Ozone Therapy Conclusions by Professor Velio Bocci – 2009

Ozone. A New Medical Drug 2nd Edition

Ozone Applications

Major Ozone Autohemotherapy – A volume of blood is drawn from an arm vein, exposed to Oxygen/Ozone for at least 5 minutes with gentle mixing and re-infused either IV (major AHT) or Intramuscular (IM) (minor AHT).

This procedure may only be performed by those that have the necessary qualifications, namely Doctors or Nurses.

Minor Autohemotherapy – A volume of blood is drawn and via a two-way stopcock, Oxygen/Ozone is added to the blood. This is mixed very vigorously and foam is formed. This is then injected back into the buttocks in one location only. This can be done with multiple injections and repeated 2 – 3 times weekly.

Bio-oxidative Therapy with Hydrogen Peroxide dissolved in the Isotonic Glucose or Saline Solution – “Now I must strongly recommend to avoid the use of Ozonated saline owing to inherent toxicity or/and doubtful pharmacologic activity” V Bocci

Rectal Insufflation of Oxygen-Ozone (RI) – RI should be done after defecation or after an enema, when the rectal ampulla is empty. Prof Bocci has stated that this kind of therapy can be done for 20-30 minutes at a time as the body can expel the gas. This type of treatment must be done very slowly and it is something that people can do on themselves at home.

Quasi-Total Body Exposure to Oxygen-Ozone (BOEX) or Hyperthermia Ozone Therapy –

Is ozone as toxic for the skin as it is for the respiratory mucosa?

“Both Ozone treatment and UV-irradiation of epidermal layers of murine and human skin cause peroxidation and depletion of vitamins C and E. It has also been shown that these oxidizing agents, hence Reactive Oxygen Species (ROS) and Lipid Oxidation Products (LOP) activate Nuclear factor Kappa B (NFKB) and activator protein 1, but that alpha-lipoic acid, n-acetyl-cysteine, Thioredoxin and Selenium can inhibit the activation to a large extent and induce adaptive protection, such as over-expression of Manganese-superoxide dismutase and Glutathione peroxidise as a salutary response to oxidative damage.

It is clear that the skin has a multiform antioxidant defence system, far more potent than that present in Respiratory tract lining fluids and that it cannot be overwhelmed provided the attack by ozone or UV irradiation is not too harsh. These findings lend support to the empirical observation that during topical ozone therapy of necrotic ulcers, we have never noticed damage to normal skin. Moreover, during balneotherapy with slightly Ozonated water, no local or generalized untoward effects have been reported.

Are there anatomical-physiological reasons for the relative tolerance of skin to ozone?

Yes, owing to the structure of the skin with the epidermis, the derma and the disposition of the vascular system. The most external layer is the stratum corneum, which is a compressed and tough layer. This “dead layer” is more or less covered by a very dynamic film, containing some proteins, ions, lipids and water, due to the secretion of the eccrine glands. The layers of lipids, produced by sebaceous glands, consists of unusual oily material. This represents the first line of defence against ozone and UV rays. Progressing towards the dermis, there are stratum granulosum, the stratum Malpighi and the proliferating basil layer. The dermis and the subcutaneous tissue contain a very flexible vascular system with a heat exchanger, represented by capillaries and mainly by the venous plexus associates with the opening of arteriovenous shunts. It is able to accommodate up to 30% of the cardiac output so that heat transfer through the skin can increase up to eightfold from a state of total vasoconstriction to extreme vasodilation.

When the skin is exposed to Oxygen-Ozone, do these gases penetrate all the cell layers to reach the dermis and enter the capillaries?

It has been said that Ozone reaches the blood circulation and has a cleansing effect, with the elimination of viruses and toxins. Yet this claim propagated by quacks is not correct and it has only commercial purposes. Only Oxygen and carbon dioxide can move easily through cell membranes. HOWEVER, owing to its dipolar moment and high solubility, ozone dissolves in the superficial water film and reacts immediately with polyunsaturated fatty acids of the sebum, generating reactive Oxygen species, hence H2O2 and an array of Lipid Oxidation products . Therefore it is more likely that ozone does not even reach the phospholipids of the outer corneocytes. However the generated ROS and LOP’s can be partly absorbed and pass through the epidermis, derma and capillary wall to enter both the lymphatic system and the blood stream. Obviously hydrogen peroxide and other ROS have a very short half life and will be quickly reduced.

Does skin vasodilatation enhance the transfer of O2, CO2 ROS and LOP’s?

It certainly does. The “thermal stress” that is easily induced with hyperthermia increases cutaneous capillary perfusion which may increase the “perspiration sensibilis” through activation of sweat glands and may also favour absorption of ROS and LOP’s produced during an ozonated sauna

Prof Bocci and Dr Borrelli did research to evaluate the following aspects:

  • Possible variations of arterial and venous O2 partial pressure, C02 partial pressure, pH, examined before, immediately after and then 0.5, 1 and 24 hours after a period in the sauna cabin in the presence of either Oxygen-ozone or only oxgen.
  • Modifications of body mass, oral temperature, diastolic and systolic blood pressure and ECG pattern.
  • Whether there were any possible variations of peroxidative markers in plasma during and after treatment. In other words we wanted to ascertain whether a 20 minute exposure to ozone of almost the entire cutaneous surface could induce an oxidative stress and if so, if this would be tolerable and lead to a therapeutic benefit.
  • The flow was 1L/min.
  • Steam was generated by a thermostatically controlled heater.
  • The session lasted 20 minutes and the maximum temperature inside the cabin was set between 46 – 50 degrees with humidity of 100%.


  • There was a significant increase in body temperature, which reached a peak at the end of the treatment and declined rapidly thereafter. Maximum oral temperature ranged between
  • 37.5 and 39.3
  • There was a concomitant reduction in body mass (200 – 600g)
  • Blood pressure decreased slightly, but recovered within the next 30 – 60 minutes
  • There was a significant increase of O2 venous partial pressure at the end of the session and for about 1 hour after. This indicated that oxygen had been absorbed via the skin.
  • Values for both erythrocytes (Red Blood Cells) and haematocrit (Precentage of red blood cells) increase immediately after the 20 minute session. They decreased thereafter, probably due to rehydration and were almost normal after 24 hours.
  • There was a significant increase in leukocytes (White Blood Cells), followed by a decrease 1 hour after.
  • The experimental data regarding the plasma levels, modifications of total antioxidant, peroxidation values measured as Thiobarbituric Acid Reactive Sustances (In the Brain) and protein-thiol groups oxidation were surprising:-
  • Antioxidants declined but remained at a substantial level
  • Peroxidation levels increased steeply up to an hour after the end of the session
  • Protein-thiol groups declined during the same period
  • No haemolysis (Red blood cells releasing haemoglobin) was noted at any time
  • Levels of IL-8 (Immune System Reaction) significantly increased 30 minutes after exposure
  • Levels of myeloperoxidase (Preoxidase enzyme) and transforming growth factor either did not change or tented to decrease
  • Plasma levels of hepatic enzymes and creatinine (Renal Function Measurement) remained within the normal range
  • Ozone clearly accounts for the significant linear increase of peroxidation values measured up to an hour after the session


  • Ozone toxicity for the respiratory tract:
  1. The cabin must be tightly closed
  2. The room must be well ventilated
  3. The ozone must be turned off before the client leaves the unit
  • Ozone toxicity for the skin:
  1. We did not observe any acute or chronic toxicity
  • Systemic toxicity of ozone:
  1. We had no direct information on this but as Ozone reacts immediately on the liquid film layered on the cutaneous surface, only some of the generated ROS and LOP’s might be absorbed and enter the circulation. We envisaged that dilution, metabolic breakdown and renal excretion would minimize the increase, if any of LOP’s diluted in the body fluids. Contrary to our expectation, there was a significant increase of circulation LOPs, which continued long after the session, suggesting a steady inflow from the skin prevailing over catabolism. Protein thiol group values showed a consistent decrease, while Total Antioxidant Status values declined only slightly and temporarily. The induced oxidative stress had a brief lifetime and did not cause haemolysis or any modification of important blood parameters. Hepatic enzymes and creatinine plasma levels remained unmodified.
  2. No toxicity after repeated therapy has been noted.
  • None of the volunteers, nor several patients have reported acute or late side effects

Why do the clients feel so good?

This could be attributed to the hyperthermia. We found that the short-term hormonal changes during and after sauna bathing, particularly the described increase of growth hormone and beta endorphin, are quite interesting. Long term sauna bathing helps to lower blood pressure. These changes are brief and can be revisable.

Does Ozone switch on a dangerous oxidative stress?

Although we noticed a remarkable systemic increase of peroxidation, it was transitory, since the levels returned to baseline after 24 hours. We purposefully want to induce an acute oxidative stress in patients, but because we don’t want to override the antioxidant defence system nor cause any toxicity, we must ensure that everything is calculated and transitory. We also want to give precise, atoxic shock to an organism which for various reasons has gone astray. Moreover there is consensus regarding the upregulation of the antioxidant system following repeated but small oxidative shocks.

     Does BOEX/Hyperthermia Ozone have some advantages?

During the treatment there is a loss of 300-500g of water due to intense perspiration, normal for sauna bathing. This loss of water is ridiculously advertised as greatly beneficial because the “body gets rid of oxidised toxins”, in this way. Transitory hyperoxygenation is also considered relevant, but it would be absurd to increase O2 partial pressure through the skin when we could increase them far more simply by breathing oxygen for 1 hour. It is well known that moderate hyperthermia positively modulates the immune system during infection and cancer. On the other hand excessive hyperthermia presents several risks and should be avoided. In other words temperatures and time must be regulated. An initial leukocytosis, followed by a modest leucopenia, was observed after exposure to oxygen-ozone and was probably due to a transient release of IL-8. IL-8 is a chemokine that is released rapidly by leukocytes in blood that has been briefly exposed to Oxygen-ozone.   The simultaneous release of some pro-inflammatory cytokines such as IL-1 may temporarily increase the hyperthermic effect owing to a direct effect on the thermoregulatory centre in the hypothalamus.

What might be the practical usefulness of BOEX and does it have a future?

  • If one uses the standard optimised AHT method, one is able to slowly treat several ailments without any risk to the patient, but venous punctures are necessary.
  • Rectal insufflation is extremely easy to do, very cheap and practically free of risk. Yet it is objected to by some patients and while the delivery of a precise volume of gas is certain, owing to the fecal and luminal content it remains uncertain if the ozone dose is effectively utilized.
  • BOEX has distinct advantages; it is simple to perform, fairly inexpensive, non-invasive and does not involve handling of potentially infectious blood. There have noted some problems: the cabin must be well insulated and BOEX is best performed in rooms that have an entrance room, treatment room and another room with a shower. Whether this approach will truly become useful remains to be established by random clinical trials, but at this stage it seems to represent a promising tool to modify the biological responses in some pathological states:
  • The activation of the immune system may be useful in chronic viral diseases (HBV, HCV, Herpes1 and 2, HIV HPV). It may be proficient to treat chronic fatigue syndrome even though it is probably not a viral disease.
  • Metastatic cancer, to avoid palliative chemotherapy, which is usually useless and associated with negative prognosis. However, it could be even tried as an immunoadjuvant at earlier stages with polychemotherapy. Cancer is a progressive disease and without deceiving the patient it may be possible to improve the quality of life.
  • Vasculopathies, particularly hind limb ischaemia due to atherosclerosis, Bueger disease and diabetes. Necrotic ulcers and dystrophic lesions must be stimulaneously treated with topical therapy. Patients with severe coronary atherosclerosis, recent myocardial infarction or severe hypertension may undergo BOEX BUT without hyperthermia, starting with a 10 minute period and scaling up slowly. Patients with asthma and BPCO must also be treated cautiously. However it can be added that vasculopathies are positively sensitive to ozonetherapy.
  • Age related macular degeneration, exclusively the atrophic form. Keeping the heat at a low level.
  • Sclerodermia with Raynaud’s phenomenon.
  • Moderate burns, to prevent or reduce bacterial infections and enhance healing.
  • Some muscular-tendinous lesions in athletes, to reduce muscle contraction and alleviate pain.
  • Skin disease such as infections, psoriasis, perhaps atopic dermatitis and eczema.
  • Advanced lipodystrophies, such as Madelund disease. The Lipodystrophy occurring during highly active anti-retroviral therapy may also be advantageously treated. However, no claims can be made to cure HIV-AIDS

Our provisional protocol envisages a course of 2 – 3 treatments weekly during the first and second weeks but it must be taken into account the patients age, stage and type of disease. We always insist on the “start low, go slow” paradigm to allow for the adaptation to Chronic Oxidative Stress. The heating should be gradually scaled up from 30 degrees to no more than 42 degrees with periods from 10 minutes to a maximum of 30 minutes. Normal subjects interested in using Ozone Steam Sauna Therapy as an anti-aging approach may afford to do 5 treatments weekly spending 30 – 35 minutes in the cabinet.

Contraindications for Ozone Therapy

  • People with a significant deficit in G-6PD (An enzyme that helps red blood cells function normally). Favism is a haemolytic disease observed in some people lacking the enzyme
  • Patients being treated with Angiotensin-converting Enzymes (Used to treat high blood pressure, Heart Failure, Diabetic Nephropathy, Type 2 Diabetes)
  • Abnormal situations with hyperthyroidism, thrombocytopenia and serious cardio vascular instability
  • Allergy to ozone has been claimed, but what is it? I rekon that the hypersensitivity of asthmatic patients breathing air polluted with ozone has created some confusion. Moreover the use of plastic bags may induce the release of an allergic component from the plastifying material. The undoubtful strong reactivity of ozone and its toxicity for the respiratory system during prolonged exposure to polluted air have contributed to establish the dogma that ozone is always toxic. This is incorrect.

Ozone will dissolve in the water of the lungs, but there are no protective antioxidants to neutralize the ozone like there is in the skin. This causes irritation and leads to the lungs releasing huge amounts of toxic components which are able to enter the circulation and cause multiple organ damage. The more pollution, the more there is toxic ozone around, but people are not allergic to Ozone in its pure form.