID 38905033): pooled trials; ozone into the disc did better than steroid injections at 6 months. Magalhaes et al. (Pain Physician, 2012; PMID 22430658): pooled trials of ozone for disc-related back pain, mainly against active treatments, with no placebo-controlled trial. Wainstein et al. (Diabetes Technol Ther, 2011; PMID 21751891): double-blind sham-controlled trial, 61 patients with diabetic foot ulcers; full wound closure in 41 against 33 percent, not significant. Cacciatore et al. (Med Sci (Basel), 2026; PMID 42346828): umbrella review of seven meta-analyses against inactive controls in four conditions; certainty low or very low for every outcome, and no healing benefit for diabetic foot ulcers. Filho et al. (J Wound Care, 2024; PMID 39630555): six diabetic foot ulcer trials pooled, more ulcers healed, with considerable risk of bias.
Evidence Based Longevity, Inc. is owner-operated and edited by Arnold Sandlow, D.C., a California-licensed chiropractor. Evidence Based Longevity publishes in English only · Machine translations are not produced or reviewed by EBL for accuracy
How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
("ozone therapy"[tiab] OR ozonated[tiab] OR "oxygen-ozone"[tiab]) AND (randomized controlled trial[pt] OR meta-analysis[pt])PubMed watch: does a new study change the grade? (nothing new)
No new paper matching the search behind this grade has been added to PubMed since November 2026.
Last run November 2026. A letter on EBL moves only after a logged review. A new paper never moves a letter by arriving: it is read, the answer is written here, and any change to the letter is published in the evidence log.
For each trial behind a letter on this page, the funding its PubMed record lists. "No funder" means PubMed lists none, not that the trial had no funding.
- “Comparison between intra-articular ozone and placebo in the treatment of knee...” (PMID 28738079): PubMed lists no funder for this trial. The PubMed record carries a competing-interest statement.
- “The effect of intra-articular ozone injection combined with home-based exercise on...” (PMID 38763606): PubMed lists no funder for this trial. The PubMed record carries a competing-interest statement.
- “Does paravertebral ozone injection have efficacy as an additional treatment for acute...” (PMID 33843663): PubMed lists no funder for this trial.
- “Efficacy of ozone-oxygen therapy for the treatment of diabetic foot ulcers” (PMID 21751891): PubMed lists no funder for this trial.
Disclosure
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