How Ozone Therapy Works: The Science in Plain Words

It is the question we are asked more than any other. Ozone is a gas that lasts only seconds once it touches the body. So how can a few minutes of it, a few times a week, change how someone feels for weeks afterwards?

This page explains that message in plain words: what it is, what it switches on, and why a small dose does more good than a large one.

The short version

Everything else on this page is detail on those four steps.

1. Ozone does its work in seconds, then it is gone

Ozone is three oxygen atoms where ordinary oxygen has two. That third atom makes it highly reactive, and the body's fluids are full of things for it to react with - antioxidants such as vitamin C and uric acid, and the healthy unsaturated fats carried in plasma and cell membranes.^1,2

When researchers at the University of Siena bubbled ozone through human blood, it was completely used up within five minutes.² None was left to travel anywhere. Ozone does not even get inside cells - it reacts in the fluid around them.

The same is true at every surface ozone touches. In rectal insufflation, as Professor Velio Bocci described it, ozone dissolves immediately in the film of water covering the bowel lining and reacts there.¹

2. What travels is the message

That instant reaction produces two kinds of messenger molecule:^1,2

• Hydrogen peroxide - the early messenger. It slips into nearby cells, delivers its signal and is broken down to water within moments.
• Lipid oxidation products - the late messengers, sometimes called ozone peroxides. These are tiny fragments formed when ozone meets unsaturated fats. They hitch a ride on the blood protein albumin and are carried around the body.

Your body makes both of these naturally, every day, as part of normal signalling. Medical ozone simply produces a small, measured pulse of them.

With rectal insufflation, the late messengers are absorbed through the bowel wall into the lymph and the small veins, pass through the liver, and go on into the general circulation.^1,11 This is why a treatment given in one place has effects throughout the body.

3. The message switches on your own defences

Inside almost every cell sits a protein called Nrf2 - think of it as the master switch for the cell's protective systems. Normally it is held in the "off" position. A mild oxidative signal releases it, and it moves into the cell nucleus and turns on a whole family of protective genes at once.⁴

The list of what it switches on is long: superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, haem oxygenase-1 and more. These are the body's own antioxidant and detoxifying enzymes - far more powerful than any antioxidant you can swallow, because each enzyme molecule neutralises thousands of free radicals, not just one.^3,4

At the same time, the inflammatory side is turned down. Levels of the inflammatory messengers TNF-alpha, IL-1 beta and IL-6 fall.³

This is not only laboratory theory. It has been measured in people:

4. The exercise principle

If a small oxidative stress sounds like an odd thing to want, consider exercise. A run produces a burst of free radicals and a measurable, temporary stress on the body. Nobody concludes from this that running is harmful - because the body's response to that stress is what makes you fitter. The same is true in reverse: push to exhaustion day after day without recovery and the stress outruns the body's ability to adapt.

Scientists call this pattern hormesis: a small dose of a stressor produces a benefit that a large dose would not. Professor Bocci and Dr Masaru Sagai drew exactly this comparison for ozone - a brief, calculated oxidative stress that trains the body's defences, then disappears.^1,2

The response to a single session fades. Repeated sessions build an adaptation - which is why ozone is used in courses and cycles rather than as a one-off. Researchers call this ozone preconditioning, and you can read more in Ozone Preconditioning: Waking up the dragon.

5. What people notice, and the biology behind it

The antioxidant switch is the heart of it. Six other effects follow from the same messengers, and they line up closely with what our customers tell us they feel.

6. On the surface, ozone also works directly

Everything above describes systemic ozone - insufflation, or the blood procedures used in clinics. On skin, gums, wounds and the gut lining there is a second, simpler mechanism.

It is the same principle you see when a stubborn wound finally starts to heal: fewer harmful microbes, less inflammation, better blood supply, and the tissue's own repair systems switched on. It is also the one situation where the dose rule runs the other way - see the exception in section 7.

7. Why less is more

Because ozone works as a signal, the dose has a sweet spot.

• Too little and the body's circulating antioxidants mop it up before any message is sent. Nothing happens.
• The right amount sends a clear signal, the defences switch on, and the stress is over in minutes.
• Too much overwhelms the defences it is meant to train. Early clinics that used very high concentrations got poor results for exactly this reason.³

This is the low-dose ozone concept that modern ozone therapy is built on, set out by Dr Renate Viebahn-Hänsler and Professor Olga León Fernández, and it is the basis of the dose ranges in the Madrid Declaration on Ozone Therapy.^3,11 Within that range the Declaration sets low, medium and high levels for different purposes, and its rule for systemic treatment is Professor Bocci's: “start low and go slow”. It is also why a properly calibrated generator matters - you need to know what concentration you are actually delivering. Read our summary of the low-dose ozone concept.

8. Why the clinic route and the home route work the same way

Once you know that ozone gas itself never circulates - only the messengers it creates do^1,2 - the difference between the routes shrinks. Viebahn-Hänsler and León Fernández describe both as systemic applications working through the same biochemistry, and note that rectal insufflation is simple, low-cost and practically free of adverse reactions.^3,10

The Madrid Declaration treats all three as systemic routes. It describes rectal insufflation as reaching doses similar to those used for autohaemotherapy, and rates vaginal insufflation as more effective than either.¹¹ The rheumatoid arthritis and diabetes trials above both used rectal insufflation.

If you would like to see what a home setup involves, our home ozone therapy bundles page lays out the options, and our fibromyalgia research review shows how this plays out in one condition.

9. The one place ozone gas must never go

This is about ozone gas. Breathing the vapour from ozone that has been bubbled through olive oil is a different thing. The ozone reacts with the oil on the way through, and what comes out the other side is no longer ozone gas but a vapour of oil-derived compounds - the Madrid Declaration calls them volatile organic compounds generated by ozone, and deals with them separately from ozone inhalation.¹¹ The same distinction applies to nebulised ozonated glycerine: what is breathed is a fine mist of the ozonated product, not ozone gas. The Declaration notes that clinical research on these vapours is still limited. Our video guide shows how it is done: Breathing Ozonated Oil (BOO).

Ozone therapy is not suitable for everyone. The Madrid Declaration lists the contraindications, including G6PD deficiency (favism), uncontrolled hyperthyroidism, severe clotting disorders and a recent heart attack - the full list is in our fibromyalgia research review. We follow the guidelines of the International Scientific Committee of Ozone Therapy (ISCO3). If you are managing a health condition, we encourage you to work alongside your healthcare practitioner.

Not sure whether ozone suits your situation? Call or email us. We are always happy to talk it through.

Related reading

• Ozone Preconditioning: Waking up the dragon
• The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action
• Ozone Therapy: An Overview of Pharmacodynamics, Current Research, and Clinical Utility
• The Role of Mitochondria in Ozone Therapy
• Rectal Insufflation vs Major Autohaemotherapy: a comparative review
• Ozone therapy, gut microbiota and irritable bowel syndrome

References

1. Sagai M, Bocci V. Mechanisms of action involved in ozone therapy: is healing induced via a mild oxidative stress? Medical Gas Research 2011;1:29. Read our summary.
2. Bocci V, Zanardi I, Travagli V. Ozone acting on human blood yields a hormetic dose-response relationship. Journal of Translational Medicine 2011;9:66. Read our summary.
3. Viebahn-Hänsler R, León Fernández OS. Ozone in medicine. The low-dose ozone concept and its basic biochemical mechanisms of action in chronic inflammatory diseases. International Journal of Molecular Sciences 2021;22:7890. Read our summary.
4. Galiè M, Covi V, Tabaracci G, Malatesta M. The role of Nrf2 in the antioxidant cellular response to medical ozone exposure. International Journal of Molecular Sciences 2019;20:4009. Read our summary.
5. León Fernández OS, Viebahn-Hänsler R, López Cabreja G, et al. Medical ozone increases methotrexate clinical response and improves cellular redox balance in patients with rheumatoid arthritis. European Journal of Pharmacology 2016;789:313-318. Read our summary.
6. Martínez-Sánchez G, Al-Dalain SM, Menéndez S, et al. Therapeutic efficacy of ozone in patients with diabetic foot. European Journal of Pharmacology 2005;523:151-161. Read our summary.
7. Giunta R, Coppola A, Luongo C, et al. Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease. Annals of Hematology 2001;80:745-748. Read our summary.
8. Clavo B, Pérez JL, López L, et al. Effect of ozone therapy on muscle oxygenation. Journal of Alternative and Complementary Medicine 2003;9:251-256. Read our summary.
9. Mallayeva RM. Ozone therapy and gut microbiota in constipation-predominant irritable bowel syndrome. Modern Issues of Biomedicine 2018;2(1):108-114. Read our summary.
10. Viebahn-Hänsler R, León Fernández OS, Fahmy Z. Ozone in medicine: clinical evaluation and evidence classification of the systemic ozone applications, major autohemotherapy and rectal insufflation. Ozone: Science & Engineering 2016;38:322-345. Read our summary.
11. ISCO3. Madrid Declaration on Ozone Therapy, 4th edition. International Scientific Committee of Ozone Therapy, 2025. Sections 1.6, 1.9, 2, 2.1, 3.5, 3.6, 4.10 and 16.1. isco3.org
12. Costanzo M, Cisterna B, Vella A, et al. Low ozone concentrations stimulate cytoskeletal organization, mitochondrial activity and nuclear transcription. European Journal of Histochemistry 2015;59:2515. Read our summary.