Table of Contents    
Year : 2011  |  Volume : 2  |  Issue : 1  |  Page : 66-70  

Ozone therapy: A clinical review

Viveknand Education Society's, College of Pharmacy, Mumbai, India

Date of Web Publication25-Jun-2011

Correspondence Address:
A M Elvis
Vivekanand Education Societys; College of Pharmacy, Hashu Advani Memorial Complex, Behind Collector's Colony, Chembur [E], Mumbai-400 074
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-9668.82319

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Ozone (O 3 ) gas discovered in the mid-nineteenth century is a molecule consisting of three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. Although O 3 has dangerous effects, yet researchers believe it has many therapeutic effects. Ozone therapy has been utilized and heavily studied for more than a century. Its effects are proven, consistent, safe and with minimal and preventable side effects. Medical O 3 is used to disinfect and treat disease. Mechanism of actions is by inactivation of bacteria, viruses, fungi, yeast and protozoa, stimulation of oxygen metabolism, activation of the immune system. Medication forms in a gaseous state are somewhat unusual, and it is for this reason that special application techniques have had to be developed for the safe use of O 3 . In local applications as in the treatment of external wounds, its application in the form of a transcutaneous O 3 gas bath has established itself as being the most practical and useful method, for example at low (sub-atmospheric) pressure in a closed system guaranteeing no escape of O 3 into the surrounding air. Ozonized water, whose use is particularly known in dental medicine, is optimally applied as a spray or compress. Diseases treated are infected wounds, circulatory disorders, geriatric conditions, macular degeneration, viral diseases, rheumatism/arthritis, cancer, SARS and AIDS.

Keywords: Allodynia, autohemotherapy, lipid ozonation products, ozone

How to cite this article:
Elvis A M, Ekta J S. Ozone therapy: A clinical review. J Nat Sc Biol Med 2011;2:66-70

How to cite this URL:
Elvis A M, Ekta J S. Ozone therapy: A clinical review. J Nat Sc Biol Med [serial online] 2011 [cited 2021 Apr 14];2:66-70. Available from:

   Introduction Top

Ozone (O 3 ), a gas discovered in the mid-nineteenth century, is a molecule consisting of three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. The gas is colorless, acrid in odour and explosive in liquid or solid form. It has a half-life of 40 min at 20°C and about 140 min at 0°C. Its basic function is to protect humans from harmful effects of UV radiation. Ozone occurs at less than 20 μg/m 3 from the Earth's surface at concentrations that are perfectly compatible with life. Although O 3 has dangerous effects, yet researchers believe it has many therapeutic effects. [1],[2],[3] The beginning of precise medical O 3 generators has only recently allowed the mechanisms, action and possible toxicity of O 3 to be evaluated by clinical trials. [2] Ozone has a capacity to oxidize organic compounds, [4] and has well-known toxic effects on the respiratory tract when present in smog. [5],[6] In medical use the gas produced from medical grade oxygen is administered in precise therapeutic doses, and never via inhalation, and advocates that it has excellent health benefits in dental caries, decrease blood cholesterol and stimulation of antioxidative responses, modifies oxygenation in resting muscle and is used in complementary treatment of hypoxic and ischemic syndromes. [7],[8],[9],[10]

   History of Ozone Therapy Top

Ozone therapy has been utilized and extensively studied for many decades altogether. Its effects are proven, consistent and with minimal side effects. Medical O 3 , used to disinfect and treat disease, has been around for over 150 years. Used to treat infections, wounds and multiple diseases, O 3 's effectiveness has been well-documented. It has been used to disinfect drinking water before the turn of the last century. Ozone was known to treat as many as 114 diseases. [11] Ozone therapy has been in use since the 1800s and in 1896 the genius Nikola Tesla patented the first O 3 generator in the US, later forming the 'Tesla Ozone Company." [12] During the first world war (1914-18) doctors familiar with O 3 's antibacterial properties, and with few other medical resources available to them applied it topically to infected wounds and discovered O 3 not only remedied infection, but also had hemodynamic and anti-inflammatory properties. [13] In the late 1980s, reports had emerged that German physicians were successfully treating HIV patients with 03-AHT (Autohemotherapy). There was then no pharmaceutical treatment for HIV and a pandemic was feared, so Canadian authorities authorized the study to test safety and efficacy of 03-AHT in AIDS patients. Ozone had shown promise in in vitro testing. Ozone was seen effective at disinfecting extracorporeal blood samples of HIV; unfortunately for AIDS patients, 03-AHT proved to be an in vivo ineffective treatment [14],[15] [Table 1].
Table 1: The chronological use of ozone in medicine

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   Sars and Ozone Top

Ozone is a naturally occurring energy-rich molecule embodying unique physico-chemical and biological properties suggesting a possible role in the therapy of SARS, either as a monotherapy or, more realistically, as an adjunct to standard treatment regimens. Owing to the excess energy contained within the O 3 molecule, it is theoretically likely that O 3 , unlike organism-specific antiviral options available today, will show effectiveness across the entire genotype and subtype spectrum of SARS. [25]

   Mechanism of Action Top

Inactivation of bacteria, viruses, fungi, yeast and protozoa: Ozone therapy disrupts the integrity of the bacterial cell envelope through oxidation of the phospholipids and lipoproteins. In fungi, O 3 inhibits cell growth at certain stages. With viruses, the O 3 damages the viral capsid and upsets the reproductive cycle by disrupting the virus-to-cell contact with peroxidation. The weak enzyme coatings on cells which make them vulnerable to invasion by viruses make them susceptible to oxidation and elimination from the body, which then replaces them with healthy cells. [26]

Stimulation of oxygen metabolism: Ozone therapy causes an increase in the red blood cell glycolysis rate. This leads to the stimulation of 2,3-diphosphoglycerate which leads to an increase in the amount of oxygen released to the tissues. Ozone activates the Krebs cycle by enhancing oxidative carboxylation of pyruvate, stimulating production of ATP. It also causes a significant reduction in NADH and helps to oxidize cytochrome C. There is a stimulation of production of enzymes which act as free radical scavengers and cell-wall protectors: glutathione peroxidase, catalase and superoxide dismutase. Production of prostacyline, a vasodilator, is also induced by O 3 [Figure 1]. [25]
Figure 1: Action of ozone on RBC Metabolism[27]

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Activation of the immune system: Ozone administered at a concentration of between 30 and 55 μg/cc causes the greatest increase in the production of interferon and the greatest output of tumor necrosis factor and interleukin-2. The production of interleukin-2 launches an entire cascade of subsequent immunological reactions. [27]

Mechanism of action of O 3 on the human lung: Ozone exposure induces a significant mean decrement in vital capacity. It significantly increases mean airway resistance and specific airway resistance but does not change dynamic or static pulmonary compliance or viscous or elastic work. It also significantly reduces maximal transpulmonary pressure. And further more significantly increases respiratory rate and decreased tidal volume. [27]

   Clinical Trials Top

The study to evaluate effect of bimosiamose on O 3 -induced sputum neutrophilia: Biomosiamose is an anti-inflammatory glycomimetic and selectin inhibitor. [28] It is found effective against disease states involving inflammatory cells like for example for asthma. [29] This drug, as per last updation, was in phase 2 trials and being evaluated for its efficacy and safety in treating chronic pulmonary obstructive disease (COPD), the study is sponsored by Revotar Biopharmaceuticals AG and was carried out by NCT00962481 ( Identifier). [30]

Evaluate the effects of the drug (SB-656933-AAA) on the body after a single dose in subjects who have inhaled O 3 : Drug SB-656933-AAA was developed by GlaxoSmithKline which was found to exhibit good activity in treating COPD as well as cystic fibrosis. This action was found to be enhanced by administration of a single dose of O 3 before administration of the aforementioned drug. This drug until latest updated data was in phase 1 stage, study was carried out by NCT00551811. [31]

Intraarticular O 3 therapy for pain control in osteoarthritis of the knee: Ozone is being currently tested for its effectiveness in relieving the pain in patients suffering from osteoarthritis of the knee. The current status of the study is phase 2 which is sponsored by Ben-Gurion University of the Negev and the study being conducted by NCT00832312. [32]

The Effect of Ozone Therapy for Lumbar-Herniated Disc: Ozone is also being evaluated for its efficacy infiltration and its effectiveness in comparison with microdiscectomy in the treatment of lumbar-herniated disc with criteria for surgery. The study is currently in its phase 2 studies, which is sponsored by Kovacs Foundation and trials being carried out by NCT00566007. The study also evaluates the efficacy of infiltration in presence of corticoids, anesthetics, which is being compared by replacing O 3 by oxygen. [33],[34],[35]

   Advantages of Ozone Therapy Top

Diabetic complications are attributed to the oxidative stress in the body, O 3 was found to activate the antioxidant system affecting the level of glycemia. Ozone prevented oxidative stress by normalizing the organic peroxide levels by activating superoxide dismutase. [36],[37] Ozone was found to completely inactivate the HIV in vitro, this action of O 3 was dose-dependent. Concentration used for inactivation was found to be non-cytotoxic. The inactivation was owing to the reduction of the HIV p24 core protein. [38] Ozone was also found to increase the host immunity by increasing the production of cytokine. [39] In an in vitro study, it was observed that O 3 is very effective in reducing the concentrations of Acinetobacter baumannii,  Clostridium difficile Scientific Name Search  methicillin-resistant Staphylococcus aureus in dry as well as wet samples, hence it can be used as a disinfectant. Oxygen/ O 3 mixture was also found to prolong the appearance of arrhythmia induced by potassium chloride, aconitine, etc., in laboratory animals like rats. [40]

   Disadvantages of Ozone Therapy Top

An array of ill-effects are observed owing to the reactivity of O 3 viz oxidation, peroxidation or generation of free radicals and giving rise to cascade of reactions like peroxidation of lipids leading to changes in membrane permeability, [41] lipid ozonation products (LOP) act as signal transducer molecules. [42] The main reason for this being presence of unsaturated fatty acids in both lung lining fluid and pulmonary cell bilayers, O 3 reacts with unsaturated fatty acids to give their specific products i.e., LOP, which activates the lipases triggering the release of endogenous mediators of inflammation. [43] The loss of functional groups in enzymes leading to enzyme inactivation. These reactions further results in cell injury or eventual cell death. Combinations of O 3 and NO 2 occur in photochemical smog, have hazardous effects on lung alveoli and act additively or synergistically. Dietary antioxidants or free radical scavengers like vitamin E, C, etc., can prevent aforementioned effects of O 3 . [44],[45]

In an in vitro study it was observed that arachidonic acid was oxidized in presence to O 3 to give peroxides, viz. arachidonic acid peroxides (AAP), having activity comparable to prostaglandin endoperoxides. These peroxides were fond to show following actions contraction of rabbit aortic strips and rat fundus strips in presence on indomethacin and Vane's mixture of vasoactive hormones at doses comparable to naturally formed prostaglandin peroxides. AAP also caused aggregation of human platelets in platelet-rich plasma, but these effects were not observed in presence of indomethacin and vitamin E, which indicated that these can be used to treat such toxicity of O 3 . [46]

   Recent Development Top

Ozone was effectively used as an antibacterial agent to treat oral infections caused by Actinomyces naeslundii, Lactobacilli casei and Streptococcus mutans. Exposure of about 60 s exhibited 99.9% killing efficiency, but exposure for such a long period showed degradation of saliva proteins. So exposure of 10 s to 30 s was proved effective to kill significant number of bacteria. [47]

A single subcutaneous injection of O 3 in mouse with spared nerve injury of the sciatic nerve was found to decrease the neuropathic pain-type behavior. Mechanism of this action is yet unclear but O 3 was observed to regulate the expression of the genes that play vital role in onset and maintenance of allodynia. [48]

   Acknowlegdement Top

The authors would like to thank Mr. Deepak Ahire, Ex-lecturer of Pharmaceutical Chemistry, V.E.S. College of Pharmacy, for enlightening us with some key points on Ozone Therapy and for successful completion of the article.

   References Top

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Shruti Chhabra,Naveen Chhabra,Avneet Kaur,Niti Gupta
Journal of Maxillofacial and Oral Surgery. 2016;
[Pubmed] | [DOI]
32 Towards the understanding of non-thermal air plasma action: effects on bacteria and fibroblasts
Oleg Lunov,Vitalii Zablotskii,Olexander Churpita,Ales Jäger,Leoš Polívka,Eva Syková,Natalia Terebova,Andrei Kulikov,Šárka Kubinová,Alexandr Dejneka
RSC Adv.. 2016; 6(30): 25286
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33 Potentiometry for the determination of oxidant activity
Kh. Z. Brainina,A. S. Zaharov,M. B. Vidrevich
Anal. Methods. 2016; 8(28): 5667
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34 Dental applications of ozone therapy: A review of literature
Sansriti Tiwari,Alok Avinash,Shashank Katiyar,A. Aarthi Iyer,Suyog Jain
The Saudi Journal for Dental Research. 2016;
[Pubmed] | [DOI]
35 Associations of maternal personal exposure to air pollution on fetal weight and fetoplacental Doppler: a prospective cohort study
Mariana A. Carvalho,Lisandra S. Bernardes,Karen Hettfleisch,Luciana D.M. Pastro,Sandra E. Vieira,Silvia R.D.M. Saldiva,Paulo H.N. Saldiva,Rossana P.V. Francisco
Reproductive Toxicology. 2016;
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36 A superhydrophilic titanium implant functionalized by ozone gas modulates bone marrow cell and macrophage responses
Ulrike Sunarso,Riki Toita,Kanji Tsuru,Kunio Ishikawa
Journal of Materials Science: Materials in Medicine. 2016; 27(8)
[Pubmed] | [DOI]
37 Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis
Sello Lebohang Manoto,Makwese Johaness Maepa,Shirley Keolebogile Motaung
Saudi Journal of Biological Sciences. 2016;
[Pubmed] | [DOI]
38 Major Ozonated Autohemotherapy Preconditioning Ameliorates Kidney Ischemia-Reperfusion Injury
Eyup Burak Sancak,Hakan Turkön,Selma Çukur,Sevilay Erimsah,Alpaslan Akbas,Murat Tolga Gulpinar,Huseyin Toman,Hasan Sahin,Metehan Uzun
Inflammation. 2016; 39(1): 209
[Pubmed] | [DOI]
39 AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats
Lijuan Lu,Cailong Pan,Lu Chen,Liang Hu,Chaoyu Wang,Yuan Han,Yanjing Yang,Zhixiang Cheng,Wen-Tao Liu
Journal of Molecular Cell Biology. 2016;
[Pubmed] | [DOI]
40 Ozon- und Sauerstofftherapie in der Onkologie — kritische Bestandsaufnahme
Bernhard Ost
gynäkologie + geburtshilfe. 2016; 21(S1): 22
[Pubmed] | [DOI]
41 Effectiveness of a Short-Term Treatment of Oxygen-Ozone Therapy into Healing in a Posttraumatic Wound
Irene Degli Agosti,Elena Ginelli,Bruno Mazzacane,Gabriella Peroni,Sandra Bianco,Fabio Guerriero,Giovanni Ricevuti,Simone Perna,Mariangela Rondanelli
Case Reports in Medicine. 2016; 2016: 1
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42 Does topical ozone therapy improve patient comfort after surgical removal of impacted mandibular third molar? - A randomized controlled trial
S. Varun Prasad,P. Elavenil,V.B. Krishnakumar Raja,Gopi Gayathri
Journal of Oral and Maxillofacial Surgery. 2016;
[Pubmed] | [DOI]
43 Ozone therapy for treating foot ulcers in people with diabetes
Jian Liu,Peng Zhang,Jing Tian,Lun Li,Jun Li,Jin Hui Tian,KeHu Yang
Cochrane Database of Systematic Reviews. 2015;
[Pubmed] | [DOI]
44 Effects of ozonated autohemotherapy on the antioxidant capacity of Thoroughbred horses
Journal of Veterinary Medical Science. 2015; 77(12): 1647
[Pubmed] | [DOI]
45 Anton syndrome during oxygen-ozone therapy
Sema Avci,Fatih Büyükcam,Ömer Faruk Demir,Seda Özkan
The American Journal of Emergency Medicine. 2015; 33(6): 856.e1
[Pubmed] | [DOI]
46 Prophylaxis and therapeutic potential of ozone in buiatrics: Current knowledge
Dražen Đuricic,Hrvoje Valpotic,Marko Samardžija
Animal Reproduction Science. 2015; 159: 1
[Pubmed] | [DOI]
47 Daily Oxygen/O3Treatment Reduces Muscular Fatigue and Improves Cardiac Performance in Rats Subjected to Prolonged High Intensity Physical Exercise
C. Di Filippo,M. C. Trotta,R. Maisto,D. Siniscalco,M. Luongo,L. Mascolo,R. Alfano,M. Accardo,C. Rossi,F. Ferraraccio,M. D’Amico
Oxidative Medicine and Cellular Longevity. 2015; 2015: 1
[Pubmed] | [DOI]
48 Non-Thermal Atmospheric-Pressure Plasma Possible Application in Wound Healing
Beate Haertel,Thomas von Woedtke,Klaus-Dieter Weltmann,Ulrike Lindequist
Biomolecules & Therapeutics. 2014; 22(6): 477
[Pubmed] | [DOI]
49 The effects of air pollution on adverse birth outcomes
Sandie Ha,Hui Hu,Dikea Roussos-Ross,Kan Haidong,Jeffrey Roth,Xiaohui Xu
Environmental Research. 2014; 134: 198
[Pubmed] | [DOI]
50 Ozone (O3) elicits neurotoxicity in spinal cord neurons (SCNs) by inducing ER Ca2+ release and activating the CaMKII/MAPK signaling pathway
Yun Li,Xiaowen Lin,XueJun Zhao,Juntian Xie,Wang JunNan,Tao Sun,Zhijian Fu
Toxicology and Applied Pharmacology. 2014;
[Pubmed] | [DOI]
51 Ozone therapy as an adjunct to vancomycin enhances bacterial elimination in methicillin resistant Staphylococcus aureus mediastinitis
Senol Gulmen,Tunay Kurtoglu,Ibrahim Meteoglu,Selcuk Kaya,Huseyin Okutan
Journal of Surgical Research. 2013; 185(1): 64
[Pubmed] | [DOI]
52 Neurological symptoms following exposure to ozone
Dolores Vilas Rolán,Marta Milŕ Lopez,Gemma Cuberas-Borrós,Juan Luis Becerra Cuńat,José Vicente Hervás,Anna Massuet Vilamajó,Domingo Escudero
Journal of Neurology. 2012; 259(12): 2740
[Pubmed] | [DOI]
53 Neurological symptoms following exposure to ozone
Rolán, D.V. and Lopez, M.M. and Cuberas-Borrós, G. and Cunat, J.L.B. and Hervás, J.V. and Vilamajo, A.M. and Escudero, D.
Journal of Neurology. 2012; 259(12): 2740-2742


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