Non-Cochrane · umbrella · PM42346828

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

Cacciatore Stefano, Abbatecola Gabriele, Calvani Riccardo, et al. · Medical sciences (Basel, Switzerland) · 2026 · PubMed · doi:10.3390/medsci14020289

Findings

21 findings

Population
Patients with chronic periodontitis undergoing scaling and root planingOzone therapy as adjunct to scaling and root planingScaling and root planing without ozone (control)Clinical attachment levelMD -0.27 [-0.56, 0.01]
Very low
Downgraded: risk of bias, imprecision, inconsistency
9 studies · 439 participants
Patients with chronic periodontitis undergoing scaling and root planingOzone therapy as adjunct to scaling and root planingScaling and root planing without ozone (control)Plaque indexMD -0.05 [-0.15, 0.04]
Low
Downgraded: risk of bias, imprecision
7 studies · 254 participants
Patients with chronic periodontitis undergoing scaling and root planingOzone therapy as adjunct to scaling and root planingScaling and root planing without ozone (control)Probing pocket depthMD -0.26 [-0.48, -0.05]
Very low
Downgraded: risk of bias, imprecision, inconsistency
12 studies · 595 participants
Patients with chronic periodontitis undergoing scaling and root planingOzone therapy as adjunct to scaling and root planingScaling and root planing without ozone (control)Bleeding on probingMD -3.29 [-8.65, 2.06]
Low
Downgraded: risk of bias, imprecision
6 studies · 316 participants
Patients with chronic periodontitis undergoing scaling and root planingOzone therapy as adjunct to scaling and root planingScaling and root planing without ozone (control)Gingival indexMD -0.15 [-0.24, -0.07]
Low
Downgraded: risk of bias, imprecision
7 studies · 294 participants
Patients hospitalized for COVID-19Ozone therapyControl treatment (non-active)Intensive care unit admissionRR 0.44 [0.15, 1.33]
-64 [-97, 38] per 1000
Low
Downgraded: imprecision
3 studies · 180 participants
Patients hospitalized for COVID-19Ozone therapyControl treatment (non-active)Length of hospital stayMD -0.7 [-4.1, 2.7]
Very low
Downgraded: imprecision, inconsistency
2 studies · 122 participants
Patients hospitalized for COVID-19Ozone therapyControl treatment (non-active)PCR positivity
at follow-up
RR 0.07 [0.01, 0.34]
-434 [-462, -308] per 1000
Low
Downgraded: imprecision
2 studies · 90 participants
Patients hospitalized for COVID-19Ozone therapyControl treatment (non-active)MortalityOR 0.73 [0.32, 1.68]
-15 [-38, 35] per 1000
Low
Downgraded: imprecision
3 studies · 180 participants
Patients with diabetic foot ulcersOzone therapyControl treatment (non-active)Adverse eventsRR 2.27 [0.48, 10.79]
GRADE not reported
Studies not reported
Patients with diabetic foot ulcersOzone therapyControl treatment (non-active)Reduction in ulcer areaMD -2.11 [-5.29, 1.07]
Very low
Downgraded: risk of bias, imprecision, inconsistency
2 studies · 111 participants
Patients with diabetic foot ulcersOzone therapyControl treatment (non-active)Ulcers healedRR 1.69 [0.9, 3.17]
138 [-20, 434] per 1000
Low
Downgraded: risk of bias, imprecision
2 studies · 111 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Quality of life
at 24 h
MD -11.24 [-12.73, -9.75]
Very low
Downgraded: risk of bias, imprecision
2 studies · 160 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Quality of life
at 7 days
MD -6.85 [-7.68, -6.02]
Very low
Downgraded: risk of bias, imprecision
2 studies · 160 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Mouth opening
at 72 h
MD 2.77 [-0.63, 6.17]
Very low
Downgraded: risk of bias, imprecision, inconsistency
4 studies · 266 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Swelling
at 7 days
SMD -0.87 [-2.31, 0.56]
Very low
Downgraded: risk of bias, imprecision, inconsistency
4 studies · 266 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Mouth opening
at 24 h
MD 2.74 [-1.93, 7.41]
Very low
Downgraded: risk of bias, imprecision, inconsistency
4 studies · 266 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Number of analgesics usedMD -3.8 [-4.38, -3.22]
Very low
Downgraded: risk of bias, imprecision
3 studies · 226 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Mouth opening
at 7 days
MD 1.42 [-1.34, 4.18]
Very low
Downgraded: risk of bias, imprecision, inconsistency
4 studies · 266 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Quality of life
at 72 h
MD -11.08 [-12.08, -10.08]
Very low
Downgraded: risk of bias, imprecision
2 studies · 160 participants
Patients undergoing surgery for impacted mandibular third molarOzone therapyControl treatment (non-active)Swelling
at 72 h
SMD 0.63 [-1.42, 2.69]
Very low
Downgraded: risk of bias, imprecision, inconsistency
4 studies · 266 participants

Included primary studies 7

Open in Studies
StudyYearAlso included byOutcomes it informs hereTrial data
Chaudhry 2021
Efficacy of adjuvant ozone therapy in reducing postsurgical complications following impacted mandibular third-molar surgery: A systematic…
PMID:34579810
2021this review onlynot statednot extracted yet
Filho 2024
Ozone therapy as a treatment for diabetic foot ulcers: a systematic review and meta-analysis.
PMID:39630555
2024this review onlynot statednot extracted yet
Jafari-Oori 2022
Efficacy of ozone adjuvant therapy in COVID-19 patients: A meta-analysis study.
PMID:36438064
2022this review onlynot statednot extracted yet
Liu 2015
Ozone therapy for treating foot ulcers in people with diabetes.
PMID:26505864
2015this review onlynot statednot extracted yet
Liu 2025
Effects of ozone therapy as an adjuvant in the treatment of periodontitis: a systematic review and meta-analysis.
PMID:40038617
2025this review onlynot statednot extracted yet
Moraschini 2020
Ineffectiveness of ozone therapy in nonsurgical periodontal treatment: a systematic review and metaanalysis of randomized clinical trials.
PMID:32399735
2020this review onlynot statednot extracted yet
Shang 2023
Benefits of ozone on mortality in patients with COVID-19: A systematic review and meta-analysis.
PMID:36513208
2023this review onlynot statednot extracted yet

Review question

ElementPlanned (methods)Found (results)
PopulationHuman participants with any medical conditionFour populations across 7 meta-analyses: chronic periodontitis (n=2 meta-analyses), hospitalized COVID-19 (n=2), diabetic foot ulcers (n=2), impacted mandibular third-molar surgery (n=1)
InterventionOzone therapy: medical ozone in any form (systemic administration, intra-articular injection, rectal insufflation, topical application) with therapeutic intentOzone therapy by local, systemic or combined routes (ozonated water or gas, autohemotherapy, rectal insufflation, nebulization, topical gel); dose not standardized
ComparisonNon-active controls: placebo, saline, sham treatment or standard careControl treatment, placebo or standard care
OutcomesClinical efficacy endpoints relevant to the treated condition; safety endpoints (incidence and severity of adverse events)Periodontal outcomes (probing pocket depth, gingival index, bleeding on probing, plaque index, clinical attachment level); COVID-19 outcomes (PCR positivity, length of hospital stay, ICU admission, mortality); diabetic foot ulcer healing, ulcer area, adverse events; third-molar outcomes (swelling, mouth opening, quality of life, analgesic use)
Study designsSystematic reviews with meta-analyses of randomized clinical trialsMeta-analyses of RCTs (n=7); outcome-level GRADE synthesis from one retained meta-analysis per indication
TimingNot specifiedNot specified