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What is the difference between hyperbaric oxygen and ozone therapy?


Hyperbaric Oxygen Therapy (HBOT) involves breathing in pure oxygen under increased pressure in a special pressurised chambers. This form of therapy is available on the NHS for specific medical condition, e.g for radiotherapy side effects. It has also been promoted as a complementary therapy e.g for chronic fatigue and post-viral illnesses. 


Most oxygen carried in the blood is bound to haemoglobin with only a small percentage of oxygen dissolved in the plasma (the liquid part of the blood). It is this proportion of oxygen that can be increased if oxygen is inhaled at high pressure. Breathing oxygen at high pressure thus increases the blood oxygen-carrying capacity by allowing the plasma to carry more oxygen. The proportion carried in plasma can be sufficient on its own to support tissues without a contribution from haemoglobin. As the oxygen is in solution, it can reach physically obstructed areas where red blood cells cannot pass. This enables tissue oxygenation even with impaired haemoglobin oxygen carriage, such as in carbon monoxide poisoning and severe anaemia. This can create an environment that is more conducive to healing such as in trauma, severe infections, radiotherapy damage to blood vessels and skin grafts.  


Extra oxygen in the blood however causes vasoconstriction (narrowing of blood easels) but this is more than compensated for by increased plasma oxygen carriage with the net result in favour of more tissue oxygenation. Such vasoconstriction does however reduce tissue swelling, a desirable effect in crush injuries and burns.


HBOT also has an effect on fighting infections, particularly those caused by bacteria that prefers low-oxygen environments (anaerobic bacteria). Oxygen also facilitates an oxygen-dependent defence system by which the white cells kill bacteria. 


In summary, HBOT has complex effects on immunity, oxygen transport and haemodynamics. The positive therapeutic effects come from a reduction in hypoxia and oedema, enabling normal host responses to infection and ischaemia.


From the above description you can see some similarities between ozone therapy and HBOT, in particular the improvement in tissue oxygenation and the effect on the immune system. However there are some important differences in the underlying mechanisms of action. For example: HBOT improves tissue oxygenation by directly providing more oxygen to the tissues from breathing 100% oxygen at high pressure. This effect does not persist long after the end of of the session, a reason why HBOT usually needs prolonged daily or even twice daily sessions. This is because oxygen is rapidly utilised by the body once the external source of oxygen is interrupted. Ozone therapy on the other hand improves delivery of oxygen to the tissue by a completely different mechanism: ozone increases the level of a specific enzyme in red blood cells called 2,3-diphosphoglycerate (2,3-DPG) which helps the red cells to offload more oxygen to tissues. The levels of 2,3-DPG do not fall immediately following cessation of the ozone session thus allowing a prolonged and a more natural increase in tissue oxygenation. 

Secondly, the effect on the immune system is more complex with ozone therapy with signalising cascades put in motion creating a whole host of effects on the immune cells, including inducing the cytokines system. Ozone also has a direct toxic effect on micro-organisms. 


It is also important to remember that ozone therapy involves giving at least 95% oxygen in addition to ozone. The oxygen simply works as a career to deliver ozone to interact with the blood, or when locally applied such as in the treatment of ulcers, oxygen and ozone work together to improve tissue oxygenation (both) and sterilising the ulcer (ozone only). 


In summary: Ozone and HBOT share some similarities with ozone having more modes of action and more sustained effect. Ozone is also delivered as a mixture with oxygen but most of the beneficial actions are mediated by the ozone.  

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The "10 passes" and "EBOO" vs low ozone concept; which is better?

There are 2 ways to deliver ozone into the body:


1- The Extracorporeal (outside the body) method: This entails extracting blood and mixing it with ozone outside the body. In this category, there are 3 main techniques: a) the Major Autohaemotherapy (AHT): this is the preferred European technology using vacuum bottles; b) the multi-passes system: Repeated (up to 10) volumes (also called passes) are extracted and mixed with ozone before returning each pass back to the body; c) EBOO (Extracorporeal Blood Oxygenation and Ozonation which is similar to performing haemodialysis and adding ozone to the blood as it passes through the machine in low steady concentrations.   


2- The Intracorporeal (inside the body) method: This entails injecting the ozone directly in the veins where it circulates and mixes with the blood inside the body. There are 2 ways to do this: a) Direct gas injection: This is dangerous and prohibited by all ozone scientific societies around the world; b) Ozonated Saline: This is the Russian traditional method (see next QA) and the only method of safe intracorporeal administration. It is done by continuously passing ozone gas through the infusion solution and administering the mixture. 

Despite the publicity of the EBOO and the 10-passes, the fact remains that these methods are not endorsed by the reputable ozone societies in the countries that pioneered ozone therapy e.g European countries (including the German Ozone Society) or Russia. These scientific societies advocate a different approach where the volume of blood and the dose of ozone has to be carefully calculated based on body weight and the body's tolerance to ozone in order to give the maximum benefit without toxicity. The practice of high doses ozone is however prevalent in some private clinics in countries where ozone therapy practice is not regulated eg UK and USA.

It is claimed that the 10 passes or EBOO give better results because of the higher volume of blood ozonated. It is also claimed that the 10 passes ozonate 10 times the blood volume in comparison with the Major AHT, which could amount to 2 litres (about half of the blood volume in an adult). This conclusion is based on this simple calculation: 200 ml per pass x 10 times = 2 L.

The above argument may seem logical but it is scientifically incorrect. Firstly: The blood inside the body is not stationary, the heart pumps the whole blood volume every 1 minutes. This means that when the ozonated "pass" is injected back into the body, it mixes with the rest of the non-ozonated blood so when the next "pass" is extracted for ozonation, some of already ozonated blood will also be extracted again. Professor Dr Eugeny Nazarov, a Russian Ozone expert, calculated that to ozonate 95% of the blood using the multi-pass technique, we need to perform  97 passes, 150 ml each. You can watch this conference lecture by clicking on this link (discussion of this point starts on the 25th minute into the presentation). Secondly: The amount of anticoagulant needed for the 10 passes is 10 times the amount needed for Major AHT thus significantly increasing the risk of internal bleeding especially in the hours immediately following therapy. 


Furthermore, it is technically possible to administer high concentration of ozone using ANY method by simply increasing the concentration and / or the volume of blood mixed with blood without having to repeatedly extract new volumes. As explained in the mechanism of action of ozone, ozone does not act directly. Once exposed to the blood, zone interacts within 1 second with the components of the blood to produce secondary messengers that perform the desired actions. When the ozonated blood is returned back to the body, these secondary messengers mix with the whole volume of blood inside the body so there is no need for the ozone gas to come in contact with all of the blood to get the desired effect. 

High concentration ozone therapy was the norm 20 years ago until replaced (at least in Europe) by the modern “low ozone concept” with high concentrations reserved for treating external infections such as infected ulcers. You can have more information about the low ozone concept from the German Ozone societyWhile it is true that ozone in high concentrations is directly toxic to micro-organisms but it is also equally true that ozone in such high concentrations is also toxic to the human cells. The figure below (from the German Ozone Society Handbook, 2020) depicts the above argument by providing the changes in the level of some of the antioxidants triggered by ozone therapy at various concentrations. You will see that the therapeutic effect is obtained between 10 and 40 mcg/ml with a "sweet spot" around 30 mcg/ml. Other European guideline are in agreement with this. At LOC we employ ozone doses within this range, starting from the bottom of the therapeutic range (10 mcg/ml)aiming to reach 30 mcg/ml gradually depending on the person's tolerance and medical conditions. We use either Major AHT or the Russian method of ozonated saline to achieve this. 

So in summary: ozone is a drug, higher dose does not necessarily mean better response. The dose and the volume of blood have been established beyond doubt by research. The latest advances in our understanding of ozone therapy on the cellular level enabled a shift in the ozone therapy practices towards the low ozone concept.


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More about the 10 passes/EBOO

Q- Why don't people die or get serious side effects from excessive ozone exposure during the 10 passes?

Considering the earlier discussion, one might anticipate severe side effects, even potential fatalities, when undergoing 10 passes involving high ozone doses. However, such incidents are rare, owing to the specific method employed during the 10 passes. The technique of Major Autohaemotherapy (MAH) should be performed according to the standards set by the International Scientific Committee of Ozone Therapy, accessible from this link. MAH is considered equivalent to a single pass for the purpose of this discussion. These standards advise "adjusting the flow speed to approximately one drop per second. The entire procedure may take 20 to 30 minutes and should NEVER be rushed." In other words, a single pass (MAH in this case) should take 20 to 30 minutes. If 10 passes are performed consecutively, the procedure should take 200 to 300 minutes (approximately 3.5 to 5 hours). However, in reality, automated machines complete the 10 passes in about an hour. These machines limit the time for mixing ozone with blood to a few seconds and then return the blood to the patient under pressure, which contradicts the recommendations of ozone therapy authorities who advise against pressurized blood re-infusion during MAH "to avoid unnecessary risks". It has been conclusively demonstrated that if ozone gas is mixed with blood hastily to shorten the procedure's duration, most of the ozone remains in the mixing container and does not interact with the blood. Dr. Bocci, a renowned Italian professor with an interest in ozone therapy, has documented his experiments in his book "Ozone: A New Medical Drug." In this book, he argues that the MAH procedure should take 40 minutes, with blood mixing done manually and gently over 5 minutes to ensure thorough ozone-blood interaction.


In light of the above discussion, it can be concluded that the 10 passes (and the 20 or 30 passes currently promoted by some clinics) would indeed deliver a toxic or potentially lethal ozone dose if performed correctly. However, because it is rushed, the patient is highly unlikely to receive the intended ozone dose they paid for, which ironically can be seen as a positive outcome. The total dose delivered in a multi-pass system can be achieved in a single pass without the added expenses and risks associated with high anticoagulant doses for each pass. The spectacle of blood moving up and down 10 times or more may be visually appealing but is scientifically incorrect and risky.

Q- OK, what about the assertion of "stem cell activation" mentioned on websites advocating for the use of multi-passes?

Many of these clinic websites promote the 10 passes as a superior method for administering ozone therapy, claiming that high ozone doses "activate the bone marrow" to release stem cells into the bloodstream, which, according to these clinics, aids in the "healing" process. To examine this assertion, we should begin with a fundamental understanding of physiology: Blood cells are generated in the bone marrow from stem cells. These cell lines progress into mature cells before being released into the bloodstream. Having an abundance of immature cells or even stem cells in the bloodstream is not indicative of good health. The body releases these cells prematurely when there is severe blood loss or destruction in an attempt to "fill the gap" and maintain circulation. This phenomenon is well-recognized in medicine, for example, in cases of sudden hemolysis (the breakdown of red blood cells) or significant bleeding. In such situations, the bloodstream will be filled with immature forms of blood cells, detectable under microscopic examination. These cells do not migrate to other organs and initiate a "healing process." Instead, they are simply undeveloped cells mobilized to replace those that have been destroyed as a consequence of excessive ozone exposure. Another situation where plenty of immature cells and stem cells are found in the blood stream in abundance is in blood cancers such as leukaemia, however this is unrelated to our discussion. 


In summary, the assertion that high doses of ozone "stimulate" stem cells is a misrepresentation of scientific facts. Stem cell therapy is completely different. The immature cells that may be observed following the 10 passes are indications that the body has suffered a substantial destruction of blood cells due to interaction with high doses of ozone. As a coping mechanism to maintain blood volume and oxygen delivery, the body releases immature cells into the bloodstream.

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Is ozonated saline any good?

Ozonated saline is rarely practiced outside Russia. Despite this it is probably the most researched method of ozone therapy. The following is an extract from the International Scientific Committee of Ozone Therapy (Madrid Declaration on Ozone Therapy; 3rd edition;

This is a testimony from the European ozone experts that is hard to ignore. At LOC we are pleased to announce that we offer this method to our patients, especially for people with thin veins or who prefer a less invasive way of ozone therapy.



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Can vitamin c and ozone be given together?

The question of whether it's appropriate to simultaneously administer high-dose vitamin C and ozone therapy is a common one. A cursory internet search suggests that this combination might not be advisable. This perception is rooted in the simplistic notion held by some that vitamin C is an "antioxidant," while ozone is a "pro-oxidant," leading to the belief that they counteract each other. Some laboratory research on blood products has been conducted to support this viewpoint. However, like most matters, a deeper understanding of the intricacies can shed light on the possibility and even desirability of employing both potent therapies together.


It's crucial to note, before delving further into this discussion, that there are NO human studies supporting the idea that vitamin C and ozone neutralize each other when administered concurrently through standard methods. The following discussion is, therefore, grounded in a comprehensive comprehension of the mechanisms underlying each therapy, with an aim to form an opinion on their co-administration.


Certainly, ozone is an oxidant, and vitamin C is an antioxidant, which logically suggests they may cancel each other out when administered simultaneously. Nevertheless, vitamin C, when administered in higher doses (e.g. over 25 grams intravenously), undergoes a shift from its antioxidant role to acting as a pro-oxidant. By applying this logic, it becomes plausible to combine high-dose vitamin C with ozone because they are now functioning in a synergistic manner. It's essential to clarify that this is not a recommendation, but rather a demonstration that this approach could be considered feasible or even desirable.


In reality, ozone undergoes a transformation when it interacts with the bloodstream or tissues. Studies have confirmed that ozone promptly interacts with blood cells upon entering the circulatory system during major autohemotherapy. In simpler terms, ozone vanishes from circulation within a few minutes of administration, leaving behind only the byproducts of this interaction, collectively referred to as "ozonides," which produce the beneficial effects associated with ozone. This crucial point is strongly emphasized in the latest guidelines from the German Ozone Society, as illustrated in the provided screenshot:



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Unlike ozone, high-dose vitamin C remains present in the bloodstream for extended periods following infusion, with the duration dependent on the dosage. The following extract from the Riordan Clinic High Dose Vitamin C Protocol highlight this fact:



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Drawing from the earlier explanation, it is possible to combine ozone and vitamin C in a single therapy session, but ozone should be administered initially, followed by vitamin C, with a brief interval in between. This interval, which might only require a few minutes, ensures complete utilization of ozone before commencing with vitamin C. Research has indicated that this approach yields more favorable results when compared to administering these therapies individually, especially within the context of cancer treatment. Click this link to access the original article from The Journal of Ozone Therapy confirming that the researchers used "simultaneous high dose of Vitamin C [and] Major Auto Haemo Therapy (MAHT) for more than hundreds of cases with much better results". The authors of another paper (check this link) recommend the administration of both therapies for better effect in the context of cancer therapy using the above mentioned sequence with a generous gap of 30 minutes. This is the important extract from this paper:





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At Leicester Ozone Clinic, we firmly advocate for the simultaneous administration of vitamin C and ozone therapy. Our preferred procedure involves the administration of ozone initially, followed by vitamin C. We conducted bedside blood tests at the conclusion of the infusion on many occasions and we are satisfied that high levels of vitamin c are achieved after ozone therapy. Also, remarkable clinical outcomes have been consistently observed with this combined approach. Additionally, the use of the ozonated saline method, also known as the Russian method, is particularly suitable due to its requirement for a minimal amount of ozone infused over longer periods of time, which minimizes the likelihood of interaction with vitamin C or other antioxidants.





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