OBJECTIVE: To conduct a systematic review and meta-analysis to assess the effectiveness of ozone therapy in oral ulcers healing when compared to placebo or active treatments.
METHODS: The search was carried out using PubMed, EMBASE, Scopus, and Lilacs databases. Clinical trials involving human participants were included. The Risk Ratio (RR) and the standardized mean difference (SMD) with 95%CI (confidence interval) were calculated. The ROBINS-I (risk of bias in non-randomized studies of interventions) and RoB2 (risk of bias tool for randomized trials) assessment tool was used to detect bias.
RESULTS: After the selection process, 12 studies were included. The meta-analysis showed that ozone therapy helps to reduce the size of the traumatic and autoimmune ulcers (RR=-0.44; 95% CI -0.71,-0.17; I2=0%) in comparison to placebo. Regarding pain reduction, ozone was superior to placebo (RR = 1.29, 95% CI -1.6 to -0.95); I2=0%), and equivalent to topical corticosteroid and laser photobiomodulation (RR = 0.26, 95% CI -0.27,0.78, p = 0.34).
CONCLUSIONS: Ozone therapy is an alternative for accelerating healing and reducing pain for both traumatic and autoimmune ulcers. However, the quality of evidence is limited.
CONCLUSIONS: Oral ulcerations are usually painful and impact quality of life requiring different approaches to boost wound healing and reduce symptoms. For this purpose, ozone therapy is a promising strategy.

OBJECTIVE: This study aimed to assess the effectiveness of ozone therapy in treating Diabetes-related Foot Ulcer (DFU) and its outcomes.
METHODS: A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and ProQuest databases for published studies evaluating the use of ozone as an adjunct treatment for DFU, from inception to December 21, 2022. The primary outcome measure was the change in wound size after the intervention compared to pretreatment. Secondary outcomes included time to complete ulcer healing, number of healed patients, adverse events, amputation rates, and hospital length of stay. Quantitative data synthesis for the meta-analysis was performed using a random-effects model and generic inverse variance method, while overall heterogeneity analysis was conducted using a fixed-effects model. Interstudy heterogeneity was assessed using the I2 index (<50%) and the Cochrane Q statistic test. Sensitivity analysis was performed using the leave-one-out method.
RESULTS: The meta-analysis included 11 studies comprising 960 patients with DFU. The results demonstrated a significant positive effect of ozone therapy on reducing foot ulcer size (Standardized Mean Difference (SMD): -25.84, 95% CI: -51.65 to -0.04, p = 0.05), shortening mean healing time (SMD: -38.59, 95% CI: -51.81 to -25.37, p < 0.001), decreasing hospital length of stay (SMD: -8.75, 95% CI: -14.81 to -2.69, p < 0.001), and reducing amputation rates (Relative Risk (RR): 0.46, 95% CI: 0.30-0.71, p < 0.001), compared to standard treatment.
CONCLUSIONS: This meta-analysis indicates that ozone therapy has additional benefits in expediting complete DFU healing, reducing the amputation rates, and decreasing hospital length of stay, though its effects do not differ from standard treatments for complete ulcer resolution. Further research is needed to address the heterogeneity among studies and to better understand the potential beneficial effects of ozone therapy.

Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.

The objective of this study is to evaluate the effectiveness and safety of ozone therapy (OT) in the treatment of knee osteoarthritis (KOA), which is the most common form of the disease. We analysed systematic reviews (SRs) of randomised controlled trials (RCTs) using the \"A MeaSurement Tool to Assess systematic Reviews\" (AMSTAR2) instrument to evaluate their quality. We developed a narrative synthesis report with eight SRs (15 RCTs/3,685 patients) to summarise the findings. The AMSTAR2 analysis indicated that all reviews had critically low confidence ratings. Statistically significant effects in pain reduction using OT compared to placebo groups were reported in three SRs. OT was shown to be comparable to other therapies in one SR and not superior in the other five. Six SRs highlighted the need for additional RCTs with improved methodological quality to confirm the efficacy of OT for KOA. SRs found fewer consistent effects for improving joint function. Regarding safety, seven SRs reported a low prevalence of minor adverse events linked with OT. Finally, this umbrella review highlights the beneficial effects and safety of OT in the treatment of KOA, particularly in pain control. The low methodological quality of RCTs and SRs limits the possibility of drawing conclusions on the effectiveness of the procedure in comparison to other therapies. Ensure adequate compliance with guidelines such as Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR2 has the ability to improve the quality of SRs in this area.

Breast cancer is the most prevalent form of cancer in women. Despite significant advances in conventional treatment, additional safer complementary treatment options are needed. Recently, ozone therapy has been considered as a type of medical adjunctive treatment that could inhibit cancer cell survival and reduce chemoresistance. However, only a few studies have been conducted on its use in breast cancer, and the optimal dosage and time of administration are unknown. Currently, preclinical studies suggest that ozone alone or in combination with chemotherapy is an effective method for inhibiting breast cancer cell growth. However, rather than investigating the effects of ozone as an antitumor therapy, current clinical trials have generally assessed its effect as an adjunctive therapy for reducing chemotherapy-induced side effects, increasing oxygen tension, normalizing blood flow, restoring blood lymphocytes more rapidly, and reducing fatigue symptoms. In this article, the use of ozone as a medical adjunctive treatment for breast cancer and its role in integrative therapy are summarized and discussed.

UNASSIGNED: Complex regional pain syndrome (CRPS) is characterized by extreme pain in a limb disproportional to the clinical history or physical findings accompanied by the signs of autonomic dysfunction. The pathophysiology of CRPS is obscure, making it challenging to treat. Treatment options include medications, physical therapy, and psychological support. In some cases, surgery or other minimally-invasive procedures such as nerve blocks may be recommended, while several novel treatments, such as ozone therapy, lack sufficient clinical evidence.
UNASSIGNED: A 40-year-old man with CRPS was referred to our clinic with pain in his right arm and left lower leg. The patient had a history of trauma to the ulnar nerve and had undergone a sural to ulnar nerve autograft surgery. After the surgery, the patient\'s symptoms began, primarily in the right arm. Despite receiving conventional drugs, multiple nerve blocks, and lidocaine patches, the patient\'s symptoms persisted. In addition, we tried medical ozone for 14 sessions along with ketamine infusion, but these treatments were also ineffective.
UNASSIGNED: We emphasize the importance of studying and developing more effective treatments for CRPS and suggest that further randomized clinical trials are needed to determine whether ozone therapy is effective for patients with severe, intractable CRPS symptoms.

Low back pain (LBP) is a common pathology, and its high prevalence has led to the emergence of alternative options that have gained popularity without objective epidemiological evaluations. This work seeks to clarify the utility of ozone in the treatment of LBP.
A systematic literature search was conducted following the principles by PRISMA. The search included articles published up to June 2023. Each of the authors reviewed the abstract of the articles and applied the inclusion and exclusion criteria.
A total of 28 articles were selected: 18 prospective randomized clinical studies, 3 systematic reviews plus meta-analysis, and 6 retrospective case series studies.
The treatment of LBP is complex. Advancements have been made in recent years from biomechanical and pathophysiological perspectives, but ozone therapy is not considered a treatment option. Techniques that involve the use of ozone fall into the category of empirical options. International guidelines for LBP exclude ozone therapy. It is advisable to conduct further studies under strict parameters to better evaluate its outcomes.

BACKGROUND: Ozone is a naturally occurring unstable compound with three oxygen atoms that generally transforms into an oxygen molecule, releasing one oxygen atom. This feature has been exploited in dentistry for numerous applications, including for periodontal diseases and peri-implantitis.
METHODS: This review was performed in relation to the PRISMA flow chart and was annotated in the PROSPERO register. PICO questions were used as research questions. The risk of bias in the non-randomized clinical trials was appraised using the ROBINS-I tool.
RESULTS: An electronic search found a total of 1073 records, in particular, 842 from MEDLINE/PubMed, 13 from Bio Med Central, 160 from Scopus, 1 from the Cochrane library databases, and 57 from the PROSPERO register. A total of 17 studies were included in the present systematic review. Information regarding the characteristics of the periodontal clinical and radiographic parameters for gaseous ozone, ozonate water, ozonate oil, and ozone gel, including clinical attachment loss (CAL) probing depth (PPD), bleeding on probing (BoP), plaque index (PI), gingival index (GI), and marginal bone levels (MBL), were obtained.
CONCLUSIONS: The studies included in this systematic review show different results regarding the ozone in periodontal treatment in association with or without SRP.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has rapidly swept across the world. As new knowledge regarding treatment options for COVID-19 has emerged, the use of ozone therapy in the context of SARS-CoV-2 infection as an integrative therapeutic option supplementary to standard treatment regimen has been assessed in the present literature. We reviewed, critically analyzed, and summarized all present published literature on ozone therapy in association with COVID-19 via the PubMed database. Various reports and studies on the use of ozone (major autohemotherapy, rectal ozone insufflation, ozone inhalation) in patients affected by COVID-19 indicate that ozone therapy may reduce morbidity and accelerate recovery, while exhibiting a high safety profile with no relevant adverse effects. Current literature suggests that integrating ozone therapy into the existing standard of care and best available therapy for the treatment of COVID-19 patients offers major advantages in terms of superior clinical outcome parameters and amelioration of laboratory results. Further prospective studies are warranted to guide the next steps in the clinical application of ozone therapy and examine its impact on the course of COVID-19.

Ozone (O3) is a reactive oxygen species (ROS) that can interact with cellular components and cause oxidative stress. Following said logic, if O3 induces such a stressful milieu, how does it exert antioxidant functions? This is mediated by controlled toxicity produced by low concentrations of O3, which enhance the cell\'s suppliance of antioxidant properties without causing any further damage. Therapeutic concentrations vary extensively, although 50 µg/mL is commonly used in experimental and clinical procedures, given that augmented concentrations might work as germicides or cause endogenous damage. O3 therapy has been shown to be effective when applied before or after traumatic renal procedures, whether caused by ischemia, xenobiotics, chronic damage, or other models. In this review, we focus on discussing the role of O3 therapy in different models of kidney damage associated with fibrosis, apoptosis, oxidative stress, and inflammation. We integrate and report knowledge about O3 in renal therapy, debunking skepticism towards unconventional medicine, explaining its proven therapeutic properties, and thus providing background for its use in further research as well as in clinical settings.