Napiórkowska, K., et al. (2025), Ozone as an Immunomodulator—New Therapeutic Possibilities in the Treatment of Immunodeficiencies—A Narrative Review, Current Issues in Molecular Biology, no. 47

Research Subject: Primary and secondary immunodeficiencies represent a growing clinical and public health challenge due to increased susceptibility to infections, impaired immune regulation, chronic inflammation, and disturbances in redox homeostasis. The pathophysiology of these disorders involves dysfunction of innate and adaptive immunity, altered cytokine production, oxidative stress, and reduced activity of antioxidant defense mechanisms. In recent years, attention has increasingly focused on the role of oxidative imbalance and chronic inflammation in weakening immune function. Ozone therapy, when used at controlled low doses, induces a hormetic response that triggers adaptive antioxidant pathways, modulates cytokine profiles, and enhances the activity of immune cells. Due to these properties, ozone has emerged as a potential adjunctive therapy aimed at restoring immune homeostasis and improving clinical outcomes in patients with immune disorders. Aim of Study: The aim of this review is to discuss the role of oxidative stress and immune dysregulation in the pathogenesis of immunodeficiencies and to provide an updated overview of current evidence regarding the therapeutic potential of ozone therapy. This article summarizes molecular mechanisms, biochemical effects, and clinical findings related to ozone-based interventions, with particular emphasis on cytokine modulation, redox balance, macrophage function, regulatory T cells (Treg), and NK cell activity. Materials and Methods: This review is based on scientific data retrieved from PubMed, Scopus, and Google Scholar. Included sources comprise randomized clinical trials, observational studies, meta-analyses, mechanistic studies, and review articles published between 1996 and 2025. Keywords used during the literature search included: “ozone therapy”, “immunomodulation”, “oxidative stress”, “inborn errors of immunity”, “secondary immunodeficiency”, “Treg cells”, “redox homeostasis”. Results: Analysis of current studies shows that controlled low-dose ozone (typically 10–40 μg/mL) activates the Nrf2/ARE antioxidant pathway, increases enzymatic defense (SOD, catalase, GPx), and reduces levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. Clinical trials report improved lymphocyte profiles, enhanced macrophage phagocytic function, increased Treg activity, and reinforced NK cell responses. Patients receiving ozone therapy demonstrate reductions in inflammatory markers (CRP, IL-6, D-dimer), improved redox balance, decreased infection frequency, and better overall immune performance. The therapynis generally well tolerated when administered within established safety guidelines. Conclusions: Available evidence indicates that ozone therapy may serve as a valuable adjunct in the management of immunodeficiencies by modulating immune responses, reducing oxidative stress, and restoring homeostatic balance. Although current clinical outcomes are promising, further multicenter randomized trials are needed to standardize dosing protocols, assess long-term effectiveness, and confirm safety.

Díaz, J., y cols. (2013), Efecto modulador de la ozonoterapia sobre la actividad del sistema inmune, Revista Cubana de Hematología, Inmunología y Hemoterapia, vol. 29, no. 2, pp. 143-153

Se ha probado la efectividad de la OT para modular el sistema inmune al inducir la producción de citocinas a partir de las células mononucleares de la sangre y regular el estrés oxidativo por estimulación de los sistemas antioxidantes celulares.

Diabetes

Menéndez, S., et al. (2016), Ozone Therapy in diabetes and its complications, Proceedings of the 5th. WFOT meeting, Mumbai, India, Journal of Ozone Therapy, vol. 2, no. 2, 3 p., doi: 10.7203/jo3t.2.2.2018.11127

In Diabetes mellitus, long-term complications, that cause morbidity and premature mortality, are characterized by microvascular and macrovascular diseases…

Ozone has been used as a therapeutical agent and beneficial effects have been observed…

Randomized controlled clinical trial where all patients provided a signed informed consent before being enrolled was performed. Adult hospitalized patients of both sex of any ethnic, with diagnosis of neuroinfectious diabetes foot suffering of ulcers of the feet and lower extremities were eligible to participate in the study. These patients must not meet any of the following criteria: severe septic conditions, hypersensibility to the medication that will be used, hepatic dysfunction, renal failure (serum creatinine level > 1.32 mol/L), pregnancy, cancer, current therapy with any immunosuppresive agent or anticonvulsant. Patients were randomized to two different groups of treatment: 1- control, 50 patients treated with antibiotic therapy, systemic and topically in the lesion (during 20 days), and 2- ozone, 52 patients treated daily with ozone, 20 sessions, by rectal insufflation (with an ozone dose of 10 mg, ozone concentration: 40 mg/L) and locally. The same biochemical parameters that were taking into account in the preclinical study were measured in plasma, at the beginning and at the end of the treatments, as well as the clinical evaluation of the lesions and length of hospitalization.

…ozone treatment improved glycemic control, and prevented oxidative stress, the increase of fructolysine content and advanced oxidation protein products.

The ozone treatment, in patients with diabetes type 2 suffering of neuroinfectious diabetic foot, improved glycemic control and prevented oxidative stress associated to diabetes mellitus and its complications, maintaining a cellular redox balance, in agreement with the excellent results obtained clinically in these patients.

Bocci, V., et al. (2014), An integrated medical treatment for type-2 diabetes, Diabetes and Metabolic Syndrome: Clilnical Research and Reviews, vol. 8, is. 1, pp. 57-61, doi: 10.1016/j.dsx.2013.10.004

This paper tries to emphasize two relevant concepts: the first is that type 2 diabetes is a chronic diseases characterized by both a dysmetabolism and a chronic oxidative stress. A variety of orthodox drugs are somewhat able to correct the metabolic alterations, but do not deal with the chronic inflammation. Consequently, as the validity of precisely treating blood with therapeutic ozone concentrations in restoring a redox homeostasis has been now demonstrated, the integration of ozone therapy appears essential for a rational treatment of type 2 diabetes. Such a combination may be able to reduce the diabetic epidemic.

Resistencia a la insulina

Bocci, V. (2011), Ozone. A new medical drug, 2nd. ed., Springer, Dordrecht, p. 182

Thus ozonetherapy not only improves the physiology of circulation, a well ascertained fact, but possibly enhances the insulin secretion and/or may decrease the resistance to insulin action. In other words, ozone therapy can turn a “vicious” into a “virtuous” circle.

Estabilización de la glucosa

Morejón, O., y cols. (2023), Aplicación de ozono por vía rectal a pacientes con diabetes mellitus, Revista Finlay, vol. 23, núm. 1, pp. 104-110

Fundamento: los pacientes con diabetes mellitus cursan con un aumento importante en el estrés oxidativo, donde hay una disminución en la actividad de los sistemas antioxidantes y un incremento de los productos de oxidación. El ozono actúa induciendo estrés oxidativo moderado y estimulando una defensa antioxidante enzimática. Objetivo: caracterizar el control metabólico de los pacientes diabéticos al inicio y al culminar la terapia con ozono rectal.

Métodos: se realizó un estudio cuasi experimental con pre y post terapia, donde el universo estuvo constituido por 121 pacientes diabéticos del consultorio médico de familia, número 15 del Policlínico Comunitario Docente José Luis Chaviano de Cienfuegos aplicándoles ozonoterapia por vía rectal previa evaluación médica, por 15 sesiones dos veces al año. Fueron recogidas como variables demográficas: edad y sexo; clínicas: parámetros hemoquímicos, tiempo de evolución de la enfermedad y estado nutricional; como complicaciones neurovasculares: pie diabético, polineuropatía diabética y retinopatía diabética; tratamientos: hipoglucemiantes; factores de riesgo modificables: hipertensión arterial, diabetes mellitus, tabaquismo, alcoholismo, realización de ejercicio físico; cálculo del índice de masa corporal. Los resultados hallados fueron expresados fundamentalmente mediante tablas y gráficos como principales recursos del lenguaje estadístico.

Resultados: los pacientes con diabetes mellitus tipo 2 predominaron con un 95,0 %. Existió una disminución de 2, 769 mmol/L de las cifras de glucemia después del tratamiento con ozono rectal lo que muestra un control metabólico.

Conclusiones: la ozonoterapia rectal puede ser utilizada como terapia complementaria al tratamiento convencional de pacientes con diabetes mellitus, pues mejora los parámetros de glucemia.

In Diabetes mellitus, long-term complications, that cause morbidity and premature mortality, are characterized by microvascular and macrovascular diseases…

Ozone has been used as a therapeutical agent and beneficial effects have been observed…

…ozone treatment improved glycemic control, and prevented oxidative stress, the increase of fructolysine content and advanced oxidation protein products.

Al-Dalain, S., et al. (2001), Ozone treatment reduces markers of oxidative and endothelial damage in an experimental diabetes model in rats, Pharmacological Research, vol. 44, no. 5, pp. 391-396, doi: 10.1006/phrs.2001.0867

Ozone has been used as a therapeutical agent and beneficial effects have been observed. However so far only a few biochemical and pharmacodynamic mechanisms have been elucidated. We demonstrate that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by reactive oxygen species (ROS). Taking into account that diabetes is a disorder associated with oxidative stress, we postulate that ozone treatment in our experimental conditions might protect antioxidant systems and maintain, at a physiological level, other markers of endothelial cell damage associated with diabetic complications. Five groups of rats were classified as follows: (1) control group treated only with physiological saline solution; (2) positive control group using streptozotocin (STZ) as a diabetes inductor; (3) ozone group, receiving 10 treatments (1.1 mg kg 1), one per day after STZ-induced diabetes; (4) oxygen group (26 mg kg 1), one per day, as in group 3 but using oxygen only; (5) control ozone group, as group 3, but without STZ. The ozone treatment improved glycemic control and prevented oxidative stress, the increase of aldose reductase, fructolysine content and advanced oxidation protein products. Nitrite and nitrate levels were maintained without changes with regard to non-diabetic control. The results of this study show that repeated administration of ozone in non-toxic doses might play a role in the control of diabetes and its complications.

Martínez, G., et al. (2005), Ozone treatment reduces blood oxidative stress and pancreas damage in a streptozotocin-induced diabetes model in rats, Acta Farmacéutica Bonaerense, vol. 24, núm. 4, pp. 491-497

In spite of the fact that ozone has been used as a therapeutical agent and beneficial effects have been observed, so far only a few biochemical and pharmacodynamic mechanisms have been studied. We have demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by Reactive Oxygen Species (ROS) through preservation of antioxidant endogenous systems. Taking into account that STZ produces ROS generation, which promotes pancreas damage with loss of its function, we studied ozone effects on blood oxidative stress and its relationship with pancreas injury mediated by STZ. Five groups of rats were classified as follows: (1) Non-diabetic control group treated only with citrate buffer solution; (2) positive control group using as a diabetes inductor; (3) Ozone group, receiving 10 treatments (1.1 mg/kg) one per day after STZinduced diabetes; (4 Ozone + STZ treatment improved glycemic control with regard to STZ group) Oxygen (26 mg/kg) one per day, as in group 3 but using oxygen only; (5) control ozone, as group 3, but without STZ. (16.1 ± 1.45 vs 27.12 ± 2.12 mmol/L). Blood oxidative stress was controlled by ozone as it was showed in the reduction of malondialdehyde, total hydroperoxides and peroxidation potential. In addition, antioxidant endogenous systems were increased (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione). In line with these results, there was a decrease in the percentage of damaged pancreatic islets by ozone treatment. Ozone antioxidant properties preserved β-cells functions and reduced hyperglycemia. Taken together, these results suggest that this complementary medical approach may represent a potential alternative in the treatment of diabetes and its complications.

Pie diabético

Dadfar, R., et al. (2023), Therapeutic utilization of zinc supplementation concurrent with ozone therapy ameliorates diabetic foot ulcer and attenuates serum level of c‑reactive protein‑ a case report study, Advanced Biomedical Research, vol. 12, no. 1, 3 p., doi: 10.4103/abr.abr_11_22

Non‑healing diabetic foot ulcer (DFU) is one of the main complications in diabetic patients. This case reported a 65-year-old male with a neuropathic ulcer in the right foot came to Ahwaz Wound Clinic after the wound had not healed with routine treatments. In addition to the routine treatment program, we used tropical ozone therapy and autohemotherapy (blood ozone therapy) for 2 months. Zinc supplementation (50 mg) was also administered daily during the treatment. The DFU was clearly healed with diminishing inflammation and wound closing, and there were no side effects. Additionally, the C‑reactive protein level was obviously decreased during the treatment indicating effective suppression of infection. This way indicates a helpful new intervention approach to the treatment of DFU.

Astasio-Picado, A., et al. (2023), Use of ozone therapy in diabetic foot ulcers, Journal of Personalized Medicine, vol. 13, no. 10, 1439, 14 p., doi: 10.3390/jpm13101439

Introduction: ozone therapy is a therapy composed of ozone. This gas is in the atmosphere with various general effects: direct disinfectant and trophic effects and a systemic antibacterial and antiviral effect. This gas also improves blood circulation, makes glucose metabolism more effective, improves erythrocyte metabolism, and improves fatty acid metabolism. Objective: Provide evidence of the effectiveness of ozone therapy in wounds of patients with diabetic foot. Analyze the effectiveness of ozone therapy compared to other treatments to achieve good wound healing in patients with diabetic foot. To study the benefits of the use of ozone therapy in ulcers of patients. Analyze the management of ozone therapy and other treatments to achieve healing of ulcers in patients. Methodology: A bibliographic review focused on articles published between November 2014 and June 2023 was carried out. The following databases were consulted: Pubmed (Medline), Dialnet, Google Scholar,Web of Science (WOS), Scielo, and Scopus. Results: After applying the article selection criteria and evaluating the quality of the methodology, a total of 17 articles were obtained. The results affirm ozone therapy as promising for the treatment of wounds in patients with diabetic foot. Conclusions: the evidence has been able to determine that ozone therapy is adequate for the treatment of diabetic foot ulcers. In addition, the therapy has been shown to be effective, safe, and beneficial, with few adverse effects for the treatment of diabetic foot ulcers.

Cardiovascular

Cheng, H., et al. (2025), A clinical study on ozone autohemotherapy for the treatment of acute ischemic stroke, Fontiers in Medicine, vol. 12, 10 p., doi: 10.4103/mgr.MEDGASRES-D-23-00013

Cardiovascular diseases (CVDs) represent a major concern for human health worldwide. Emergencies in this field include wide repertories of studies dealing primarily with CVD prevention. In addition to dietary habits and lifestyles, medical knowledge is fully needed to improve public educational programs toward cardiovascular risk factors and to enrich the endowment of pharmaceutical options and therapies to address CVDs, particularly for ischemic damage due to an impairment in the endothelial–myocardial relationship. Because ozone is a stimulator of the endothelial nitric oxide synthase/nitric oxide pathway, ozone therapy has been widely demonstrated to have the ability to counteract endothelial-cardiac disorders, providing a novel straightforward opportunity to reduce the impact of CVDs, including atrial fibrillation. In this review, we attempt to establish a state-of-the-art method for the use of ozone in CVD, suggesting that future remarks be addressed to provide fundamental insights into this issue. The purpose of this study was to highlight the role of ozone in the adjunctive medical treatment of cardiovascular pathologies such as acute myocardial infarction due to ischemic disorders.

Hipertensión

Dilshod, N. (2023), Ozone therapy in the treatment of patients with hypertension, Journal of Science in Medicine and Life, vol. 1, is. 4, pp. 135-141

CONCLUSION

1 The use of ozone in complex antihypertensive therapy increases the effectiveness of treatment in patients with hypertension: a more pronounced hypotensive effect during ozone therapy was observed during the daytime in patients with stage 1 P hypertension with normal body weight. The hypotensive effect of ozone therapy was accompanied by an increase in the number of patients with a favorable type of daily blood pressure profile dipper.

The use of ozone in complex antihypertensive therapy improves the electrophysiological properties of the myocardium and affects the autonomic regulation of the heart, which is expressed by a decrease in the incidence of late ventricular potentials and an increase in heart rate variability in patients with hypertension.
Antihypertensive therapy with the use of ozone is accompanied by positive dynamics of metabolic parameters: a decrease in the level of triglycerides, total cholesterol, VLDL, an increase in the level of HDL, antioxidant activity of blood serum and a decrease in the processes of lipid peroxidation in patients with hypertension.
Complex antihypertensive therapy using ozone improves the quality of life, reduces personal and reactive anxiety in patients with hypertension and has an aftereffect for three months.

Dilshod, N. (2023), Metabolic effects of ozone therapy in restorative treatment of patients with 1st degree arterial hypertension, Journal of Science in Medicine and Life, vol. 1, is. 4, pp. 117-120

The effect of ozone therapy on the metabolic status of patients with arterial hypertension was studied. Positive changes in metabolic parameters were noted in patients with arterial hypertension after a course of treatment with medical ozone. Ozone therapy helps normalize metabolic processes in most patients, lipid and carbohydrate metabolism, and reduces the risk of atherogenic changes in the body.

Ateroesclerosis

Makarov, I., et al. (2015), Complex non-drug treatment of obliterating atherosclerosis stage II by combined application medical ozone and gravity therapy. Randomized study, Stomatologiia (Mosk), vol. 23, no. 4, pp. 406-415, doi: 10.18484/2305-0047.2015.4.406

Objectives. Optimization of comprehensive treatment of patients with obliterating atherosclerosis (II stage) bycombined application of ozone and gravitational therapy.

Methods. A prospective randomized controlled study in three parallel groups in 139 patients has been performed. The first group (n=57) received standard medical therapy in combination with ozone therapy; the group was divided into two subgroups: in the subgroup 1a (n=28) the patients were given intravenous ozonated saline solution (OSS), in the subgroup 1b (n=29) – major ozonated autohemotherapy (MOAT). The patients of the second group (n=62) underwent the comprehensive treatment, including gravitational therapy (GT) in addition to medical ozone. In this group two subgroups were also identified: subgroup 2a (n=31) – the patients received standard medical therapy in combination with OSS and GT, subgroup 2b (n=31) – in combination with MOAT and GT. The third group, the control one (n=20), included patients received only standard medical therapy. The results were evaluated immediately prior and after the treatment according to pain-free walking distance, ankle-brachial index, lipid metabolism and lipid peroxidation processes.

Results. The highest efficiency was observed in the subgroup 2a. A statistically significant increase of painfree walking distance by 116,5%, ankle-brachial index – by 49,2% have been registered. The most pronounced positive dynamics of lipid metabolism has been observed: reduction of total cholesterol by 21,3%, low density lipoprotein – by 25,4%, very low density lipoprotein – by 24,2%, triglycerides – by 18,5%. The tendency towards normalization of lipid peroxidation was established: malondialdehyde decreased by 29,28%, the total antioxidant activity increased by 20,36%.

Conclusion. Combined application of ozonated physiological solution and gravity in the treatment of patients with obliterating atherosclerosis (stage II) contributes to a significant increase of pain-free walking distance and anklebrachial index; as will as a significant correction of violations of lipid metabolism and lipid peroxidation process.

Úlcera venosa

Pasek, J., et al. (2023), Topical hyperbaric oxygen therapy versus local ozone therapy in healing of venous leg ulcers, International Journal of Environmental Research and Public Health, vol. 20, no. 3, 1967, doi: 10.3390/ijerph20031967

Background: the treatment of venous leg ulcers still poses a difficult interdisciplinary medical problem. The aim of this study was to compare the therapeutic efficacy of local hyperbaric oxygen therapy with local ozone therapy in the treatment of venous leg ulcers. Materials: this study included 114 patients; 60 males (52.63%) and 54 females (47.36%) of ages ranging between 39 and 88 years (mean age: 68.9 9.8 years) with venous leg ulcers, who underwent topical hyperbaric oxygen therapy (group I) and local ozone therapy (group II). In each of the study groups, the patients underwent 30 therapeutic procedures lasting 30 min each. The progress in wound healing was evaluated by computerized planimetry, and the intensity of pain was assessed with the use of the Visual Analogue Scale (VAS). Results: in both groups of treated patients, a statistically significant (p = 0.000001) reduction in the area of treated ulcers was achieved. In group I, the wound área decreased by an average of 69.67 22.52%, from 7.55 2.99 cm2 to 2.78 2.43 cm2, and in group II, by an average of 41.33 21.31%, from 7.36 2.82 cm2 to 4.62 2.76 cm2. In both groups of patients, a statistically significant (p = 0.000001) reduction in the intensity of pain ailments was observed: in group I, by an average of 0.55 0.54 points, and in group II, by an average of 2.33 0.82 points on the VAS scale. Conclusions: local hyperbaric oxygen therapy and local ozone therapy cause a statistically significant reduction in the surface area of venous leg ulcers as well as in the intensity of pain. Better results were observed after the application of local hyperbaric oxygen therapy procedures.

Pasek, J., et al. (2023), Quality of life in patients with venous leg ulcers treated by means of local hyperbaric oxygen therapy or local ozone therapy—a single center study, Medicina, vol. 59, no. 12, 2071, 12 p., doi: 10.3390/medicina59122071

Abstract: Background and Objectives: Venous leg ulcers pose a significant medical problem worldwide. The complexity of the problem determines the need for further interdisciplinary activities that Will improve the quality of life for treated patients. This study compared the quality of life of patients with venous leg ulcers who received local hyperbaric oxygen therapy or local ozone therapy procedures as part of comprehensive treatment. Materials and Methods: The study included 129 patients (62 men and 57 women) with venous leg ulcers. Group I underwent local hyperbaric oxygen therapy (HBOT), and Group II underwent local ozone therapy (OZONE). In both groups, the patients’ quality of life was assessed before the start of the treatment cycle, as well as 10 weeks and 6 months after the completion of the treatment, by means of the EQ-5D-5L questionnaire and the Polish shortened version of the SF- 36 scale. Results: After completing the respective therapeutic cycle, both groups showed statistically significant (p < 0.001) improvement in quality of life, according to the EQ-5D-5L questionnaire and the SF-36 scale. Differences were noted between the 1st examination (before treatment) and the 2nd examination (10 weeks after treatment), as well as the 3rd examination (6 months after treatment). In the EQ-5D-5L assessment of anxiety and depression, self-care, and activities of daily living 6 months after the end of treatment, better results were found in the group of patients treated with local hyperbaric oxygen therapy (p < 0.001). In this group, 6 months after the end of the treatment, a statistically significantly higher result on the EQ-VAS scale was also obtained (73.09 _ 19.8 points vs. 68.03 _ 17.37 points, p = 0.043). However, in the SF-36 assessment performed 6 months after the end of treatment, better results—a statistically significantly lower value of the quality of life index—were recorded in the group of patients treated with local ozone therapy (103.13 _ 15.76 points vs. 109.89 _ 15.42 points, p < 0.015). Conclusions: Hyperbaric oxygen therapy and local ozone therapy procedures have a beneficial effect on improving the quality of life of patients with venous leg ulcers.

Heridas

Romary, D., et al. (2023), Liquid ozone therapies for the treatment of epithelial wounds: a systematic review and meta-analysis, International Wound Journal, vol. 20, no. 4, pp. 1235-1252, doi: 10.1111/iwj.13941

Ozonated water and ozonated oils are emerging as potential therapies for wound care, but their efficacy has not been appropriately evaluated. The aim of this systematic review and meta-analysis was to evaluate the therapeutic potential of topical ozone in the treatment of mammalian wounds. A structured search of five scientific databases returned a total of 390 unique studies. Of these, 22 studies were included in this review. Four studies provided enough data to be included in a meta-analysis evaluating the time to complete wound healing. All studies were randomised controlled trials of humans or other mammalian animals that reported clinical signs of wound healing. Each study was critically analysed by a six-point assessment of the risk of bias. Wounds treated with topical ozone had a greater reduction in wound size than similar wounds treated with controls or standard of care in all studies. Those treated with ozonated liquids also had a horter time to wound healing by approximately one week. In conclusion, topical ozone contributed to enhanced wound healing in all studies. While additional human experiments would be helpful to quantify ozone’s specific effects on wound healing compared to standard treatment, topical ozone should be considered as part of an overall wound management strategy.

Heridas postquirúrgicas

Varghese, L., et aol. (2023), Effectiveness of topical ozone gel application in the management of postextraction wound healing: an in vivo study, The Journal of Contemporary Dental Practice, vol. 24, no. 11, pp. 887-890, doi: 10.5005/jp-journals-10024-3557

Aim: The purpose of the current study was to determine the effectiveness of topical ozone gel application in the management of postextraction wound healing.

Materials and methods: The current study involved a total of 40 participants. The patients were randomly placed into two groups with sample size estimated as n = 20 in each group. Group A: Control: patients received only saline irrigation and group B: patients receiving topical ozone gel. The surgical procedure was standardized for all groups, and local anesthesia was used during the procedure. After the removal of the mandibular third molar, the control group irrigated the socket with saline, whereas in the study group, the socket was filled with ozone gel. On the first, third, fifth, and seventh postoperative days, a single examiner evaluated each participant for postoperative mouth opening, discomfort, and patient satisfaction. The t-test was used to analyze quantitative data, whereas the Fisher exact test was employed to analyze qualitative data. Statistical significance was defined as a p value less than 0.05.

Results: On comparison of patient satisfaction, in the ozone gel group, 13 patients were very satisfied but in the control group, 8 patients were very satisfied. On comparison of pain intensity, on the 5th day, the complete absence of pain patients was more in the ozone gel group (12 patients) compared with the control group (4 patients). There was a statistically significant difference found between these two groups (p < 0.001). On comparison of mouth opening, on the 3rd and 5th day, mouth opening was better in the ozone gel group (29.22 ± 1.28 and 34.06 ± 0.09) compared with the control group (27.38 ± 1.03 and 31.14 ± 0.82), respectively. And there was a statistically significant difference found between these two groups (p < 0.001) on both the days.

Conclusion: The current study came to the conclusion that using ozone gel significantly improves postoperative pain, mouth opening range, and promotes faster wound healing.

Clinical significance: The primary goals of postoperative care for exodontia patients have always been pain management and infection control. The most frequent postoperative consequences are pain and edema. Hence, ozone therapy can be used as an effective topical agent to manage postextraction pain and swelling in healthy patients without the need for excess medications.

Palma, L., et al. (2023), Effects of ozone therapy on periodontal and peri-implant surgical wound healing: a systematic review, Quintessence International, 2023, vol. 54, no 2, pp. 100-110, doi: 10.3290/j.qi.b3512007

Objective: To evaluate the effectiveness of the use of adjuvant ozone therapy in the healing process of wounds resulting from periodontal and peri-implant surgical procedures by answering the following focused question: “Can adjuvant ozone therapy improve wound healing outcomes related to periodontal and peri-implant surgical procedures?”. Method and materials: MEDLINE (via PubMed), EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched, without language restriction, for peer-reviewed articles published until 23 March 2022, in addition to manual search. Only controlled clinical trials (randomized or not) were considered. The risk of bias was evaluated by the Cochrane risk-of-bias tool for RCTs – version 1 (RoB1). Data were pooled into evidence tables and a descriptive summary was presented. Results: Of the 107 potentially eligible records, only seven studies were included. Four addressed free/deepithelialized gingival grafts with a palatal donor area, two evaluated implant sites, and one comprised gingivectomy and gingivoplasty. A total of 225 patients were evaluated in the included studies, considering control and test groups (ozone and other adjuvant therapies for comparison). Ozone therapy had a positive effect on outcomes directly or indirectly related to periodontal/peri-implant surgical wound healing. Furthermore, it could also increase the stability of immediately loaded single implants installed in the posterior mandible. Conclusion: In general, ozone therapy seems to both accelerate the healing processes of periodontal/peri-implant wounds and increase the secondary stability of dental implants; however, considering the limited evidence available and the risk of bias in the included studies (none classified as low risk), a definitive conclusion cannot be drawn.

Heridas crónicas

Ozturk, G., and B. Kocyigit (2023), Healing refractory livedoid vasculopathy-related skin ulcers by ozone therapy: a case-based review, Rheumatology International, vol. 44, no. 2, pp. 369-377, doi: 10.1007/s00296-023-05504-1

Chronic skin wounds represent a prominent etiological factor in the occurrence of non-traumatic foot amputations on a global scale and pose a substantial threat to the patient’s well-being and mortality in the absence of effective treatment strategies. There exists a subset of patients that exhibit an insufficient response to different treatment options, comprising antibiotics, dressings, gauze bandages, debridement, rehabilitation, collagen patch, and vacuum-assisted closure. In this patient group, distinct treatment strategies emerge before surgery and amputation. Ozone therapy is one of them. Ozone exhibits a wide variety of effects such as antimicrobial, anti-inflammatory, antioxidant, and trophic. Its trophic effect is mediated by disinfection, stimulation of granulation tissue, acceleration of the angiogenesis process, and detoxification mechanisms. In this article, we presented the beneficial effect of ozone therapy in a case of chronic skin ulcer associated with livedoid vasculopathy. In this context, we aimed to discuss the role of ozone therapy in the management of chronic skin ulcers. Finally, we focused on ozone therapy as a promising method in inflammatory rheumatic diseases.

Infección cutánea

Roth, A., et al. (2023), Ozone as a topical treatment for infected dermal wounds, Frontiers in Bioscience (Elite ed), vol. 15, is. 2, 9, 20 p., doi: 10.31083/j.fbe1502009

Dermal wound infections are a rising source of morbidity and mortality in patients worldwide as new and worsening complications reduce the efficacy of traditional treatments. These challenges in wound care are increasingly caused by comorbidities such as obesity and diabetes as well as surging rates of antibiotic resistance. As a result, there is an urgent need for alternative treatment options. Gaseous ozone has shown great promise as a potential new treatment for infected dermal wounds. In this brief review of current wound therapy techniques found in the literature, an in-depth discussion of the mechanisms, benefits, and results of topical ozone gas as a therapy for infected dermal wounds is presented. This includes studies of ozone applied to wounds performed in vitro, in vivo, and clinical settings, as well as the use of ozone as an adjunct therapy for increasing the efficacy of traditional treatments. The overwhelming evidence suggests that ozone exhibits significant antimicrobial properties and has been shown to promote wound healing factors, especially when applied between 5–60 ppm. As such, this promising alternative therapy warrants a significant investment of time and resources to fully utilize ozone as an effective treatment against antibiotic resistant bacteria and other rising challenges in wound treatment.

Roth, A. et al. (2023), Biocompatibility and safety assessment of combined topical ozone and antibiotics for treatment of infected wounds, ACS Biomaterials Science & Engineering, vol. 9, no. 6, pp. 3606–3617, doi: 10.1021/acsbiomaterials.2c01548

Wound infections with antibiotic-resistant bacteria, particularly the Gram-negative strains, pose a substantial health risk for patients with limited treatment options. Recently topical administration of gaseous ozone and its combination with antibiotics through portable systems has been demonstrated to be a promising approach to eradicate commonly found Gram-negative strains of bacteria in wound infections. However, despite the significant impact of ozone in treating the growing number of antibiotic-resistant infections, uncontrolled and high concentrations of ozone can cause damage to the surrounding tissue. Hence, before such treatments could advance into clinical usage, it is paramount to identify appropriate levels of topical ozone that are effective in treating bacterial infections and safe for use in topical administration. To address this concern, we have conducted a series of in vivo studies to evaluate the efficacy and safety of a portable and wearable adjunct ozone and antibiotic wound therapy system. The concurrent ozone and antibiotics are applied through a wound interfaced gas permeable dressing coated with water-soluble nanofibers containing vancomycin and linezolid (traditionally used to treat Gram-positive infections) and connected to a portable ozone delivery system. The bactericidal properties of the combination therapy were evaluated on an ex vivo wound model infected with Pseudomonas aeruginosa, a common Gram-negative strain of bacteria found in many skin infections with high resistance to a wide range of currently available antibiotics. The results indicated that the optimized combination delivery of ozone (4 mg h–1) and topical antibiotic (200 μg cm–2) provided complete bacteria eradication after 6 h of treatment while having minimum cytotoxicity to human fibroblast cells. Furthermore, in vivo local and systemic toxicity studies (e.g., skin monitoring, skin histopathology, and blood analysis) on pig models showed no signs of adverse effects of ozone and antibiotic combination therapy even after 5 days of continuous administration. The confirmed efficacy and biosafety profile of the adjunct ozone and antibiotic therapy places it as a strong candidate for treating wound infection with antimicrobial-resistant bacteria and further pursuing human clinical trials.

Astuti, S., et al. (2023), Effectiveness of ozone-laser photodynamic combination therapy for healing wounds infected with methicillin-resistant staphylococcus aureus in mice, Veterinary World, vol. 16, no. 5, pp. 1176-1184, doi: 10.14202/vetworld.2023.1176-1184

Background and Aim: According to 2013 data from the Ministry of Health of the Republic of Indonesia, there were 8.2% more wounds than typical in Indonesia; 25.4% were open wounds, 70.9% were abrasions and bruises, and 23.2% were lacerations. A wound is defined as damage or loss of body tissue. This study aimed to determine the effectiveness of wound healing using red-laser therapy (650 nm, 3.5 J/cm2), blue-laser therapy (405 nm, 3.5 J/ cm2), ozone therapy, red-laser therapy (650 nm, 3.5 J/cm2) with ozone, and blue-laser therapy (405 nm, 3.5 J/cm2) with ozone.

Materials and Methods: One hundred and twelve mice were given incision wounds and infected with methicillin-resistant Staphylococcus aureus (MRSA). The study used a factorial design with two factors: The type of therapy (n = 7) and irradiation time (days 1, 2, 4, and 6). The mice were divided into seven therapy groups: Control group with NaCl, control with Sofra-tulle® treatment, red-laser therapy (650 nm, 3.5 J/cm2), blue-laser therapy (405 nm, 3.5 J/cm2), ozone therapy, red-laser therapy (650 nm, 3.5 J/cm2) with ozone, and blue-laser therapy (405 nm, 3.5 J/cm2) with ozone. This therapy was performed using irradiation perpendicular to the wound area. The photosensitizer used was curcumin 10 mg/mL, which was applied to the wound area before exposure to a laser and ozone. The ozone oncentration was 0.011 mg/L with a flow time of 80 s. The test parameters were the number of collagens, bacterial colonies, lymphocytes, monocytes, and wound length measurement to determine their acceleration effects on wound healing. Data were analyzed by a two-way (factorial) analysis of variance test.

Results: Acceleration of wound healing was significantly different between treatments with a laser or a laser-ozone combination and treatment using 95% sodium chloride (NaCl) and Sofra-tulle®. On day 6, the blue-laser with ozone treatment group had efficiently increased the number of bacteria and reduced the wound length, and the red-laser treatment with ozone increased the amount of collagen. In addition, the red-laser also reduced the number of lymphocytes and monocytes, which can have an impact on accelerating wound healing. Blue-laser therapy was very effective for increasing the number of epithelia.

Conclusion: The blue- and red-laser combined with ozone treatments effectively accelerated the healing of incisional wounds infected with MRSA bacteria.

Respiratorio

Asma

Turrent, J. y S. Menéndez (1998), Ozonoterapia en el asma bronquial: bases terapéuticas para su aplicación, Revista CENIC Ciencias Biológicas, vol. 29, núm. 3, pp. 161-164

El asma bronquial es una afección que acapara la atención de amplios sectores de todo el mundo por la alta incidencia de muertes que ocasiona y por los elevados costos hospitalarios que su atención demanda. El ozono es reconocido como un potente agente oxidante capaz de producir efectos adversos cuando es inhalado, y ha sido asociado con la incidencia de crisis asmáticas. Por otra parte, es conocido que cuando el ozono se aplica en dosis adecuadas y por una vía no dañina para el organismo produce variadas acciones biológicas con efectos terapéuticos sin causar reacciones adversas ni daño genotóxico, lo que hace posible su empleo en una gran variedad de procesos patológicos. Existen referencias acerca del empleo de la ozonoterapia en el asma bronquial aunque no se fundamentan los mecanismos fisiológicos mediante los cuales el método propuesto ejerce su acción terapéutica en dicha enfermedad. El presente trabajo pretende explicar los probables mecanismos de acción a través de los cuales la ozonoterapia puede ser efectiva como método terapéutico en el asma bronquial.

EPOC

Calunga, J., y cols. (2011), La ozonoterapia en pacientes con enfisema pulmonar, Revista Médica de Chile, vol. 139, no. 4, pp. 439-447, doi: 10.4067/S0034-98872011000400004

La enfermedad pulmonar obstructiva crónica (EPOc) se caracteriza por limitación progresiva al flujo del aire, no totalmente reversible, asociada con una respuesta inflamatoria anormal a partículas o gases nocivos. clásicamente se identifican dos fenotipos: pacientes con EPOc en los que predomina la destrucción –enfisema– o bien, el caso de pacientes que predomina la obstrucción bronquial bronquitis crónica.

Background: Ozone therapy may stimulate antioxidant systems and protect against free radicals. It has not been used formerly in patients with pulmonary emphysema. Aim: To assess the effects of rectal ozone therapy in patients with pul-monary emphysema. Material and Methods: Sixty four patients with pulmonary emphysema, aged between 40 and 69 years, were randomly assigned to receive rectal ozone in 20 daily sessions, rectal medicinal oxygen or no treatment. Treatments were repeated three months later in the frst two groups. At baseline and at the end of the study, spirometry and a clinical assessment were performed. Results: fifty patients completed the protocol, 20 receiving ozone therapy, 20 receiving rectal oxygen and 10 not receiving any therapy. At baseline, patients on ozone therapy had significantly lower values of forced expiratory volume in the frst second (fEV₁) and fEV₁/forced vital capacity. At the end of the treatment period, these parameters were similar in the three treatment groups, therefore they only improved significantly in the group on ozone therapy. No differences were observed in other spirometric parameters. Conclusions: Rectal ozone therapy may be useful in patients with pulmonary emphysema.

Neumonía

Izadi, M., et al. (2021), Ozone therapy for the treatment of COVID-19 pneumonia: a scoping review, International Immunopharmacology, vol. 92, 107307, doi: 10.1016/j.intimp.2020.107307

Severe forms of COVID-19 can evolve into pneumonia, featured by acute respiratory failure due to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In viral diseases, the replication of viruses is seemingly stimulated by an imbalance between pro-oxidant and antioxidant activity as well as by the deprivation of antioxidant mechanisms. In COVID-19 pneumonia, oxidative stress also appears to be highly detrimental to lung tissues. Although inhaling ozone (O3) gas has been shown to be toxic to the lungs, recent evidence suggests that its administration via appropriate routes and at small doses can paradoxically induce an adaptive reaction capable of decreasing the endogenous oxidative stress. Ozone therapy is recommended to counter the disruptive effects of severe COVID-19 on lung tissues, especially if administered in early stages of the disease, thereby preventing the progression to ARDS.

Rinitis alérgica

Schwartz, A., et al. (2011), Guía para el uso médico del ozono. Fundamentos terapéuticos e indicaciones, Madrid, España, pp. 228-229.

15.4 Rinitis

15.4.1 Rinitis aguda

La rinitis aguda también puede deberse a la influencia del polvo, el humo, los vapores de diferentes ácidos y otras sustancias.

En la evolución de la enfermedad se diferencian tres estadios. El primero de ellos, la inflamación de la mucosa nasal y nasofaríngea, adura 1-2 días. El segundo estadio, la secreción reforzada, con abundante secreción nasal, serosa y mucosa, se prolonga durante casi un día. En el tercer estadio, las secreciones adquieren un carácter mucopurulento y los síntomas de la enfermedad empiezan a debilitarse. Al cabo de 7-10 días se alcanza la curación.

El tratamiento local se dirige a eliminar las dificultades en la respiración nasal y disminuir los fenómenos inflamatorios. La ozonoterapia resulta adecuada en la segunda fase.

Enfermedades respiratorias crónicas

Khmeleva, E., et al. (2012), Medical applications of ozone for the rehabilitation of the patients presenting with chronic bronchitis and arterial hypertension, Voprosi Kurortologii, Fizioterapii, i Lechebnoi Fiziochescoi Kultury, vol. 3, pp. 3-8

Of paramount importance at the stage of rehabilitative treatment of the patients presenting with combined cardiorespiratory pathology are therapeutic measures aimed at eliminating the principal components of pathogenesis of a given disease and correcting the concomitant immunometabolic disturbances. Our investigations have demonstrated that ozone therapy given to the patients with chronic bronchitis and hypertension produces lipid-lowering, hypoglycemic and fibrinolytic effects. Its combination with anti-hypoxic treatment helps to normalize the functioning capabilities of all organs and systems of the body. Immunomodulatory effects of ozone therapy is attributable to the disintoxicative and anti-hypoxic actions of medical ozone as well as activation of the “lipid peroxidation–antioxidant protection” system.

Dobkin, V., et al. (2001), Local ozone therapy in the complex surgical reatment of pulmonary and pleural tuberculosis patients, Problemy Tuberkuleza, vol. 2001, no. 7, pp. 18-20

The found bactericidal activity of ozone and oxygen mixture containing ozone, 10 mg/l, and ozoned solutions of furacilin (dilution 1:5000) and chlorohexidine (0.05%) against the nonspecific microflora and Mycobacteria tuberculosis allowed them to be used in the treatment of 55 patients with pleural empyema. Analyzing the outcomes of treatment in these patients versus 59 matched patients indicated that local ozone therapy accelerated sanitation and stimulation of reparative processes in this disease on the average by a fortnight. Local ozone therapy used in the preoperative preparation of patients with pulmonary tuberculosis and pleural empyema reduced the number of purulent postoperative complication to 17.7% versus 30.4% in the controls, enhanced the efficiency of multimodality treatment by 15.6% and reduced mortality by 9.5%. Analyzing the results of prevention of purulent bronchopleural complications after pleuropulmonectomy in 31 patients in the experimental group and in 35 in the control one showed that with local ozone therapy, complications occurred in 16.1 and 28.6%, respectively, and the efficiency of surgical management increased by 13.1% and mortality rates reduced by 9.6%.

Belianin, I. and R Iu Abdullaev (2000), Use of soluble ozone in combined treatment of pulmonary tuberculosis: lipid peroxidation and blood antioxidative defense systems, Problemy Tuberkuleza, vol. 2000, no. 3, pp. 41-44

Changes in lipid peroxidation and blood antioxidative defense systems and red blood cell function were studied in 16 patients with prolonged progressive pulmonary tuberculosis in response to intravenous soluble ozone (SO) administration. There was a drastic rise in the activity of intraerythrocytic superoxide dismutase (SOD) and a reduction in intracellular malonic dialdehyde (MDA) levels. In the remaining patients, there was a decrease in the activity of SOD and an increase in intraerythrocytic MDA concentrations. Plasma catalase activity increased in all patients and MDA levels lowered. It is proposed that initial SO doses for patients with chronic pulmonary tuberculosis should be chosen on an individual basis by taking into account intraerythrocytic SOD-MDA changes due to SO initiation.

Covid 19

Aghamohammadi, D., et al. (2024), Effects of adjuvant ozone autohemotherapy combined with routine treatment on clinical and paraclinical features of mechanically ventilated COVID-19 patients in the intensive care unit: a pilot randomized controlled trial, Medical Gas Research, vol. 14, no. 2, pp. 67-74, doi: 10.4103/2045-9912.385439

Until the availability of an effective and practical vaccine, there is a serious need to recognize alternative treatments for coronavirus disease 2019 (COVID-19). This study aimed to determine whether major ozonated autohemotherapy (MOAH) can improve the clinical and paraclinical parameters in critically-ill patients with COVID-19 requiring mechanical ventilation. In this controlled trial, we enrolled 40 critically ill COVID-19 patients receiving invasive mechanical ventilation. The enrolled patients were then randomized into the MOAH and control groups. The patients in the MOAH group received MOAH three times per week (10 times in total) in addition to routine treatment and standard critical supportive care. Patients in the control group were only given regular treatment and standard critical supportive care. The patients in the MOAH group had more days of breathing with no aid than those in the control group. Moreover, the length of stay in the intensive-care unit was significantly lower in the MOAH group than in the control group. MOAH resulted in higher ventilation-free days and less intensive-care unit stay compared with the control treatment. In COVID-19 patients undergoing mechanical ventilation, MOAH with routine treatment resulted in more ventilator-free days and less intensive-care unit stay compared with the standard therapy.

Shang, W., et al. (2022), Benefits of ozone on mortality in patients with COVID-19: A systematic review and meta-analysis, Complementary Therapies in Medicine, vol. 72, p. 102907, doi: 10.1016/j.ctim.2022.102907

Background: The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. Ozone therapy has long been used in the treatment of a valiety of infectious diseases, probably through its antioxidant properties and the supply of oxygen to hypoxic tissues. This systematic review and meta-analysis aimed to determine the efficacy of ozone on mortality in pa tients with COVID-19.

Methods: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Prospective controlled trials on treatment of COVID-19 with ozone, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs) and weighted mean differences (WMDs), with 95% confidence inte1vals (Cls).

Results: Eight trials (enrolling 371 participants) met the inclusion criteria. Ozone therapy showed significant effects on mortality (RR 0.38, 95% Cl 0.17-0.85; P = 0.02), length of hospital stay (WMD – 1.63 days, 95% Cl – 3.05 to – 0.22 days; P = 0.02), and polymerase chain reaction (PCR) positivity (RR 0.07, 95% Cl 0.01-0.34; P = 0.001 ).

Conclusions: Ozone therapy significantly reduced mortality, PCR positivity, and length of stay in hospitalized patients with COVID-19. Ozone therapy should be considered for COVID-19 patients.

Haraplan, B., and T. Harapan (2023), The role of ozone therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) a review, Medical Gas Research, vol. 13, no. 4, pp. 165-171, doi: 10.4103/2045-9912.369237

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.

Gadelha, M., et al. (2023), Clinical effectiveness of medical ozone therapy in COVID-19: the evidence and gaps map, Medical Gas Research, vol. 13, no. 4, pp. 172-180, doi: 10.4103/2045-9912.372819

Ozone therapy (OT), a medical procedure, has been showing good results during the coronavirus disease (COVID-19). We aimed to build an evidence and gaps map (EGM) of OT in the COVID-19 ranking the articles found according to levels of evidence and outcomes. The EGM brings bubbles of different sizes and different colors according to the articles. The OT intervention used was major or minor autohemotherapy, rectal insufflation and ozonized saline solution. EGM was based on 13 clinical studies using OT for COVID-19 involving a total of 271 patients. We found 30 outcomes related to OT in COVID-19. Our EGM divided the outcomes into six groups: 1-clinical improvement; 2-hospitalization; 3-inflammatory, thromboembolic, infectious, or metabolic markers; 4-radiological aspects, 5-viral infection and 6-adverse events. Major autohemotherapy was present in 19 outcomes, followed by rectal insufflation. Improvement in clinical symptoms of COVID-19, improvement of respiratory function, improvement of oxygen saturation, reduction in hospital internment, decrease in C-reactive protein, decrease in ferritin, decrease in lactate dehydrogenase, decrease in interleukin 6, decrease in D-dimer, radiological improvement of lung lesions and absence of reported adverse events were related in the papers. The most commonly used concentrations of OT in major autohemotherapy and in rectal insufflation were 40 μg/mL and 35 μg/mL, respectively. Here, we bring the first EGM showing the efficacy and safety of OT in the treatment of COVID-19. OT can be used as integrative medical therapy in COVID-19 at a low cost and improve the health conditions of the patients.

Ortopedia / dolor

Li, X., et al. (2024), Ozonated autohemotherapy combined with pulsed radiofrequency in the treatment of thoracic postherpetic neuralgia in older adults: a retrospective study, Medical Gas Research, vol. 14, no. 1, pp. 12-18, doi: 10.4103/2045-9912.372666

Postherpetic neuralgia (PHN) seriously affects the quality of life of the elderly population. This study aimed to evaluate the efficacy of ozonated autohemotherapy (O3-AHT) combined with pulsed radiofrequency (PRF) in the treatment of thoracic PHN in older adults. The medical records of patients with thoracic PHN aged 65 years and older from June 2018 until March 2021 in Shengli Oilfield Central Hospital were reviewed. They were assigned into two groups: PRF alone (PRF group, n = 107) and PRF combined with O3-AHT (PRF + O3-AHT group, n = 109). Visual Analogue Scale for pain was evaluated at pre-treatment, 1 day, 1, 3 and 6 months after treatment. Quality of life and sleep quality were assessed using Short-Form 36 Health Survey and Athens Insomnia Scale at pre-treatment and 6 months post-treatment, respectively. The median age of patients in the PRF and PRF + O3-AHT groups were 69 (67–73) years and 68 (67–72) years, respectively. The former included 62 females and the latter included 51 females. Compared with pre-treatment, the Visual Analogue Scale scores of two groups declined at post-treatment. Patients in the PRF + O3-AHT group showed obviously lower Visual Analogue Scale scores compared with those in the PRF group at 1, 3, and 6 months after treatment and they had earlier withdrawal time for drugs. However, dizziness, tachycardia, sleepiness, and nausea were presented after combination therapy. These symptoms resolved spontaneously after a period of rest. Additionally, O3-AHT combined with PRF was associated with a significant decrease in the Athens Insomnia Scale score and with a significant improvement in every dimension of the Short-Form 36 Health Survey. To conclude, O3-AHT combined with PRF is an effective way to relieve thoracic PHN in older patients.

Wang, X., et al. (2023), The effect of CT-guided pulsed radiofrequency combined with ozone injection on zoster-associated pain: a retrospective study, Journal of Pain Research, vol. 16, pp. 1321-1332, doi: 10.2147/jpr.s398578

Purpose: Globally, the incidence of herpes zoster (HZ) is increasing, and the resulting zoster-associated pain (ZAP) severely affects the quality of life of patients. Therefore, active treatment of ZAP and prevention of postherpetic neuralgia (PHN) are very important for patients in the early stage of the disease. This retrospective observational study aimed to evaluate the effect of CT-guided pulsed radiofrequency (PRF) combined with ozone injection on zoster-associated pain.

Patients and Methods: From 2018 to 2020, 84 patients with AHN (n=28), SHN (n=32), or PHN (n=24) underwent PRF combined with ozone injection treatment after pharmacologic and conservative therapies failed. The visual analogue scale (VAS), the Pittsburgh Sleep Quality Index (PSQI), and pregabalin consumption were recorded at baseline, post-PRF, and at 1, 3, 6, and 12 months after treatment. The number of remediations performed and adverse reactions were recorded, and treatment inefficiency was calculated using a VAS score greater than 3 as the criterion.

Results: The pooled results demonstrated statistically significant decreases in VAS scores, PSQI scores and consumption of pregabalin post-PRF and at 1, 3, 6, and 12 months follow-up (P<0.05). Compared with the PHN group, both the AHN and SHN groups showed clinical and statistical improvement in VAS scores and PSQI scores and in consumption of pregabalin (P< 0.05). At 1 year after the operation, the PHN group had a significantly greater number of remediation events and greater treatment inefficiency than the other two groups. No serious adverse events were observed during the procedure or during the follow-up period.

Conclusion: CT-guided PRF combined with ozone injection is safe and effective for individuals with ZAP, and its short-term and long-term effects are significant. In a sense, early PRF combined with ozone injection is more effective.

Yang, J., et al. (2023), Clinical efficacy and metabolomic analysis of ozone major autohemotherapy for the treatment of herpes zoster, Advances in Dermatology and Allergology, vol. 40, no. 5, pp. 693-698, doi: 10.5114/ada.2023.130522

Introduction: It is essential to understand the underlying changes in the patients’ metabolic profiles that may be indicative of the therapy’s effectiveness.

Aim: To prospectively analyse the clinical efficacy of ozone autohemotherapy in the treatment of acute herpes zoster and investigate its impact on serum metabolomics.

Material and methods: A total of 76 patients with acute herpes zoster between May 2018 and June 2020 were enrolled and divided into an experimental group and a control group. The pain location, Numeric Rating Scale (NRS) scores before and after treatment (1 week, 1 month, 3 months, and 6 months post-treatment), medication usage, and Quality of Sleep (QS) scores were prospectively analysed. Additionally, serum metabolomic data were obtained and analysed before and 6 months after the treatment.

Results: There were statistically significant differences in the total NRS scores before and after ozone autohemotherapy (p < 0.05). The NRS scores of both groups significantly decreased (p < 0.05). At the 6-month follow-up, no patients were lost, and 83 patients completed the follow-up. The NRS improvement at 1 week, 1 month, 3 months, and 6 months post-treatment in the experimental group was significantly lower than that in the control group (p < 0.05). There was no significant difference in the medication usage (pregabalin or tramadol sustained-release tablets) between the two groups (p > 0.05). One month after treatment, the QS score improvement in the diabetes group was significantly lower than that in the non-diabetes group (p < 0.05). Serum metabolomics analysis revealed three significantly decreased metabolites, namely creatine, adipate, and glucose, after treatment.

Conclusions: Ozone autohemotherapy is an effective treatment for acute herpes zoster patients and can rapidly and effectively alleviate pain symptoms in the short term. The changes in serum metabolomics may provide further insights into the treatment mechanism.

Artrosis (cadera/rodilla)

Borroto, V., y cols. (2016), Campos electromagnéticos pulsados y ozono en el tratamiento de artrosis de rodilla en el adulto mayor, Revista Española de Ozonoterapia, vol. 6, núm. 1, pp. 27-39

Objetivo: Evaluar el efecto de Campos electromagnéticos pulsados para el tratamiento de la artrosis de rodilla y la combinación de estos con infiltraciones intrarticulares de ozono en el adulto mayor.

Método: Se realizó un estudio, prospectivo, longitudinal en 90 pacientes mayores de 60 años de edad, con diagnóstico clínico y radiológico de artrosis de la rodilla grado II y III rebelde al tratamiento médico, que acudieron a la consulta de ozonoterapia del Policlínico Rampa en el periodo de enero a diciembre de 2014. Se dividió la muestra en tres grupos de 30 pacientes cada uno: 1) AINES, es el control, se les aplicó antiinflamatorios no esteroideos 2) Se les aplicó 10 sesiones de terapia con frecuencias electromagnéticas pulsadas (PEMF) tres veces por semana 3). Se les aplicó 10 sesiones de PEMF tres veces por semana igual que en el grupo 2 más 10 infiltraciones intrarticulares con ozono con una frecuencia de tres veces por semana. Todos los resultados se evaluaron antes y después del tratamiento. Se evaluó el dolor percibido mediante la escala visual analógica del dolor (EVA), la funcionalidad mediante la administración del cuestionario WOMAC (The Western Ontario and McMaster Universities Osteoarthritis Index), el grado de mejoría clínica, la cantidad mínima de aplicaciones con las que se logra la mejoría y la incidencia de eventos adversos.

Resultados: El protocolo utilizado con terapia PEMF para la artrosis de rodilla fue muy superior a la aplicación de AINES con una diferencia estadísticamente significativa (p=0,00) y los resultados fueron aún mejores cuando se combinaron con las infiltraciones intrarticulares con ozono. En los grupos tratados con ozono y con frecuencias electromagnéticas pulsadas no se reportaron eventos adversos, con la aplicación de AINES se presentaron eventos adversos gastrointestinales y tensión arterial alta.

Conclusiones: El tratamiento con campos electromagnéticos pulsados para la artrosis de rodilla grado II y III es un método seguro y efectivo y se potencializa su acción cuando se combina con infiltraciones intraarticulares con ozono.

Borroto, V., y cols. (2013), Ozonopuntura en el tratamiento de la artrosis de rodilla, Revista Cubana de Medicina Física y Rehabilitación, vol. 5, núm. 1, pp. 43-54

Objetivo: determinar el efecto de la combinación de la infiltración intrarticular de ozono combinado con ozonopuntura para el tratamiento de la artrosis de rodilla.

Métodos: se realizó un estudio aleatorizado, prospectivo, longitudinal en 60 pacientes mayores de 55 años de edad, con diagnostico clínico y radiológico de artrosis de la rodilla, que acudieron al Servicio de Calidad de Vida del Centro Nacional de Medicina Natural y Tradicional en el periodo comprendido desde enero de 2009 a enero de 2010. Se dividió la muestra en tres grupos: 1) Control, se aplicó antinflamatorios no esteroideos. 2) Se aplicaron 15 infiltraciones intrarticulares con ozono dos veces por semana. 3) Se aplicaron 15 sesiones de ozonopuntura en las rodillas, además del tratamiento utilizado con el Grupo 2. Se evaluaron antes, después, y a los seis meses de concluido el tratamiento, se evaluaron las variables siguientes: el grado de mejoría clínica, la cantidad mínima de aplicaciones con que se logra la mejoría, la incidencia de eventos adversos.

Resultados: el grupo tratado solo con infiltraciones intrarticulares de ozono y el tratado con infiltraciones con ozono intrarticulares más en puntos de acupuntura, fueron estadísticamente superiores a los del grupo tratado con antinflamatorios no esteroideo, sin diferencia entre los dos primeros, pero con la ventaja de que con ozonopuntura más infiltración intrarticular se obtuvo la mejoría con menos sesiones que cuando solo se aplicó ozono por la vía intrarticular. No se reportaron eventos adversos en los grupos tratados con ozono.

Conclusiones: se recomienda la terapia con ozonopuntura combinada con infiltración intrarticular en el tratamiento de la artrosis de rodilla con más de 5 años de evolución como método seguro y efectivo.

Huanqui, C., y cols. (2006), Eficacia y seguridad del ozono intraarticular en artrosis de rodilla refractaria al tratamiento, Revista Peruana de Reumatología, vol. 12, núm. 1, pp. 21-26

El ozono, es una variedad triatómica del oxígeno (03), que se aplica al organismo humano con fines terapéuticos, sobre todo en enfermedades crónicas con poco beneficio de la medicina alopática, tal es el caso de enfermedades reumáticas como la osteoartritis (OA).

Se evalúan 100 pacientes con diagnóstico de OA primaria de rodillas grado 111, con pobre respuesta clínica a los anti inflamatorios no esteroideos (AINES), a quienes se aplica ozono intraarticular de rodillas, en dosis de 5 ce a 15 ug!ml las primeras 5 sesiones y de 5 ce a 20 ug/ml las restantes 3 sesiones, con una frecuencia de 2 infiltraciones semanales.

Utilizando el cuestionario WOMAC-escala de Likert en la evaluación del dolor, rigidez articular, dificultad funcional, expresados según puntaje acumulado, observamos una disminución progresiva en forma significativa del puntaje a los 7, 14 y 28 días de tratamiento, al término del cual el porcentaje de mejoría en los 3 parámetros clínicos evaluados fue del 52%. Los efectos adversos no fueron de consideración, salvo el dolor agudo y transitorio de rodillas durante el momento de la administración del ozono. La administración de AINES concomitantes se redujo en forma importante.

Se concluye que el ozono intraarticular es una terapia efectiva en el tratamiento de OA de rodillas grado 111 resistentes al tratamiento con AINES.

Artritis

Aliyev, D., et al. (2023), Efficacy of an intra-articular ozone injection for chronic knee pain due to osteoarthritis, Alternative Therapies in Health and Medicine, vol. 29, is. 1, pp. 24-28

Context: Osteoarthritis (OA) is the most common form of arthritis, affecting an estimated 302-million people worldwide, and it’s a leading cause of disability among older adults. Current treatments for OA are largely unsatisfactory. Ozone is an inexpensive, accessible, and easily applicable treatment for OA. Objective: The study aimed to retrospectively evaluate the effects of a short-term, three-month OA treatment using an intra-articular ozone injection, on pain and physical function in patients with stage 2-3 knee OA. Design: The research team designed the study as a retrospective review of files from a hospital’s archive as well as the results of a follow-up questionnaire about pain that patients completed at a related clinic. SETTING: The study took place at the Algology Clinic at Ankara University in Ankara, Turkey. PARTICIPANTS: Participants were 94 patients, aged between 28 and 75 years, with stage 2-3 OA who had applied to the clinic between January 1, 2018 and January 1, 2020 and had received an intra-articular ozone injection. Intervention: Participants received intra-articular ozone treatments at a dose of 10 ml at 15 mcg/ml for 4 weeks, once a week. Outcome measures: Participants completed a visual analogue score (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), measuring pain at baseline and at one month and at 3 months postintervention. The study also determined if the treatment had an effect on analgesic drug use and measured patient satisfaction. Results: The decreases in participants’ pain scores on both scales were statistically significant at one month and at 3 months postintervention (P = .000). The need for analgesic medication had decreased for 56 participants (61.5%) at one month postintervention and for 50 (54.9%) at 3 months postintervention. Of the 94 participants, 66 (70.2%) were satisfied and 28 (29.8) weren’t. Conclusions: The intra-articular injection of ozone, applied once a week for 4 weeks, resulted in a reduction in pain in stage 2-3 knee OA, without any side effects. However, further studies are needed to resolve the uncertainties in dosage, number of sessions, and intervals for intra-articular ozone injections. The current study’s results need support from further prospective studies that can evaluate the efficacy of ozone treatment for a longer period of time.

Sconza, C., et al. (2023), Ozone therapy versus hyaluronic acid injections for pain relief in patients with knee osteoarthritis: preliminary findings on molecular and clinical outcomes from a randomized controlled trial, International Journal of Molecular Sciences, vol. 24, no. 10, p. 8788, doi: 10.3390/ijms24108788

Ozone therapy (OT) is used for the treatment of multiple musculoskeletal disorders. In recent years, there has been a growing interest in its use for the treatment of osteoarthritis (OA). The aim of this double-blind randomized controlled trial was to evaluate the efficacy of OT compared with hyaluronic acid (HA) injections for pain relief in patients with knee OA. Patients with knee OA for at least three months were included and randomly assigned to receive three intra-articular injections of ozone or HA (once a week). Patients were assessed at baseline and at 1, 3, and 6 months after the injections for pain, stiffness, and function using the WOMAC LK 3.1, the NRS, and the KOOS questionnaire. Out of 55 patients assessed for eligibility, 52 participants were admitted to the study and randomly assigned into the 2 groups of treatment. During the study, eight patients dropped out. Thus, a total of 44 patients, reached the endpoint of the study at 6 months. Both Group A and B consisted of 22 patients. At 1-month follow-up after injections, both treatment groups improved statistically significantly from baseline in all outcomes measured. At 3 months, improvements remained similarly consistent for Group A and Group B. At 6-month follow-up, the outcomes were comparable between the 2 groups, showing only a worsening trend in pain. No significant differences were found between the two groups in pain scores. Both therapies have proven to be safe, with the few recorded adverse events being mild and self-limiting. OT has demonstrated similar results to HA injections, proving to be a safe approach with significant effects on pain controlin patients affected by knee OA. Due to its anti-inflammatory and analgesic effects, ozone might be considered as a potential treatment for OA.

Zhang, Y., et al. (2023), Effects of joint irrigation combined with ozone injection on bone metabolism, inflammatory factors, and joint function in knee osteoarthritis, American Journal of Translational Research, vol. 15, no. 1, pp. 213-222

Objective: To explore the effects of joint irrigation combined with ozone injection on bone metabolism, inflammatory factors, and joint function in patients with knee osteoarthritis (KOA). Method: In this retrospective study, a total of 132 KOA patients admitted to No. 215 Hospital of Shaanxi Nuclear Industry from October 2019 to July 2021 were enrolled. Among them, 62 patients received arthroscopic irrigation alone were assigned into a control group, and the remaining 70 patients who received arthroscopic irrigation combined with ozone injection were assigned into an observation group. Therapeutic efficacy and adverse reactions during the treatment were compared in the two groups. Bone metabolism, inflammatory factor levels and joint function of patients before and after treatment were observed; patients were further divided into a good prognosis group and a poor prognosis group regarding their prognosis. Multivariate analysis was performed to explore the independent risk factors affecting prognosis. Results: After treatment, compared to the control group, the total effective rate of the observation group was higher (P<0.05), and there was no notable difference in the incidence of adverse reactions between the two groups (P>0.05). The bone metabolism indexes, osteocalcin (OC) and osteoprotegerin (OPG), in the observation group were also significantly higher (P<0.05), while the level of nuclear transcription factor κB receptor activator ligand (RANKL) in the observation group was markedly lower. The inflammation level in the observation group was lower (P<0.05). Lysholm score in the observation group was strikingly higher (P<0.05), while its Western Ontario McMaster (WOMAC) score and visual analogue scale (VAS) were lower (P<0.05). The observation group had a lower rate of poor prognosis (P<0.05). Age (OR: 1.786, 95% CI: 1.347-2.370), disease duration (OR: 1.132, 95% CI: 1.002-1.279), VAS after treatment (OR: 2.316, 95% CI: 1.089-4.925), and post-treatment IL-6 (OR: 1.186, 95% CI: 1.017-1.382) were all independent risk factors for poor prognosis. Conclusion: Joint irrigation combined with ozone injection shows good efficacy in the treatment of KOA, and could effectively relieve the clinical symptoms of patients, improve their bone metabolism indexes, and help the recovery of knee joint function.

Lesiones articulares

Borroto, V., y cols. (2013), Ozonopuntura en el tratamiento de la artrosis de rodilla, Revista Cubana de Medicina Física y Rehabilitación, vol. 5, núm. 1, pp. 43-54

Objetivo: determinar el efecto de la combinación de la infiltración intrarticular de ozono combinado con ozonopuntura para el tratamiento de la artrosis de rodilla.

Métodos: se realizó un estudio aleatorizado, prospectivo, longitudinal en 60 pacientes mayores de 55 años de edad, con diagnostico clínico y radiológico de artrosis de la rodilla, que acudieron al Servicio de Calidad de Vida del Centro Nacional de Medicina Natural y Tradicional en el periodo comprendido desde enero de 2009 a enero de 2010. Se dividió la muestra en tres grupos: 1) Control, se aplicó antinflamatorios no esteroideos. 2) Se aplicaron 15 infiltraciones intrarticulares con ozono dos veces por semana. 3) Se aplicaron 15 sesiones de ozonopuntura en las rodillas, además del tratamiento utilizado con el Grupo 2. Se evaluaron antes, después, y a los seis meses de concluido el tratamiento, se evaluaron las variables siguientes: el grado de mejoría clínica, la cantidad mínima de aplicaciones con que se logra la mejoría, la incidencia de eventos adversos.

Resultados: el grupo tratado solo con infiltraciones intrarticulares de ozono y el tratado con infiltraciones con ozono intrarticulares más en puntos de acupuntura, fueron estadísticamente superiores a los del grupo tratado con antinflamatorios no esteroideo, sin diferencia entre los dos primeros, pero con la ventaja de que con ozonopuntura más infiltración intrarticular se obtuvo la mejoría con menos sesiones que cuando solo se aplicó ozono por la vía intrarticular. No se reportaron eventos adversos en los grupos tratados con ozono.

Conclusiones: se recomienda la terapia con ozonopuntura combinada con infiltración intrarticular en el tratamiento de la artrosis de rodilla con más de 5 años de evolución como método seguro y efectivo.

Méndez, I., y cols. (2010), Ozonoterapia sistemática e intra-articular en la artritis de la articulación temporomandibular por artritis reumatoide, Revista CENIC Ciencias Biológicas, vol. 41, núm. 3, pp. 169-172

Se estudió el efecto de la ozonoterapia intra-articular combinada con la vía sistémica (vía rectal) y se comparó con la sola aplicación por vía intra-articular en pacientes con artritis de la articulación temporomandibular (ATM) por artritis reumatoide (AR) mediante la evaluación clínica del dolor a la masticación, chasquido y trismo. Fueron estudiados veinte pacientes, divididos en dos grupos de diez cada uno: el primero recibió ozonoterapia intra-articular (concentración de ozono 10 mg/L y volumen de 3 mL, a razón de dos aplicaciones por semana, durante cinco semanas); y el segundo, terapia combinada (igual al primer grupo más ozono administrado por insuflación rectal, a una concentración de 30 hasta 40 mg/L y un volumen de 100 hasta 200 mL, veinte aplicaciones). Se evaluó el grosor del cartílago articular (por ultrasonido), al inicio y al final del tratamiento al igual que los síntomas clínicos: dolor a la masticación, chasquido y trismo. Como resultado, se obtuvo una disminución significativa de todos los síntomas estudiados, así como del grosor del cartílago articular diagnosticado en el estudio ultrasonográfico, teniendo una respuesta más rápida en el grupo de la terapia combinada. Se concluyó que ambas formas de tratamiento demuestran efectos beneficiosos en la artritis de la articulación temporomandibular de pacientes con artritis reumatoide, aunque la terapia combinada resulta la más eficiente, resultado que no ha sido reportado con anterioridad.

Dolor en articulaciones

Valdés, J., and M. Galiano (2021), Ozonetherapy as an Alternative to Pain Treatment in Temporomandibular Disorders, Acta Scientific Neurology, vol. 4, is. 3, pp. 46-52

Introduction: The temporomandibular disorders are very frequent; few studies exist that reflect the effectiveness of the ozone application intraarticular in the temporomandibular joint.

Purpose: To evaluate the remission time of pain in the studied patients after the ozone therapy application.

Material and Methods: An intervention study was realized in patients of the International Centre of Investigations of Ozone in La Havana, Cuba. Ozone (O3) was applied with the OZOMED Plus equipment. Ozone was applied intraarticular for ten sections 3 mg/L for a volume of 3 ml equivalent 0.03 mg in one bilateral section. Also combined with a rectal application at a dose of 30 to 40 mg / L for a volume of 200 ml per 20 continuous sections (daily).

Results: The patient with pain (100%) remitted before the ozone’s fourth application. The patient of the oral opening limitation (100%) relaxed in intensity continued of mandibular deflection and deviation.

Conclusions: The intra-articular and rectal is a safe method for pain relief in the Temporomandibular Disorder and remitted beforethe fourth treatment session.

Dolor de espalda

Elmounedi, N., et al. (2024), Ozone therapy (O₂-O₃) alleviates the progression of early intervertebral disc degeneration via the inhibition of oxidative stress and the interception of the PI3K/Akt/NF-κB signaling pathway, International Immunopharmacology, vol. 129, 111596, doi: 10.1016/j.intimp.2024.111596

Intervertebral disc degeneration (IDD) stands for the most frequent cause of low back pain. Finding a cure for this disease is an important challenge as current conservative treatments and surgical interventions fail to bring a solution to this disease. Ozone therapy (O2-O3) has yielded outstanding outcomes in intervertebral disc pathology. The ozone’s efficacy in the treatment of IDD remains unconfirmed. This study aimed to assess the effectiveness of intradiscal ozone injection on IDD induced in a rat. Effects of ozone therapy on the viability of nucleus pulposus cells were evaluated by CCK-8 assays. Macrophage immunoreactivity was detected by immunohistochemical, the expression of collagen type II was evaluated by western blot, and measurement of oxidative stress parameters was realized. Molecular docking studies were carried out in order to predict the interaction formed between O3 and the target enzymes, on the one hand, O3 with PI3K and, on the other hand, O3 with COX-2. IRM, X-ray, hematoxylin-eosin, and bleu alcian staining were realized to assess the therapeutic impacts of ozone in the puncture-induced rat model of IDD. In vivo, O3 ameliorated the IDD in the early stage of this disease. It was also displayed in molecular docking that O3 might bind to PI3K to suppress the PI3K/Akt/NF-κB signaling pathway. This study’s results show that the O3 should be administered at the low grade of IDD and at an early stage because it cannot restore the advanced inflammatory alteration of the IVD. Our results corroborated also that O3 inhibits the progression of IDD via the PI3K/Akt/NF-κB signaling pathway, which supports O3 as an effective therapeutic option for treating IDD.

Latini, E., et al. (2024), Intramuscular paravertebral oxygen-ozone therapy for chronic neck pain and low back pain: evaluation of 6-month clinical outcomes, Medical Gas Research, vol. 14, no. 1, pp. 6-11, doi: 10.4103/2045-9912.374388

Spinal pain is recognized as the most common cause of disability, work absenteeism and need of healthcare services worldwide. Although many strategies have been developed for conservative treatment of spinal pain, its increasing prevalence diagnosis highlights the need for new treatments. Oxygen-ozone (O2–O3) therapy is considered to be an alternative therapy due to its analgesic and anti-inflammatory effects. This retrospective study evaluated the effects of O2–O3 intramuscular paravertebral injections in 76 patients with chronic neck pain or low back pain, in terms of pain and disability reduction, quality of life improvement, and analgesic drug intake. Patients were evaluated before, at the end of the treatment, and at 1, 3 and 6 months after the last treatment, using Numeric Rating Scale, Neck Disability Index or Oswestry Disability Index, and Short Form-12 Health Survey. There were significant beneficial effects of O2–O3 therapy in reducing pain and disability reduction and improving quality of life during the 6-month follow-up period. O2–O3 therapy was associated with a reduction in analgesic drug intake at each assessment. Our results allow us not only to support treatment with O2–O3 intramuscular paravertebral injections as a safe and beneficial treatment for chronic low back pain, but also to consider it as a valuable conservative therapy for patients with chronic neck pain.

Rania, V., et al. (2023), Oxygen–ozone therapy in cervicobrachial pain: a real-life experience, Journal of Clinical Medicine, vol. 12, no. 1, p. 248, doi: 10.3390/jcm12010248

This prospective, open-label clinical study was carried out to evaluate both the efficacy and safety of intramuscular paravertebral injections of an oxygen–ozone (O2–O3) mixture in patients with cervicobrachial pain. We enrolled 540 subjects affected by cervicobrachial pain referred to the Ozone Therapy Ambulatory at the Mater Domini Hospital of Catanzaro (Italy) and to the Center of Pain in Taurianova (Reggio Calabria, Italy). All the subjects (n = 540) completed the treatment and the followup visits. The subjects received a mean of 11 cervical intramuscular treatments with an O2–O3 mixture (5 mL) with an O3 concentration of 10 g/mL bis a week. The improvement of pain was measured by a change in the mean of the Visual Analog Scale (VAS) score from baseline to the end of treatment and during follow-ups. Patient satisfaction was assessed at the end of treatment using the SF-36 Questionnaire. The development of adverse drug reactions was recorded. The mean (standard deviation) VAS pain score at baseline, at the end of treatment, and during follow-ups showed a significant reduction in pain over time (p < 0.001). All the patients who were enrolled (n: 540) were pain-free after one year. According to the pain distribution, all subjects showed a significant reduction in pain over time in each group (p < 0.05). No significant differences were observed with respect to sex or age. No adverse events were observed during the study. In conclusion, we documented that the intramuscular injection of an O2–O3 mixture is an effective and safe treatment option for patients with cervicobrachial pain.

Davidovic, K., et al. (2023), Percutaneous computed tomography-guided oxygen-ozone (O₂O₃) injection therapy in patients with lower back pain — an interventional two-year follow-up study of 321 patients, Diagnostics, vol. 13, no. 21, 3370, 14 p., doi: 10.3390/diagnostics13213370

Objectives: To assess the effect of oxygen-ozone therapy guided by percutaneous Computed Tomography (CT) compared to corticosteroids in individuals experiencing lower back pain (LBP) not attributed to underlying bone-related issues. Methods: A total of 321 patients (192 males and 129 females, mean age: 51.5 15.1 years) with LBP were assigned to three treatment groups: group A) oxygen-ozone only, group B) corticosteroids only, group C) oxygen-ozone and corticosteroids. Treatment was administered via CT-guided injections to the intervertebral disc (i.e., intradiscal location). Clinical improvement of pain and functionality was assessed via self-reported pain scales and magnetic resonance (MR) and CT imaging. Results: At all follow-up times, the mean score of the numeric rating scale and the total global pain scale (GPS) of study groups receiving oxygen-ozone (groups A and C) were statistically significantly lower than the study group receiving corticosteroids only (group B), with p < 0.001. There was a statistically significant difference between groups A and C at 30 days for the numeric rating scale. Conclusions: The percutaneous application of oxygen-ozone in patients with LBP due to degeneration of the lumbosacral spine showed long-lasting significant pain reduction of up to two years post-treatment when compared to corticosteroids alone. Combination therapy of oxygen-ozone and corticosteroids can be useful as corticosteroids showed statistically significant improvement in LBP earlier than the oxygen-ozone-only treatment.

Hernia discal

Balasaheb, S., et al. (2023), Ozone disc nucleolysis in the management of herniated lumbar intervertebral disc: a retrospective analysis, Journal of Craniovertebral Junction and Spine, vol. 14, no 1, pp. 16-23, doi: 10.4103/jcvjs.jcvjs_141_22

Background: Various minimally invasive surgeries were proposed for the management of herniated lumbar intervertebral disc. However, to choose optimal treatment modality to maximize patient benefit is a clinical challenge for the treatment givers.

Objective: The objective was to study the role of ozone disc nucleolysis in the management of herniated lumbar intervertebral disc by retrospective analysis.

Methodology: We conducted a retrospective analysis of patients of lumbar disc herniation treated by ozone disc nucleolysis during May 2007–May 2021. There were total of 2089 patients with 58% of males and 42% of females. The age ranged from 18 to 88 years. Outcome was measured on the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI) along with modified MacNab method.

Results: The mean baseline VAS score was 7.73, which became 3.07 at 1 month, 1.44 at 3 months, 1.42 at 6 months, and 1.36 at 1 year. Similarly, the mean ODI index was 35.92 at baseline, which improved to 9.17 at 1 month, 6.14 at 3 months, 6.10 at 6 months, and 6.09 at 1 year. VAS score and ODI analysis was found to be statistically significant with P < 0.05. Modified MacNab criterion showed successful treatment outcome in 85.6% with excellent recovery in 1161 (55.58%), good recovery in 423 (20.25%), and fair recovery in 204 (9.77%). Mediocre or no recovery was seen in the remaining 301 patients amounting to a 14.40% failure rate.

Conclusion: This retrospective analysis confirms that ozone disc nucleolysis is an optimally effective and least invasive treatment option for herniated lumbar intervertebral disc with a significant reduction in disability.

Alexandre, A., et al. (2023), Intradiscal injection of oxygen-ozone gas mixture for the treatment of contained cervical disc herniations, European Journal of Musculoskeletal Diseases, vol. 12, no. 2, pp. 51-56, doi: 10.1007/3-211-27458-8_17

For disc herniations, open surgical approaches are reduced since new percutaneous methods allowing shrinkage of the disc and improvement of the radicular function are gaining interest. Studies on the spontaneous disappearance of disc fragments have demonstrated autoimmune responses with a chronic inflammatory reaction. Also, radicular pain is due mainly to biochemical mechanisms. Researchers in different fields surprisingly noticed that a brief, calculated oxidative stress by ozone administration might correct a persistent imbalance due to excessive, chronic oxidative injury. Oxygen-ozone gas injection in painful patients has a dramatic effect on clinical symptoms.

On these bases, the intradiscal injection of oxygen-ozone gas has been conceived. We report the treatment on a series of patients affected by cervical disc pathology, treated by intradiscal injection of an oxygen-ozone gas mixture. The effects both on pain and on radicular dysfunction are impressive. The morphological effrect of the treatment was also evaluated by pathological examination.

Espinosa, A. y A. Schwartz (2023), Hernia de disco lumbar extruida tratada con ozonoterapia, Ozone Therapy Global Journal, vol. 13, no. 1. pp. 81-99

La ozonoterapia se está utilizando desde hace años con éxito en el tratamiento de la hernia de disco lumbar y está respaldada por numerosos estudios clínicos. Presentamos el caso de una mujer de 55 años con hernia de disco lumbar extruida que debutó con ciática aguda y paresia en L5. La paciente rechazó el tratamiento quirúrgico a pesar de ser buena candidata al mismo. Fue sometida a ozonoterapia con infiltraciones ecoguiadas por vía caudal y foraminal (dosis de 20 mL a 20μg/mL) y paravertebral (10 mL a 20 μg/mL). En 10 días el dolor neural desapareció y a los 3 meses hacía vida normal. Una resonancia hecha a los 6 meses demostró la completa reabsorción de la hernia.

Salud de la columna

Sumida, J., et al. (2023), Randomized single-blinded prospective comparison between ozone therapy and electroacupuncture for canine thoracolumbar disk disease, Research in Veterinary Science, vol. 161, no. 2, pp. 173-179, doi: 10.1016/j.rvsc.2023.06.019Get rights and content

Ozone therapy has been used to control pain in animals. Moreover, electroacupuncture (EA) has been effective in neurological recovery and pain control in dogs with thoracolumbar discopathy. EA was compared with Ozone applied at acupuncture points in dogs with signs of thoracolumbar disk disease. Chondrodystrophic mongrel dogs, with lesion scores between 1 and 4, were randomly divided into groups: EA (n = 13) – electroacupuncture at BL20, BL23, ST36, KID3 and BL60 and dry needle in lumbar Bai Hui, and OZO (n = 15) – paravertebral application of 3 mL ozone (20 μg / mL) at BL20, BL23, lumbar Bai Hui, ST36, and KID3/BL60, both groups with weekly applications. No significant differences were observed between groups in weekly blind pain assessments using a dynamic interactive visual analog scale, and neurological assessments using a numerical-functional scale. Both groups showed a progressive improvement in pain control and neurological condition, which was observed when comparing the group’s EA and OZO in dogs with all lesion scores. The time of return to locomotion (days) of dogs scored 3 and 4, between groups EA (10.6 ± 5.4) and OZO (14.5 ± 15.7), had no significant differences. Ozone therapy was effective to control pain and motor rehabilitation and sensory functions of dogs with thoracolumbar discopathy signs, just as electroacupuncture. Ozone application was a quick and easy-to-handle treatment. Paravertebral and subcutaneous routes did not require anesthesia or other advanced imaging technology, besides being safe and effective

Masala, S., et al. (2023), CT-guided ozone mixture injection in treatment of symptomatic lumbar facet synovial cysts, Acta Bio Medica: Atenei Parmensis, vol. 94, no 1, p. e2023025, doi: 10.23750/abm.v94i1.12991

Background and aim: To evaluate the clinical and radiological outcomes, in terms of safety and efficacy, of a new treatment method for symptomatic lumbar facet synovial cysts (LFSC), based on ozone injection inside the cyst. Methods: We retrospectively reviewed clinical records and imaging studies of 77 patients who underwent CT-guided ozone treatment of symptomatic facet joint synovial cysts in our department over a 5-year span. Clinical outcome was assessed with Numerical Rating Scale (NRS) and Oswestry Disability Index (ODI) evaluations, obtained prior to the intervention and at 1-, 3-, 6- and 12-months follow-up. Follow-up MRI imaging at 6 and 12 months were obtained and confronted with the pre-procedural MRI to analyse cyst modification after the intervention. Results: Ozone administration was technically successful in 100% of procedures; no immediate complications occurred. At 1 month evaluation, 92% of the patients referred partial or complete symptomatic response; 86% of patients at 3 months and 84% at 6 months confirmed symptoms improvement; final assessment, at 12 months after intervention, outlined overall significant clinical improvement in 81% of patients. During the 12 months of follow-up only 3 patients had a relapse of the cyst (at 6 months) that were retreated with a 100% success. Conclusions: CT-guided ozone therapy for symptomatic LFSC is a safe and innovative treatment option, with good clinical results at 12 months follow-up in a significative percentage of patients, thus reducing the need for invasive surgical interventions.

Dermatología

Machado, A., et al. (2022), Effectiveness and safety of ozone therapy for dermatological disorders: aliterature review of clinical trials, Indian Journal of Dermatology, vol. 67, no 4, p. 479, doi: 10.4103/ijd.ijd_152_22

Ozone is a strong oxidizing agent, capable of promoting therapeutic effects such as antimicro‐ bial, anti inflammatory, antioxidant and healing activities, with low probability of toxicity whenused in a specific dosage range. The aim of this study was to conduct a literature review to as‐ sess clinical trials available over the past 10 years regarding the effectiveness and safety ofozone therapy to treat dermatological disorders. The search for bibliographic material wascarried out through PubMed, Cochrane Library and Google Scholar electronic databases. Theinclusion criteria covered only controlled clinical trials published from 2011 to 2021 and writ‐ ten in English. The 18 selected clinical trials included 1279 patients (ranging from 12 to 400patients per study), of which 1185 patients were adults and 94 were children. Ozone therapywas evaluated regarding the treatment of diabetic foot ulcers, digital ulcers, chronic venous legulcers, atopic dermatitis, skin burns, onychomycosis, tinea pedis, cutaneous leishmaniasis, bal‐ anitis xerotica obliterans and multiple common warts. Only three studies, addressing the treat‐ ment of cutaneous leishmaniasis, skin ulcers and skin burns, evidenced lack of effectiveness ofozone treatment. Mild adverse effects occurred in three clinical trials, whereas severe side ef‐ fects occurred in only one clinical trial, regarding skin ulcers. Therefore, ozone therapy may besuggested as an alternative or complementary treatment in some types of dermatological con‐ ditions specially affecting refractory patients. Though, a greater number of high-quality clinicaltrials is needed to clearly establish the safety of ozone therapy in dermatological disorders.

Kim, S., et al. (2024), Ozonated sunflower oil (OSO) alleviates inflammatory responses in oxazolone-induced atopic dermatitis (AD)-like mice and LPS- treated RAW 264.7 cells, Journal of Microbiology and Biotechnology, vol. 34, no. 4, pp. 1-10, doi: 10.4014/jmb.2310.10037

Ozone, a highly reactive oxidant molecule, is widely used as acomplementary therapy for various skin diseases, including woundhealing, pressure ulcers, diabetic foot, and infections. However, there islimited research on the effectiveness of ozone for atopic dermatitis (AD).Ozonated sunflower oil (OSO) is an active ingredient obtained frompartially ozonated sunflower oil (SO). OSO markedly reduced the LPS-induced increase in IL-1β and nitric oxide (NO) levels in RAW 264.7 mouse macrophage cells. Oxazolone (OXZ) was applied to hairless miceto induce AD-like skin symptoms and immune response. OSOsignificantly alleviated the OXZ-induced increases in the number ofinfiltrating mast cells, epidermal thickness, AD symptoms, thymicstromal lymphopoietin (TSLP), and filaggrin, as well as the serum levelsof NO, IgE, IL-1β, and TNF-α. Furthermore, OSO inhibited the IL-4/STAT3/MAPK pathway and the expression of NF-κB. Our results suggestthat OSO treatment could relieve AD-mediated skin damage through itsanti-inflammatory and antioxidant activities. Therefore, it can be used asa therapeutic agent against AD-related skin diseases.

Acné

Khaoshi, X., and C. Zhang (2020), Formulation and clinical evaluation of ozonated olive oil for the treatment of acne vulgaris lesions, Stem Cell, vol. 11, no. 2, pp. 54-60, doi: 10.7537/marsscj110220.08

The ozonides produced by ozonation procedure have significant killing effects on bacteria, fungi and yeasts. They have effects on activation of local microcirculation, tissue growth, and on other processes involved in the treatment of skin disorders. The purpose of present study is to formulate and evaluate the healing effects of ozonated extra virgin olive oil on acne vulgaris as a single-blind, non-randomized clinical trial. Each patient received a placebo on his/her lesions for one month and after 10 days of washouts, they were treated with ozonated olive oil applied on their whole lesions for one month. The results were expressed as the percentages of reduced inflammatory versus non-inflammatory lesions. After one month of ozonated olive oil treatment, a seventy-five percent healing was observed in 50% of patients while under the same condition the remaining twenty five percent of the patients had 50% healing. After one month of applying ozonated olive oil, both inflammatory and noninflammatory acne lesions were decreased by 65%. In conclusion, topical application of ozonated olive oil has shown significant healing effects on patients suffering from acne vulgaris. Biocompatibility behavior of ozonated olive oil makes it an excellent candidate to be prescribed as a highly potential anti-acne medicine.

Davis, V. (2018), Clinical improvement of severe chronic acne conglobata. Case Report, Revista Española de Ozonoterapia, vol. 8, núm. 1, pp. 109-115

Chronic severe acne conglobata is a severe form of acne presenting with multiple deep abscesses. It is frequently a debilitating and painful condition. Treatment options include long-term systemic antibiotics, intralesional steroid injections, systemic retinoids, systemic steroids, adalimubab, electron beam radiation, and topical treatment.1 These treatments frequently lack efficacy and may have risks of significant side effects. Ozone therapy has been used successfully in treating acne and cysts. A 34 year-old white male presented with chronic, large, numerous, painful draining cysts of the trunk, groin and neck of ten years duration. The patient reported excessive alcohol ingestion and suicidal thoughts due to the pain. Past treatments with antibiotics and steroids were unsuccessful. During a period of one year the patient was treated with ozone: topical ozonated oil, full-body bag topical ozone, intralesional ozone, and ozone minor autohemotherapy. The patient reports a reduction in the number of daily lesions, reduction in pain, reduction in lesion drainage, decreased lesion resolution, an optimistic life outlook, and reduction of alcohol intake. The success of ozone therapy in this case indicates ozone therapy is a safe and effective option for patients with severe debilitating chronic acne conglobata.

Psoriasis

Gao, L., et al. (2020), Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis, Journal of Cellular and Molecular Medicine, vol. 24, no. 8, pp. 4819-4829, doi: 10.1111/jcmm.15160

Psoriasis is a chronic immune-mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL-17 and IL-22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down-regulated KRT6 mRNA and protein expression while up-regulated KRT10 mRNA and protein expression within IL-22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expresión of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63-mediated transcription of KRT10, therefore improving psoriasis.

Rosácea

International Scientific Committee for Ozone Therapy (2020), Declaración de Madrid sobre la ozonoterapia, 3ª edición, ISCO3, ed., Madrid, p. 38

Aceite ozonizado. Indicaciones. 400 IP: Para administración oral, en post-cirugía171 y enfermedades del tracto intestinal como Helicobacter pylori. Uso tópico en revitalización facial, la rosácea, el acné y la estimulación de la granulación.

Estética

Dos Santos, F. et al. (2021), Fundamentals of the use of ozone therapy in the treatment of aesthetic disorders: a review, Journal of Biosciences and Medicines, vol. 9, no. 12, pp. 40-70, doi: 10.4236/jbm.2021.912005

Considering the great interest of many professionals in the foundation that guides the effective use of ozone therapy in the treatment of aesthetic disorders, this study aims to define the physiological and practical aspects of using the oxygen-ozone mixture to solve aesthetic problems. Exploratory research was carried out, presented in a narrative review, to highlight the action of ozone therapy in the treatment of aesthetic affections. The review explored scientific articles, books, theses, and dissertations published and available in the following databases: MEDLINE (Medical Literature Analysis and Retrieval System Online), PubMed (National Library of Medicine), SCIELO (Scientific Electronic Library Online), and LILACS (Latin Literature American and the Caribbean in Health Sciences). In addition, elements that characterize the authors’ clinical experience on ozone therapy in various aesthetic treatment protocols were added. We found several reports in the literature that justify the use of ozone and its different therapeutic modalities in various aesthetic affections, mainly in the treatment of localized fat, cellulite, rejuvenation, skin tissue repair, acne, dyschromia, and others. Through its various therapeutic modalities, we conclude that ozone therapy has added a lot to aesthetic procedures, mainly for its effective supporting action or as the main agent of critical physiological changes to enhance clinical results when treating aesthetic conditions.

Rejuvenecimiento facial

De Castro, R., et al. (2023), Biostimulating effect of ozone therapy on facial rejuvenation, a multilayered approach with combined therapies: a case report and literature review, Ozone Therapy Global Journal, vol. 13, no. 1, pp. 101-116

Backgorund: The search for aesthetic improvement of the skin and searching for effective methodologies that can generate good safe results in a short period of time is a constant. Ozone therapy is also indicated for improving skin aesthetics, adjusting tissue oxidative levels, increasing collagen production and even skin volumizing.

Aims: Biostimulators promote neocollagenesis and skin densification restoring tissue vitality and generating a great impact on the patient’s emotional health. This paper aims to carry out a case report that demonstrated positive results of the biostimulating effect of ozone therapy, used alone and in association with other techniques, supporting the technique in the literature review.

Patients / Methods: A case report that demonstrated positive results of the biostimulating effect of ozone therapy, used alone and in association with other techniques as botulinum toxin and jett plasma.

Results: The application of ozone therapy showed positive results for biostimulating activities in the reported cases demonstrating to be a viable clinical technique.

Conclusions: Biostimulating effect of ozone therapy is a promising aesthetic therapeutic modality with fast and safe results, the versatility in association with other techniques reinforces the clinical importance of ozone therapy as an aesthetic therapeutic option.

Celulitis

Cuccio, G. and M. Franzini (2016), Oxyen-ozone therapy in the treatment of tissue adipose diseases, Ozone Therapy, vol. 1, no. 2, pp. 25-33, doi: 10.4081/ozone.2016.6270

The panniculosis or panniculopathy edematous fibro sclerotic (PEFS), commonly called cellulite is a subcutaneous adipose disease that afflicts the vast majority of women at all ages. PEFS is framed as a subcutaneous adipose suffering from venous and lymphatic stasis whose etiology is multifactorial. Many others are the implications and clinical relapses of diseases of inflammatory or autoimmune basis that determine disease states with involvement of the patient’s general conditions. The oxygen-ozone therapy, thanks to its abilities of improving the rheological properties of the microcirculation, immuno-modulating and anti-inflammatory abnormalities, arises as adjuvant and is a valid method, which is also alternative compared to conventional protocols.

Lipólisis

Varäo, J. (2020), Tratamiento de lipólisis de grasa submentoniana con ozonoterapia y sus efectos en el síndrome de apnea obstructiva crónica y estética, Ozone Therapy Global Journal, vol. 10, no. 1, pp. 207-239

La acumulación de grasa en la región submentual representa una desventaja estética importante, originando la papada y además implica un problema de salud grave, pues está asociada a la apnea del sueño, el estrés oxidativo e incluso la muerte por hipoxia cerebral y paro respiratorio en una gran parte de la población en todo el mundo. Este estudio tuvo como objetivo evaluar la terapia de ozono como herramienta segura para tratar el exceso de la grasa localizada, ya que los otros procedimientos comúnmente utilizados tienen efectos secundarios cuestionables, como alteraciones de la función hepática y cambios en la homeostasis. El estudio es una revisión de la literatura con ozonoterapia, sus formas de administración, concentraciones, periodicidad, contraindicaciones, en las situaciones y comorbilidades prescritas para valorar y evaluar una propuesta terapéutica efectiva y segura en la reducción volumétrica de la grasa submentual. Se revisaron las bases de datos MedLine de PubMed y Zotero ISCO3 de los artículos publicados entre 1990 a 2020, usando las palabras clave: ozono terapia, apnea obstructiva del sueño, grasa submentual, lipólisis. El estudio sugiere que la ozonoterapia es efectiva y tiene baja incidencia de efectos colaterales, y requiere más estudios clínicos con muestras amplias para establecer protocolos en su aplicación, con seguimiento del paciente por un tiempo más prolongado para verificar la eficacia del tratamiento a largo plazo.

Regeneración de tejidos

Hidalgo-Tallón, F., et al. (2023), Medical ozone on hamstring injury in a profesional athlete assessed by thermography: a clinical case report, BJR case reports, vol. 9, no. 4, 7 p., doi: 10.1259/bjrcr.20220078

Injuries associated with the hamstring muscles in the running athlete are increasingly investigated due to the economic and functional consequences associated with them. Although hardly used in the treatment of sports injuries, medical ozone is effective and very well tolerated in the treatment of musculoskeletal pain, it was decided to add a series of medical ozone infiltrations to the treatment. The evolution of the case was recorded by medical thermography, in addition to measuring pain intensity (visual analog scale) and functional capacity (toe touch test). Pain intensity (visual analog scale) decreased from seven at baseline to two at the end of treatment (after two ozone infiltrations, one weekly). Mobility of the damaged area (toe touch test) improved from a distance of 8 cm at baseline to 0 cm at the end of treatment. Regarding medical thermography, after the first and second infiltration of ozone, the temperature rose to a significant increase in perfusion from baseline from 31.2 to 31.8 °C and from 31.2 to 32 °C, respectively. These results suggest the possible interest of medical ozone as an adjuvant treatment for the recovery of sports tendinopathies and encourage us to carry out further studies.

Fatiga

Tirelli, U., et al. (2023), Oxygen-ozone autohemotherapy in breast cancer patients suffering from fatigue and musculoskeletal pain upon aromatase inhibitors treatment: a case-series study, European Review for Medical and Pharmacological Sciences, vol. 27, no. 23, pp. 11643-11652, doi: 10.26355/eurrev_202312_34602

Objective: In patients with breast cancer and positive hormone receptors, aromatase inhibitors are effective in reducing the risk of recurrences and are active in progressing the disease in this setting. On the other hand, fatigue and painful musculoskeletal side effects can significantly reduce treatment compliance. With no further treatment options to control these symptoms, non-pharmaceutical interventions, such as oxygen-ozone therapy, may play a role in managing rheumatologic symptomatology inasmuch. We have previously reported evidence on the effectiveness of oxygen-ozone in the treatment of pain and fatigue in chronic fatigue syndrome and fibromyalgia patients and in oncological patients as well.

Patients and methods: In this study, we reported 6 cases of patients (mean age 64 yrs, all Caucasian females) with breast cancer upon treatment with anastrozole (Arimidex®), suffering from musculoskeletal pain, weakness and fatigue, and therefore treated with oxygen-ozone major autohemotherapy according to the Italian Scientific Society of Oxygen Ozone Therapy (SIOOT) protocol. Pain was measured with a 10-item Numerical Rating Scale (NRS) and fatigue with a 7-item Fatigue Scoring Scale (FSS).

Results: A reduction of at least 66% of pain (from 9.43 ±0.54 SD to 2.36 ±1.32 SD, p<0.001) and 66.26% of fatigue were obtained for all the cases. Pain and fatigue disappeared within one month from ozone therapy, and a healthy painless state lasted for many months following the oxygen-ozone therapy.

Conclusions: The oxygen-ozone therapy is a sound opportunity for breast cancer patients to reduce anti-aromatase-induced pain, fatigue, and musculoskeletal symptoms.

Cansancio crónico

Tirelli, U., et al. (2022), Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) greatly improved fatigue symptoms when treated with oxygen-ozone autohemotherapy, Journal of Clinical Medicine, vol. 11, no. 1, p. 29, 10.3390/jcm11010029

(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic syndrome characterized by fatigue as its major and most outstanding symptom. Previous evidence has supported the ability of ozone to relief ME/CFS related fatigue in affected patients (2) Methods: A number of 200 ME/CFS previously diagnosed patients, (mean age 33 13 SD years) were consecutively treated with oxygen-ozone autohemotherapy (O2-O3-AHT). Fatigue was evaluated via an FSS 7-scoring questionnaire before and following 30 days after treatment. (3) Results: Almost half (43.5%) of the treated patients evolved their FSS scale from the worst (7) to the best (1) score, assessing the highest improvement from being treated with O2-O3-AHT. Furthermore 77.5% of patients experienced significant ameliorations of fatigue, of 4–6 delta score. No patient showed side effects, yet experienced long lasting fatigue disappearance, by three months follow up (4) Conclusions: Treatment with O2-O3-AHT greatly improves ME/CFS related fatigue, aside from sex and age distribution.

Tirelli, U., et al. (2019), Ozone therapy in 65 patients with fibromyalgia: an effective therapy, European Review for Medical and Pharmacological Sciences, vol. 23, no. 4, pp. 1786-1788, doi: 10.26355/eurrev_201902_17141

Objective: Fibromyalgia is a chronic disorder with a very complex symptomatology. Although generalized severe pain is considered to be the cardinal symptom of the disease, many other associated symptoms, especially non-restorative sleep, chronic fatigue, anxiety, and depressive symptoms also play a relevant role in the degree of disability characteristic of the disease.

Ozone therapy, which is used to treat a wide range of diseases and seems to be particularly useful in the treatment of many chronic diseases, is thought to act by exerting a mild, transient, and controlled oxidative stress that promotes an up-regulation of the antioxidant system and a modulation of the immune system. According to these mechanisms of action, it was hypothesized that ozone therapy could be useful in fibromyalgia management, where the employed therapies are very often ineffective.

Patients and methods: Sixty-five patients with fibromyalgia, according to the definition of the American College of Rheumatology (Arthritis Rheum 1990; 33: 160-172), were treated at the MEDE Clinic (Sacile, Pordenone, Italy) from February 2016 to October 2018. Females were 55 and males were 10; age ranged from 30 to 72 years, and the time from fibromyalgia diagnosis ranged from 0.5 to 33 years. Treatment was made by autohemotransfusion in 55 patients and by ozone rectal insufflations in 10 patients, according to SIOOT (Scientific Society of Oxygen Ozone Therapy) protocols, twice a week for one month and then twice a month as maintenance therapy.

Results: We found a significative improvement (>50% of symptoms) in 45 patients (70%). No patient reported important side effects. In conclusion, at our knowledge, this is the largest study of patients with fibromyalgia treated with ozone therapy reported in the literature and it demonstrates that the ozone therapy is an effective treatment for fibromyalgia patients without significant side effects.

Conslusions: At the moment, ozone therapy seems a treatment that, also because without any side effect, is possible to be proposed to patients with fibromyalgia that are not obtaining adequate results from other available treatments and it can be considered as complementary/ integrative medicine.

Autoinmunes

Enfermedades autoinmunes

Cabioglu, N., et al. (2023), Ozone therapy as a novel complementary therapeutic approach in refractory idiopathic granulomatous mastitis, Frontiers in Medicine, vol. 10, 174372, doi: 10.3389/fmed.2023.1174372

Background: Autoimmunity may play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). The therapeutic potential of ozone therapy has recently been shown in rheumatological diseases, and this study aimed to assess the clinical efficacy of ozone therapy (OT) in refractory IGM.

Methods: Patients with biopsy-verified IGM and incomplete response after steroid therapy (n = 47) between 2018 and 2021 were enrolled. Of these, 23 cases in cohort A had standard treatment with further steroid therapy (ST), and 24 were treated with systemic OT via autohemotherapy (AHT) in addition to steroid therapy (cohort B).

Results: The median age was 33 years (range, 24–45). Patients in cohort B had a higher complete response rate after completion of a four-month ozone therapy than those in the ST-group (OT-group, 37.5% vs. ST-group, 0%; p = 0.002). At a median follow-up of 12 months (range, 12–35), the patients treated with OT had a lower one-year recurrence in the affected breast than cases in cohort A treated with ST (OT-group, 21% vs. ST-group, 70%; p = 0.001). No significant side effects were observed in patients in cohort B related to AHT. Furthermore, OT significantly decreased the total steroid treatment duration (median week of steroid use; 26 weeks in cohort A vs. 12 weeks in cohort B; p = 0.001).

Conclusion: Systemic OT increases the complete response rate and decreases the duration of steroid treatment in patients with refractory IGM. Therefore, ozone therapy is an effective, well-tolerated, and safe novel complementary therapeutic modality.

Esclerodermia (o esclerosis sistémica, esclerodermatitis y esclerodermatitis difusa)

International Scientific Committee for Ozone Therapy (2020), Declaración de Madrid sobre la ozonoterapia, 3ª edición, ISCO3, ed., Madrid, p. 44

4.3 Enfermedades en el Nivel C

Para estas patologías la ozonoterapia se utiliza ya sea sola o como soporte para un tratamiento específico, según los casos, se convierte en un edicamento/tratamiento con una alta tasa de éxito terapéutico de acuerdo con los informes clínicos preliminares.

En algunos estudios, la combinación de la ozonoterapia con otro tratamiento ha sido evaluada, concluyendo que la ozonoterapia actúa como un complemento.

Enfermedades autoinmunes: esclerosis sistémica…

Schwartz, A., et al. (2011), Guía para el uso médico del ozono. Fundamentos terapéuticos e indicaciones, Madrid, España, pp. 59 y 290.

Especialistas alemanes en ozonoterapia demostraron en sus estudios la efectividad… y los estudios de especialistas rusos lo hicieron en el tratamiento de la esclerosis difusa (Kotov, 2000), la esclerodermatitis… (Glavinskaia y Bitkina, 1998).

Glavinskaia TA, Bitkina OA. Influencia de la ozonoterapia en el estado de los sistemas oxidantes y antioxidantes en pacientes con lupus eritematoso, Ozono y métodos de terapia eferente en medicina, Resúmenes 1^a Conferencia Cientificopráctica de toda Rusia. N. Nóvgorod, 1998, p. 111 (en ruso)

Kotov SA. Fundamentación clínico-neurofisiológica de la ozonoterapia de las enfermedades del sistema nervioso. Resumen de la Tesis de Doctor en Ciencias Médicas. Ivanovo, 2000, p. 42 (en ruso).

Lupus

Schwartz, A., et al. (2011), Guía para el uso médico del ozono. Fundamentos terapéuticos e indicaciones, Madrid, España, pp. 59 y 290.

Especialistas alemanes en ozonoterapia demostraron en sus estudios la efectividad… y los estudios de especialistas rusos lo hicieron en el tratamiento de… el lupus eritematoso diseminado (Glavinskaia y Bitkina, 1998).

Fibromialgia

Uquillas, G. (2021), Ozonoterapia por insuflación rectal y auto hemoterapia menor en el manejo de paciente con fibromialgia, Ozone Therapy Global Journal, vol. 11, no. 1, pp. 89-96

La fibromialgia es una patología crónica, caracterizada principalmente por dolor crónico músculo-esquelético, con síntomas acompañantes que deterioran la calidad de vida.

Se realizó tratamiento complementario con ozonoterapia rectal y Auto Hemoterapia menor en paciente con diagnóstico de fibromialgia, con 9 años de evolución, la intensidad del dolor inicial según la Escala Visual Analógica fue de 9/10. Se aplicaron 30 sesiones, 3 sesiones por semana. Se evidenció disminución de la intensidad del dolor en la décimo quinta sesión que obtuvo según la Escala Visual Analógica del dolor 7/10, y a la vigésima sesión de 3/10. La calidad de vida mejoró en un 80%.

Se pudo concluir que la terapia con ozono podría ayudar en aquellas pacientes con fibromialgia en las que no se ha logrado alivio del dolor con otras terapias. No se presentaron efectos adversos durante el tratamiento. Son necesarios estudios clínicos más amplios en esta dirección.

Proctología

Hemorroides

Kim, J., et al. (2020), Pain control and early wound healing effect using sitz bath with ozonised water after haemorrhoidectomy, Journal of Wound Care, vol. 29, no. 5, pp. 289-294, doi: 10.12968/jowc.2020.29.5.289

Objective: Studies have shown that ozone in an aqueous state on a scar, because of its antibacterial effect, aids wound-healing. This study aimed to compare the pain control effect, based on the time to wound healing, of using a sitz bath with ozonised water with that of using a sitz bath with ordinary tap water in patients who have had a

haemorrhoidectomy.

Method: Patients were divided into two equal-sized groups: Group O used a sitz bath with ozonised water after haemorrhoidectomy and patients in Group T used a sitz bath with ordinary tap water. Different concentrations (1ppm, 2ppm and 4ppm) of ozonized wáter were tested to determine their bactericidal activities. Pain levels were measured using the Visual Analogue Scale (ranging from 0–10 where 0 is ‘no pain’ and 10 is ‘unbearable pain’), on days two, three and seven. Cohort analysis was retrospectively performed on the prospectively randomised collected data for this study.

Results: A total of 80 patients participated in the study. No case showed any signs of bacterial growth. On postoperative day seven, patients in Group O showed a significantly lower pain level than those in Group T (1.35±0.48 versus 2.40±0.9; p<0.001). The time needed for anus scars to be completely healed was significantly shorter for Group O than that for Group T (2.75±0.63 weeks versus 3.85±0.80 weeks; p<0.001).

Conclusion: The results of this study showed that using a sitz bath with ozonised water reduced pain and accelerated healing in patients who have had a haemorrhoidectomy.

Kovalev, S., and K. Kotenko (2021), Non-drug technologies in early rehabilitation of patients after hemorrhoidectomy, Voprosy Kurortologii, Fizioterapii, i Lechebnoi Fizicheskoi Kultury, vol. 98, no. 6., Vyp. 2, pp. 65-71, doi: 10.17116/kurort20219806265

Among all coloproctological diseases, hemorrhoids rank first among the reasons for visiting a proctologist. Its prevalence is 130-145 per 1.000 adults, and its proportion in the structure of colorectal diseases ranges from 34 to 41%. After hemorrhoidectomy, a long period of rehabilitation is necessary. There are long periods of incapacity for work (at least two weeks) and quite high complications rate, which generally leads to economic burden. Therefore, an urgent problem of current coloproctology and physiotherapy is the development of new approaches to medical rehabilitation of the patients after surgery for their fast recovery and prevention of complications.

Objective: To study effectiveness of comprehensive postoperative rehabilitation program including ozone therapy, laser therapy, recto-tibial myostimulation and biofeedback therapy in patients after hemorrhoidectomy.

Material and methods: The study included 90 patients 20-65 years of age (mean age 41.4±2.1years) with chronic stage III hemorrhoids with prominent external nodules (ICD-10 code: K64.2). All patients underwent Milligan-Morgan hemorrhoidectomy using an ultrasound scalpel by the same coloproctologist to exclude the influence of personality factors. The patients were assigned into two groups by random sampling. The main group consisted of 45 patients who received standard of care and the rehabilitation program, including intravenous ozone therapy, rectal laser therapy, recto-tibial myostimulation, and biofeedback therapy starting from the second day after the surgery. The control group consisted of 45 patients who received the same standard of care in the early postoperative period, including analgesics, local antibacterial ointments (Levomekol, etc.), and rectal suppositories (Relief Pro, etc.).

Results: In the early postoperative period, in the patients who received non-drug rehabilitation program, the pain was significantly less intensive, and it relieved faster after surgery, which indicated a strong analgesic effect of the rehabilitation program. Patients in the control group received analgesics (including narcotic drugs) for pain control in 68.9% of cases. Duration of postoperative incapacity for work in the main group patients was 12.9±2.4 days vs. 24.1±2.3 days in the control group patients (p<0.001). The analysis of the quality of life in the early and the late postoperative period by SF-36 scale showed a significant difference between the groups according to the physical health component and psychological component both in the early and in the late postoperative period (after six months), which indicates the higher quality of life in the main group patients. Assessment of the late period quality of life using the I. Yu. Alimzhanova and Yu.M. Sheptunov questionnaire showed good results in 43 (95.6%) patients of the main group. Only in 2 (4.4%) main group patients, anal stenosis was observed. Good results were shown in 38 (84.58%) control group patients. Seven patients had complications: cicatricial anal stenosis (5 [11.1%] patients) and pararectal fistulas (2 [4.4%] patients); in 3 (42.9%) of these 7 patients a persistent pain syndrome was developed.

Conclusions: Introduction of the rehabilitation program in the early postoperative period after hemorrhoidectomy contributes to faster relief of pain and other signs and symptoms, a significant decrease of average postoperative wound healing time due to acceleration of adequate scar formation (according to ultrasound sonoelastography), improvement of life quality, reduction of hospital stay, a decrease of incapacity for work duration, and prevention of postoperative complications.

Oncología

Cáncer

Li, Y. and R. Pu (2024), Ozone therapy for breast cancer: an integrative literature review, Integrative Cancer Therapies, volume 23, pp. 1–9, doi: 10.1177/15347354241226667

Conclusion. Ozone therapy is a promising complementary treatment option for breast cancer. As the field of oncology advances, the integration of ozone therapy with conventional cancer treatments could potentially improve outcomes in patients with breast cancer.

Fergusson, J. (2023), A New Zealand case study: The use of ozone therapy as an adjunctive support treatment with radiation therapy in prostate cancer. Case report, Ozone Therapy Global Journal, vol. 13, no. 1, pp. 135-151

Ozone therapy has been shown to be an effective adjunctive therapy with radiation therapy (RT). The aim of this case report is to discuss the benefits of using ozone therapy (OT) as a complementary tool in a patient with prostate cancer who was referred to have RT therapy after a nodal oligo-recurrenceoligo-recurrence of prostate adenocarcinoma cancer was detected after having robotic prostatectomy April 2021.

The patient initially faced twenty-three sessions of radiation therapy (RT) over 5 weeks and chose to also use Goserelin, a novel anti-androgen, with Zytiga (abiraterone) and prednisone. He was concerned about the side effects of RT, short-term and long-side effects such as fatigue, burns, and incontinence.

There is an increase in patients reaching out for different forms of treatment modalities and there is a greater need for physicians to understand about these options. However, the terms associated with adjunctive and alternative therapy has meant confusion and limitations. The use of the umbrella term ‘CAM’ (complementary and alternative therapies) is discussed and how this is used within New Zealand’s legal and medical system with the view it could be more clearly defined, which may result better doctor-patient communication.

We have concluded the use of OT (ozonated saline IV [03SS]), together with minor autohemotherapy [MiAH]) as the primary adjunctive therapy, in this case study proved to be both safe and effective when used in combination with conventional treatment. Fifteen months after RT treatment, the patient is healthy with no side-effects from RT, but the patient had experienced side-effects from the drug therapy which was part of the conventional treatment plan. At the time of this report, the drug therapy still has another six months to conclude.

Clavo, B., et al. (2023), Effects of ozone treatment on health-related quality of life and toxicity induced by radiotherapy and chemotherapy in symptomatic cancer survivors, International Journal of Environmental Research and Public Health, vol. 20, no. 2, p. 1479, doi: 10.3390/ijerph20021479

Background: The continuous improvement in cancer treatment has led to improvement in patients’ survival and a subsequent increase in the number of cancer survivors living with adverse side effects of cancer treatments, sometimes with a high and adverse impact on their health-related quality of life (HRQOL). Side effects of cancer treatments are frequently associated with chronic status of oxidative stress, inflammation, and/or ischemia. The potential for ozone treatment to modulate those processes and improve some of those adverse effects has previously been described. The aim of this study was to evaluate the effect of ozone treatment on the HRQOL and grade of toxicity in symptomatic cancer survivors. (2) Methods: Before and after ozone treatment, we assessed (i) the HRQOL (according to the EQ-5D-5L questionnaire) and (ii) the grade of toxicity (according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute of EEUU (CTCAE v.5.0)) in 26 cancer survivors with chronic side effects of radiotherapy and chemotherapy. (3) Results: There was a significant (p < 0.001) improvement in the EQ-5D-5L index as per the self-reported outcome evaluation of patients’ health status. All the dimensions of the EQ-5D-5L questionnaire (mobility, self-care, activities, pain/discomfort, and anxiety/depression) and the self-evaluation of the health status using the visual analog scale were significantly improved (p < 0.05). The grade of toxicity was also significantly decreased (p < 0.001). (4) Conclusions: In cancer survivors with chronic side effects of cancer treatment, ozone treatment can improve the grade of toxicity and the HRQOL. These results merit additional research. Further studies are ongoing.

Yanchu, Li, et al. (2023), Ozone therapy for high-grade glioma: an overview, Frontiers in Oncology, vol. 13, 6 p., doi: 10.3389/fonc.2023.1161206

In conclusion, ozone therapy represents a promising alternative treatment option for those with cancer and may be a viable régimen for use against gliomas. However, the exact mechanism of action of ozone therapy in gliomas is not yet understood and there is limited evidence in literature. Further basic studies and clinical trials are required to fully evaluate the potential benefits and limitations of ozone therapy.

Infectología

VIH

Cespedes, J., et al. (2018), The immune response behavior in HIV-AIDS patients treated with ozone therapy fot two years, Journal of Ozone Therapy, vol. 2, no. 3, pp. 1-9, doi: 10.7203/jo3t.2.3.2018.11458

HIV continues to be one of the biggest problems for the global public health. The African region is one of the most affected, accounting for almost two thirds of the new infections. Many of them are retroviral medications and multi-therapies aiming to stop the viral replication and maintaining immunological stability, which fail to guarantee the quality of life or enhance the patient’s immunity

Ozone has biological properties, among which the antimicrobial and modulatory effect on the immune response is highlighted, which makes it possible to use it in a complementary way for the treatment of these patients.

We conducted the present study in which the effect of the ozone therapy administered systemically (blood route) is analyzed. We have studied 32 patients to whom we applied Major Autohemotherapy with a protocol of 15 sessions and maintenance every 15 days at 50 μg/mL of concentration; the initial dose was 4,000 μg/mL up to 12,000 μg/mL.

We indicated viral load, CD4 and CD8 counts before and at the end of therapy. The results showed a significant decrease in viral load to undetectable values and an increase of CD4 and CD8 at the end of the 15 sessions, being maintained at 2 years of treatment, thus achieving a permanent activation of the immune system and improving the quality of life of these patients.

Méndez, N., y cols. (2005), Ozonoterapia en sida, Revista Cubana de Investigaciones Biomédicas, vol. 24, núm. 1, pp. 69-71

Se estudió un paciente SIDA IIIc con fatiga, síndrome de mala absorción intestinal, polineuropatía, anemia, con glucosa, creatinina y tiempo de protombina elevados, conteo CD4 en 37 células carga viral en 2 400 000/mL, el cual venía recibiendo un cóctel de triple terapia retroviral, anemia de 10 g/L. Se le administró un ciclo de ozono por vía rectal, a dosis de 5 mg, junto con interferón, factor de transferencia y eritropoyetina recombinante. Al término del tratamiento se le realizó una evaluación final donde se encontró que desaparecieron la fatiga, las diarreas, la deshidratación y la anemia, aumentando 8 kg de peso y se normalizaron los valores de glucosa, creatinina y tiempo de protombina. Después de 3 meses de finalizado el tratamiento con ozono, continuando con la administración ininterrumpida de interferones y una tetraterapia antirretroviral, el conteo CD4 aumentó a 546 con 30 % y la carga viral disminuyó a 1 700/mL. Se valoró el efecto del ozono como inmunomodulador y antimicrobiano potente en pacientes VIH/SIDA.

Lyme

Rowen, R. (2018), Ozone therapy as a primary and sole treatment for acute bacterial infection: case report, Medical Gas Research, vol. 8, no. 3, pp. 121-124, doi: 10.4103/2045-9912.241078

The world is facing a crisis of antibiotic resistance, which impacts every treating physician on the planet. Thousands of patients die yearly in the USA from infections that have failed to respond to anti-infectives. Alarms have been ringing about bacterial infection fatality resurgence, the end of the antibiotic era, a calamity in progress. Ozone therapy has been used in medicine since World War I. However, it is not patentable and has suffered from lack of private source funding for research sufficient to have it accepted by the mainstream. Basic science, both in vivo and in vitro, research has found it to have several effects including modulating the immune system, enhancing circulation, destroying microorganisms including bacteria and viruses, and enhancing oxygen delivery and consumption by the body. This report presents background basic ozone science and a case report of acute bacterial infection – tick bite cellulitis, which immediately responded to ozone therapy as the sole treatment, and which fully resolved within 24-48 hours. Ozone therapy could be considered as an adjunctive or alternative therapy for bacterial infection.

Case report. The patient was a long-term patient of our clinic. He had received ozone from us 3 years before for Lyme disease (without antibiotics), and fully recovered.

Discussion. The CDC reports that recovery from Lyme disease does not confer immunity for a subsequent infection. This patient had recovered from Lyme disease in our clinic with ozone therapy a few years before this tick bite. Hence, it is possible he had Lyme cellulitis, and/or a more acute/common cellulitis bacterial organism.

Hepatitis

Sadek, A., et al. (2024), Effect of ozone gas on viral kinetics and liver histopathology in hepatitis C patients, Journal of Complementary and Integrative Medicine, doi: 10.1515/jcim-2023-0239

Objectives. We examine how well ozone/oxygen gas therapy treats chronic hepatitis C patients with varying degrees of liver fibrosis. Also to study the effect of giving multiple anti-oxidants with the ozone/oxygen gas mixture, to see if this addition would have any additive or synergistic effect.

Subjects and methods . Two hundred and twenty three patients with chronic hepatitis C. Liver biopsies were carried out at after 12 weeks of administering an ozone/oxygen gas mixture.

Results. The mean stage of fibrosis decreased from 1.98 to 1.41 and the mean grade of inflammation decreased from 10.08 to 7.94, both with a p value less than 0.001. After 12 weeks of treatment, mean PCR values increased. No single significant complication was recorded in a total of >9,000 settings of ozone therapy.

Conclusions. Ozone oxygen gas mixture is safe and effective in treatment of hepatic fibrosis due to chronic viral hepatitis C.

Quirúrgico

Tratamiento pre y postquirúrgico

(Prequirúrgico)

International Scientific Committee for Ozone Therapy (2020), Declaración de Madrid sobre la ozonoterapia, 3ª edición, ISCO3, ed., Madrid, pp. 84-85

4.7 Cirugía Oral

4.7.1 Acondicionamiento prequirúrgico

En situaciones donde el estado médico del paciente (diabetes, baja inmunidad, efectos secundarios asociados a medicinas, vejez) podría afectar el proceso de saneamiento o contribuir con complicaciones postoperatorias, un acondicionamiento prequirúrgico podría aliviar tales eventos. El diente o dientes a ser extraídos y sus tejidos periféricos, o incluso toda la boca pueden ser tratados con agua ozonizada y ozono usando el método de aplicación más apropiado para el caso. Si una inyección directa con ozono es elegida, se recomienda aplicarlo en incrementos pequeños (menos de 1 mL) para evitar la posibilidad de introducir grandes cantidades de gas y producir un émbolo dentro de una arteriola.

La frecuencia de la aplicación del ozono debe ser adaptada a la situación clínica del paciente. La administración de ozono parenteral por médicos, puede también contribuir en el acondicionamiento prequirúrgico.

(Postquirúrgico [estas referencias ya estaban antes, en Heridas postquirúrgicas, tal vez es el mismo tema y no vale la pena repetirlo)

Aim: The purpose of the current study was to determine the effectiveness of topical ozone gel application in the management of postextraction wound healing.

Conclusion: The current study came to the conclusion that using ozone gel significantly improves postoperative pain, mouth opening range, and promotes faster wound healing.

Otros tratamientos

Plasma rico en plaquetas

Rabeiro, C., et al. (2023), Treatment of phlebostatic ulcer in the lower limb with platelet-rich plasma activated with ozonecalcium chloride and fibrin membrane. case report, Case Reports, vol. 9, no. 1, 9 p., doi: 10.15446/cr.v9n1.93890

Introducción. La insuficiencia venosa crónica puede tener complicaciones graves como úlceras flebostáticas en las extremidades inferiores. Se ha establecido que la aplicación de plasma rico en plaquetas autólogo (PRP) es una opción segura y eficaz en el tratamiento de las úlceras crónicas, siendo empleado como terapia adyuvante. El uso de PRP ozonizado en el tratamiento de estas úlceras no ha sido muy estudiado, pero clínicamente puede ser una alternativa beneficiosa. Presentación del caso. Mujer de 65 años, diagnosticada con insuficiencia venosa crónica a los 42 años, quien asistió a consulta externa por el servicio de angiología y cirugía vascular por una úlcera flebostática en una de sus extremidades inferiores. La paciente recibió cinco aplicaciones de PRP activado con ozono-cloruro de calcio y membranas de fibrina como tratamiento complementario. A partir de la segunda aplicación se observó una mayor epitelización en el área de la lesión; la cicatrización completa de la úlcera se logró 6 semanas después de finalizado el tratamiento. No se registraron reacciones adversas graves y la paciente refirió una disminución del dolor y mejoría en la realización de actividad física. Conclusiones. La aplicación local de PRP activado con ozono-cloruro de calcio y membranas de fibrina resultó ser una intervención útil para el tratamiento de la úlcera flebostática en el miembro inferior de la paciente reportada, ya que este estimuló la epitelización y cierre de las heridas, lo cual le mejoró la calidad de vida.

Inguscio, C., et al. (2023), Ozone and procaine increase secretion of platelet-derived factors in platelet-rich plasma, European Journal of Histochemistry, vol. 67, no. 4, 3879, pp. 241-251, doi: 10.4081/ejh.2023.3879

Platelet-rich plasma (PRP) is gaining more and more attention in regenerative medicine as an innovative and efficient therapeutic approach. The regenerative properties of PRP rely on the numerous bioactive molecules released by the platelets: growth factors are involved in proliferation and differentiation of endothelial cells and fibroblasts, angiogenesis and extracellular matrix formation, while cytokines are mainly involved in immune cell recruitment and inflammation modulation. Attempts are ongoing to improve the therapeutic potential of PRP by combining it with agents able to promote regenerative processes. Two interesting candidates are ozone, administered at low doses as gaseous oxygen-ozone mixtures, and procaine. In the present study, we investigated the effects induced on platelets by the in vitro treatment of PRP with ozone or procaine, or both. We combined transmission electron microscopy to obtain information on platelet modifications and bioanalytical assays to quantify the secreted factors. The results demonstrate that, although platelets were already activated by the procedure to prepare PRP, both ozone and procaine induced differential morpho-functional modifications in platelets resulting in an increased release of factors. In detail, ozone induced an increase in surface protrusions and open canalicular system dilation suggestive of a marked α-granule release, while procaine caused a decrease in surface protrusions and open canalicular system dilation but a remarkable increase in microvesicle release suggestive of high secretory activity. Consistently, nine of the thirteen platelet-derived factors analysed in the PRP serum significantly increased after treatment with ozone and/or procaine. Therefore, ozone and procaine proved to have a remarkable stimulating potential without causing any damage to platelets, probably because they act through physiological, although different, secretory pathways.