Beyond the Influencer Hype: Extracorporeal Blood Oxygenation (EBOO or EBO2), Major Autohemotherapy, Hyperbaric 10 pass Ozone therapy and other blood ozone therapies for Longevity – Risks and Realities

All of these procedures, which involve oxygenating and sometimes filtering blood outside the body, are trending with biohackers and longevity influencers. There are some small nuances between them in terms of concentration of ozone used and whether a filter is involved. Extracorporeal blood oxygenation is a critical procedure for many patients with severe respiratory or cardiac illness, and can be life saving in these cases. I've also been aware of ozone therapy for enhanced healing of diabetic ulcers and peripheral artery disease for some time, but now people are claiming it can slow aging,"detoxify"or "boost energy levels" (my favorite vague wellness claims). Let's dive into the potential risks and benefits.

These therapies involve just a few steps:

• IV Blood withdrawal

• Oxygenation/Ozonation: The blood is passed through a machine that adds oxygen O2 or ozone (O3, a highly reactive form of oxygen), or ozone is infused into a bag of blood

• Filtration: The blood may be filtered to remove certain molecules or proteins. Major autohemotherapy and 10 pass ozone therapy do not involve a filtration step.

• Return of oxygenated/ozonated blood - The treated blood is then returned to the body.

  
  

Potential Risks of EBOO for Wellness:

While EBOO is marketed as a longevity enhancer, it's essential to understand the potential risks:

• #1 Lack of Scientific Evidence: The majority of studies that show clinical benefit outside of an ICU setting are studies on rheumatoid arthritis, wound healing, diabetic ulcers and peripheral artery disease. Some of these studies suggest ozone therapy as an effective complementary therapy. There is also some literature that suggests a mechanism of increased antioxidant production, such as this study Mild ozonisation activates antioxidant cell response by the Keap1/Nrf2 dependent pathway https://pubmed.ncbi.nlm.nih.gov/29864481/ .

  However the clinical impact of ozone use in healthy patients is unclear.

  
  

  An overall lack of clinical research also means that there are no clear protocols on optimal dosing for this procedure when used for general wellness/longevity. For example, one clinic I found discusses therapies ranging from "3000ug of ozone to treat about 200 ml of blood. Hyperbaric Ozone uses about 14,000ug of ozone to treat 200 ml of blood, and this is done 10 times...140,000ug of ozone...to treat about 2000ml of blood. The HiDose O3 method uses around 70,000ug of ozone to treat 200-300ml of blood in a single pass."

These doses being used in clinics can be 7 to 70x what researchers of low dose ozone therapy consider an "ideal concentration range of 20–30, maximum 40 µg/mL and at a dose of 1000–1500 µg, maximum 2000 µg per MAH treatment."

(https://pmc.ncbi.nlm.nih.gov/articles/PMC8346137/#sec4-ijms-22-07890)

Besides this extreme variation in dosing, there is no clear data on the durability of this therapy or recommended frequency for this therapy. It is not reasonable to extrapolate the frequencies of administration from studies such as those on rheumatoid arthritis (in which some patients were treated daily, weekly and every 2 weeks), to healthy patients.

Without good evidence, providers have an incentive to tell patients to get the therapy more frequently than may be necessary, without any idea of the short or long term implications for a healthy person.

• Adverse Reactions to Ozone: O3 is highly reactive which means that, especially at high doses, it can damage cells and tissues by oxidizing lipids, proteins and DNA. However, like all things, the poison is in the dose, and there may be a overall beneficial hormetic effect exerted by ozone at low doses.

  
  

  Some studies do suggest compensatory stimulation of antioxidant production (like superoxide dismutase and glutathione peroxidase) by cells due to oxidative stress. This may paradoxically explain some of its benefits for diseases like peripheral artery disease, etc.

  
  

  This is analogous to what we observe with exercise. Exercise induces a small amount of oxidative stress, resulting in increased production of antioxidants like superoxide dismutase and glutathione peroxidase.

• Cost $200-600/session

  
  

• Damage to blood cells: The process of running blood through a machine can cause damage to blood cells. Ozone can also cause red blood cells to rupture, which is another reason dose is essential, and over dosing is a terrible idea.

Some less likely but still serious possible risks

• Reaction to materials: A patient may have a reaction to the materials used in the tubing, or the machine itself.

• Infection: This risk should be minimized by a hygienic facility. Any procedure involving blood withdrawal carries a risk of infection at the insertion site or within the bloodstream.

• Blood Clots: Changes in blood flow and contact with foreign surfaces can increase the risk of blood clots.

• Air Embolism: Highly unlikely. If air enters the bloodstream, it can cause a potentially life-threatening air embolism.

• Electrolyte Imbalances: Minor and easily treated possible side effect for healthy patients with functional kidneys.

  
  

Potential Benefits:

Proponents of EBOO for wellness will often claim:

• Increased Oxygenation: The procedure does increase blood oxygen levels temporarily. It has not been suggested by research that this leads to any sort of clinically meaningful outcome.

• Detoxification: Some claim EBOO removes toxins from the blood.

  • One practice I've seen claims that during EBOO a "specialized BPA- and DEHP-free dialysis filter is used to remove lipids, cholesterol, heavy metals, petroleum products, free radicals, toxins (bound to beta-2 microglobulin), and inflammatory proteins from the body, making it highly effective at halting the inflammatory cycle. As blood passes through the filter, it is brought into contact with ozone which optimizes the filtration process, stimulates the NrF2 detoxification pathway, increases nitric oxide, and accelerates mitochondria via increasing NAD+ and ATP. Lastly, the “clean” blood is passed through a device which uses UVA, UVC, red, green, amber, and blue lights to further impede viruses and bacteria, energize mitochondria, and activate NAD+."

    
    

    Wow! Sounds like people are going to have some VERY energized mitochondria!

    
    

    The Nrf2 pathway basically just increases antioxidants in response to oxidative stress (superoxide dismutase and glutathione peroxidase), like I discussed above. This could be beneficial, but there's nothing extraordinary happening in terms of detoxification here.

    
    

    Vague claims like these about NAD+ activation and super powered mitochondria are just ridiculous. Yes, the mitochondria use oxygen to make ATP. But there's nothing magical about ozone (O3). If anything, the direct effect of ozone would be detrimental to mitochondrial function, given how oxidizing it is relative to regular oxygen. There may again, however be a benefit to mitochondria through the hormetic effects of increased antioxidant production that can be provided by low doses of ozone.

    
    

    There is not also enough research on ozone (O3) to understand what dose may possible boost NAD+ through hormesis, however there is very clear evidence that too much ozone can deplete NAD+.

    
    

    (You can read all I have to say about NAD+ Here.)

  
  

• Most medical research suggests the human body's natural detoxification systems (liver and kidneys) and immune system work perfectly adequately at performing these functions. (I'm going to have to write a post on general claims about detoxification soon since this is one of the most abused buzzword claims in wellness)

  
  

• Enhanced Immunity: There are no high quality studies that support this claim. It is plausible that immune cells could experience a period of better function through increased oxygenation of the blood, but investigation of this hypothesis and whether it is a clinically significant effect needs more research. Ozone can disinfect water and medical equipment but that doesn't mean putting it into blood, at doses that would not seriously harm humans, will kill viruses and bacteria. Some clinics claim that O3 dissociates into peroxide in the bloodstream, killing pathogens, but again there are no studies demonstrating this effect.

  
  

  Some clinics correctly note that ozone therapy helping with autoimmune conditions, and there are some studies that suggest ozone in combination with methotrexate may reduce pain for patients with rheumatic arthritis.

  
  

• Increased Energy: Some people report having more energy. That's great anecdotally, but not great science.

  
  

The Bottom Line:

If you are a healthy patient, don't waste your money on an elective therapy for which the most evidenced benefit (a hormetic increase in endogenous antioxidant production via mild oxidative stress) can also be achieved through exercise, without the costs, risk and uncertainty of dosing.

Just exercise instead.

Extracorporeal Blood Oxygenation (EBOO/EBO2) use for longevity does not have sufficient scientific evidence to claim clinical benefit in healthy patients and carries potential risks. There is limited evidence of improved microvascular health and improved wound healing, albeit in patients who already have peripheral artery disease or diabetes. You should be aware of the potential complications associated with EBOO discussed above.

My big general takeaway lesson here is to be wary of unsubstantiated, but impressive and scientific sounding claims.

If a health care professional makes a claim about a procedure or treatment that sounds compelling (Gives you energy! Boosts mitochondria, NAD+, immunity! Detoxfies you!), ask for the data. What kind of studies have been done in humans? How long did the studies last and what doses were used? What were the indications? What outcomes did they measure and how? If there is not a clearly measured outcome in humans, what other data exists to support the claim? Animal studies? In vitro studies? A few in vitro studies showing a potential mechanism are generally not sufficient, and can easily be manipulated to sound scientific. Don't rely on anecdotal evidence or marketing hype.

Always remember, longevity and healthspan optimization are a decades long project. Before trying out an expensive procedure with potential risks, carefully consider the level of scientific evidence available.