Translation of the French article published on the ASNFD website. The statements and perspective of the source text have been retained.
History, practices and therapeutic perspectives
Introduction
Ozone therapy uses the oxidising properties of the triatomic molecule O₃ and is among the most controversial and fascinating alternative therapeutic approaches of our time. This unstable molecule, naturally present in the stratosphere where it protects us from ultraviolet radiation, has had surprising medical applications for more than a century. From early oxygen injections and Tesla’s innovations to modern integrative-medicine protocols, ozone has followed a remarkable scientific path between therapeutic promise and medical scepticism. By exploiting ozone’s oxidative potential to stimulate cellular defences and improve tissue oxygenation, the therapy attracts increasing interest in conventional and naturopathic settings. Its eventful history, marked by promising discoveries and persistent controversy, deserves close examination to understand its present place in modern treatment.
History and development
Beginnings: from oxygen to ozone
The history has roots in early nineteenth-century experiments with therapeutic oxygen. In 1840 German chemist Christian Friedrich Schönbein discovered ozone and identified its distinctive oxidising properties. The discovery opened therapeutic possibilities, although medical applications came decades later. Early therapeutic oxygen experiments date to the 1860s, when doctors injected pure oxygen for various conditions. These empirical approaches laid conceptual foundations for subsequent ozone therapy. Practitioners reported benefits for circulation and general vitality without understanding the underlying physiology.
The Tesla era and technological innovation
Inventor and electrical engineer Nikola Tesla played a decisive role in the late nineteenth century. In 1896 he obtained patent 568,177 for an ozone generator using high-frequency electrical discharges. It described ozone generation through discharges in atmospheric oxygen and enabled controlled, standardised medical ozone production in sufficient quantities for systematic therapeutic use. Tesla also experimented with effects on the human body and recorded observations in personal notebooks. His approach combined scientific rigour with forward-looking insight into potential medical applications of ozone’s electrochemical properties. His work influenced contemporary doctors, particularly in Europe, where use became more systematic.
Pioneers
Several pioneers established scientific and clinical foundations. Christian Friedrich Schönbein (1799-1868), who discovered ozone in 1840, provided the theoretical basis through research into oxidation. Austrian surgeon Erwin Payr (1871-1946) was among the first to use ozone systematically in clinical medicine; from 1906 he developed protocols for surgical infections and gangrenous wounds. His publications documented antimicrobial effectiveness and early safety standards.
E. A. Fisch (1899-1966) developed more refined administration techniques and investigated cellular mechanisms, helping establish modern ozone therapy. Joachim Hänsler (1908-1981) developed early precision medical generators, enabling exact, reproducible dosing essential to rigorous clinical development. Hans Wolff (1927-1980) established standardised clinical protocols and trained a new generation of practitioners. His work on doses and administration routes underpins modern practice.
European development and early clinical applications
Europe became the centre of clinical development in the early twentieth century. In Germany, Dr Ernst Payr began using ozone for surgical infections in 1906. Promising wound-disinfection and gangrene-prevention results attracted international attention. During the First World War, German and French doctors used ozone on war wounds, particularly against anaerobic infections devastating trench soldiers. This period marked a European golden age, with standardised protocols and specialist training. Specialist centres appeared in Germany, Austria and Switzerland in the 1920s and 1930s. Pioneering doctors, including future Nobel laureate Otto Warburg, investigated ozone’s effects on cellular metabolism and laid theoretical foundations for modern understanding.
Mechanisms and scientific foundations
Ozone biochemistry in the body
Ozone consists of three oxygen atoms and acts through complex biochemical mechanisms. Unlike molecular oxygen O₂, it has a high redox potential and distinctive biological properties. Contact with biological fluids rapidly breaks it down into oxygen and reactive oxygen species (ROS), initiating a cascade of beneficial cellular reactions. Its principal mechanism is controlled oxidative stress, or hormesis, which activates endogenous antioxidants including glutathione peroxidase, catalase and superoxide dismutase. This enzyme activation strengthens cellular defences and resistance to pathological stresses. Ozone also stimulates mitochondrial ATP production, improves cellular energy efficiency and modulates genes involved in repair and immunity, contributing to fundamental physiological functions.
Effects on the immune system
Ozone therapy has marked immunomodulatory effects, stimulating immunity at low doses and suppressing it at high doses. This biphasic property allows adaptation to individual pathological needs. Controlled exposure stimulates regulatory cytokines including interferon gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor alpha (TNF-α). These strengthen T lymphocytes, natural killer cells and macrophages, supporting responses to infection and tumour processes. Ozone modulates the balance between pro-inflammatory M1 macrophages producing IL-12 and anti-inflammatory M2 macrophages producing IL-10. This fine regulation supports inflammatory responses in infection and anti-inflammatory responses in autoimmune disease. It also influences immunoglobulins, particularly IgG and IgM, strengthening humoral immunity, resistance to recurrent infections and responses to opportunistic pathogens.
Healing and tissue regeneration
Ozone therapy shows notable effects on healing and regeneration, especially relevant to chronic wounds and degenerative conditions. It stimulates myofibroblast proliferation and collagen production, essential to repair. Neovascularisation is described as a particularly striking effect. Ozone promotes growth-factor release, notably VEGF, TGF-β, FGF-2 and PDGF. This angiogenic cascade favours new blood-vessel formation and improves nutrition and oxygenation of repairing tissues. These properties are presented as explaining effectiveness in diabetic ulcers, atopic wounds, dermatitis, psoriasis and chronic vulval lesions. Antimicrobial action, vascular stimulation and cellular repair create an optimal biological environment for healing.
Toxicity and therapeutic window
Understanding toxicity is crucial to safe therapeutic use. At therapeutic doses, ozone activates beneficial Nrf2 pathways while controlling inflammation through NF-κB modulation. Excessive doses, however, may produce harmful oxidative stress, pro-inflammatory mediators COX2 and PGE₂, and cellular toxicity. Hydrogen peroxide (H₂O₂) production at the application site is a key mechanism: it acts as a second messenger conveying beneficial effects to surrounding tissue while maintaining local antimicrobial activity. Precise management of H₂O₂ production largely determines therapeutic success and adverse-effect prevention.
Therapeutic applications and medical practice
Conventional medicine
Ozone therapy has specific, well-documented applications in conventional medicine, particularly in European countries where it is recognised as an adjunct. Germany, Austria and Italy have developed rigorous clinical protocols and specialist medical training, integrating it into standard practice. Oncology is described as especially promising. Used alongside chemotherapy and radiotherapy, ozone therapy may improve effectiveness and reduce adverse effects. Clinical studies show better quality of life and sometimes longer survival in certain cancers. In infectious disease, ozone shows activity against viruses, bacteria, fungi and parasites. This broad antimicrobial property makes it valuable for infections resistant to conventional antibiotics. Hospital protocols use it for wound disinfection, chronic ulcers and healthcare-associated infections.
Cardiology and vascular conditions
Cardiological use rests on beneficial effects on circulation and cardiac metabolism. Patients with angina, congestive heart failure and peripheral arterial disease show significant clinical improvements. Protocols generally use major autohaemotherapy: the patient’s blood is collected, mixed with medical ozone and reinfused. This improves myocardial oxygenation, reduces vascular inflammation and optimises endothelial function. Reported results include fewer angina episodes, better exercise tolerance and lower cardiovascular inflammatory markers. In peripheral arterial disease, ozone therapy is particularly effective for intermittent claudication and ischaemic ulcer healing. Better microcirculation improves limb perfusion and reduces amputation risk in diabetic patients.
Aesthetic and anti-ageing medicine
Increasing use draws on antioxidant and regenerative properties. Skin treatments improve texture, reduce ageing signs and stimulate natural collagen. Protocols include topical ozonated oils, subcutaneous ozone insufflation and localised ozone baths. These stimulate skin circulation, regeneration and elasticity, with visible wrinkle reduction, brighter complexion and fewer imperfections. Systemic ozone therapy also contributes to anti-ageing programmes by improving overall cellular oxygenation, stimulating endogenous antioxidants and optimising energy metabolism. This holistic approach supports vitality, physical energy and resistance to age-related oxidative stress.
Naturopathy and integrative medicine
Naturopathic philosophy
Ozone therapy fits the naturopathic principle of vis medicatrix naturae, nature’s healing power. Practitioners regard ozone as a catalyst for self-healing rather than an isolated symptomatic treatment. A holistic programme combines it with nutrition, herbal medicine, exercise and stress management. Such synergistic integration optimises benefits and minimises adverse-effect risks. Naturopaths use ozone therapy for energy imbalances, liver and intestinal detoxification and natural immune support. This preventive approach seeks physiological balance and prevention of chronic conditions.
Specific protocols
Naturopathic protocols are individualised and gradual, adapting to constitution, biological background and medical history to ensure optimal effectiveness and excellent tolerance. Rectal ozone insufflation is among the most used techniques. Described as simple and non-invasive, it enables gradual systemic absorption while benefiting intestinal flora. Practitioners use it for dysbiosis, chronic inflammation and immune disorders. Ozone baths are also favoured for relaxation and ease of application, combining traditional hydrotherapy with ozone’s therapeutic properties.
Detoxification and drainage
Ozone therapy occupies a central place in naturopathic detoxification and elimination programmes. It stimulates liver activity, improves renal filtration and optimises toxin elimination through lungs and skin. Protocols generally combine it with liver-supporting herbs, lymphatic drainage and specific nutritional programmes, seeking deep cleansing and restoration of biological balance. Ozone also facilitates elimination of heavy metals and environmental pollutants. Its natural chelating action and stimulation of endogenous detoxification are presented as valuable in chronic intoxication.
Future perspectives and current research
Contemporary clinical research
Research is experiencing renewed activity through rigorous methods and increasingly sophisticated analytical technologies. Randomised controlled studies are multiplying and providing robust evidence of therapeutic effectiveness. Current work seeks detailed molecular understanding. Molecular biology, genomics and proteomics identify activated signalling pathways and help optimise protocols for individual biological profiles. Personalised medicine opens new possibilities: specific biomarkers now allow prediction of individual responses and adaptation of doses and protocols to genetic and metabolic profiles.
Technological innovation
New-generation generators offer greater precision and safety, real-time monitoring, automated protocols and intuitive interfaces, widening access while ensuring safe use. Nanotechnology offers possibilities for targeted administration: ozone-carrying nanoparticles could deliver specifically to pathological tissues, improving effectiveness while limiting effects on healthy tissues. Artificial intelligence in treatment planning is another major advance. Machine-learning algorithms analyse clinical, biological and genetic data to propose personalised protocols and predict outcomes with unprecedented precision.
Conclusion
From early oxygen experiments to Tesla’s innovations, ozone therapy has a rich scientific history and is presented today as a promising, evolving modality. Diverse discoveries and clinical applications illustrate considerable potential across many conditions. Its gradual integration into conventional medicine, alongside naturopathic and integrative development, illustrates both breadth and complementarity. The convergence of empirical traditions and modern research offers encouraging prospects.
Antibiotic resistance, rising chronic disease and the search for less invasive treatments position ozone therapy as a response to contemporary needs. Its favourable safety profile, broad activity and stimulation of natural healing make it a valuable addition to available therapies. Its future depends on continued rigorous trials, technological innovation and qualified training. These should improve understanding, optimise protocols and increase recognition within twenty-first-century medicine. With its historical legacy and promising prospects, ozone therapy is thus presented as a modern, scientifically grounded and clinically effective approach that I hope will play a growing role in comprehensive human healthcare.
Fabrice Leu ND