Comparing Intravenous (IV) Ozone Therapies

IV ozone therapy is the administration of medical grade ozone gas into the blood.  A medical practitioner draws some blood (usually a small amount), diffuses it with ozone, then infuses it back into the vein. 

What is IV ozone therapy used for?

IV ozone treatments are typically used for chronic disease and infections — Lyme, mold toxicity, cancer, diabetes, autoimmune disorders, and more.  There are also many professional athletes, amateur athletes, and biohackers who use ozone therapy for performance enhancement, since it improves blood flow and oxygenation.

Some uses for intravenous ozone treatments include:

• Lyme disease
• Mold toxicity and mycotoxin illness
• Autoimmune diseases (rheumatoid arthritis, celiac, Hashimoto’s, Graves’, multiple sclerosis, etc.)
• Cancer, especially for patients undergoing chemotherapy
• Interstitial cystitis
• Biohacking and performance enhancement
• Herpes infections
• Fungal, viral, and bacterial infections
• Respiratory infections
• Liver diseases and hepatitis
• Ischemic and lack of oxygen diseases

Ozone therapy is a strong antiviral, antibacterial, and antifungal treatment.  In addition, it puts the body in a better state to fight disease by improving oxygenation, blood flow, and balancing the immune system. That’s why ozone therapy is used for such a wide variety of ailments. 

Check out this article for a deep dive into how ozone therapy works.

What are the benefits of IV ozone treatments?

Patients will generally feel the following after a number of IV ozone treatments:

• Increased energy and alertness
• Reduced brain fog and increased clarity/cognition
• Reduced negative side effects from conventional treatments like chemo
• Improved stamina and ability to maintain higher levels of energy during exercise
• Reduced bloating and gut discomfort
• Reduced pain and inflammation
• Overall improved quality of life in patients with chronic disease

What are the risks of IV ozone therapy?

Ozone therapy has a low rate of adverse events, making it relatively low-risk in comparison to most medical procedures.  The most common negative side effect (though still only affecting a small percentage of patients) is a Herxheimer reaction, which can sometimes result in flu-like symptoms in patients with a burdened or underperforming immune system. 

A Herxheimer reaction occurs when medical grade ozone wakes up that sleepy immune system. The immune system starts attacking infection quickly which releases toxins from the dead germs. All those dead germs start piling up faster than the body can get rid of them, which is what causes the sick feeling that can last from a single day to a full week. 

However, a Herxheimer reaction can be avoided with proper care from a doctor.  Typically this involves a detoxification protocol and starting off at a really low dose of IV ozone therapy.  Then, after the first IV ozone treatment is administered, they look for signs of a Herxheimer reaction.  Based on the patient’s response, they may increase or decrease the dose the next time an IV ozone treatment is done. 

I’ll explain more about doses later in this article, but the goal is to start low and slow to allow the immune system to slowly eliminate a present chronic infection.  Of course, this slow increase of IV ozone is typically only necessary in people who are highly sensitive, present many allergies, or have a chronic infection.  

Is IV ozone therapy safe?

Most people know breathing ozone is a bad thing even if they don't know why. Ozone will interact directly with the lung tissue, causing oxidation.  Oxidation in the lungs is bad news because they don’t have any antioxidant defenses. 

However, ozone can safely be applied to other parts of the body such as the blood, vagina, or rectum.  The antioxidants present in those areas quench the ozone, which causes a cascade of beneficial effects.  

The International Scientific Committee of Ozone Therapy (ISCO3) published a survey in “Ozone Therapy and Its Scientific Foundation” showing that ozone therapy has a higher safety record than aspirin.  

For every 100,000 IV ozone treatments given, there were 6 adverse events.  And those were primarily due to the use of heparin or misuse by the practitioner.

This is an adverse event rate of 0.00006%.

Is IV ozone therapy FDA approved?

IV ozone therapy is commonly used in integrative, natural, and alternative clinics because it has not yet been approved by the FDA.  An FDA approved ozone therapy machine is not currently available.  

Under a company called Vasogen, ozone therapy made it through rounds one and two of the FDA clinical trials for efficacy and safety.  But due to a poor financial model, Vasogen folded without producing a fully FDA approved ozone therapy machine.

It is not illegal for doctors to administer ozone therapy under a code that allows them to take and modify the usage of a device.  There are certain state boards that allow for the use of ozone therapy in clinics.  Practitioners are accountable to their medical boards, which vary from state to state and based on licensure, not the FDA.  

Typically a practitioner is going outside of standard of practice to administer IV ozone therapy, as most natural or integrative practitioners do.  

But with a strong informed consent, relationship, and education of the patient, a practitioner can typically mitigate most of the legal risks associated with intravenous ozone therapy treatments.  By virtue of practicing medicine and helping people heal, a doctor assumes risk for many of the treatments they administer.  

Why are there multiple protocols and administration methods for IV ozone therapy?

Ozone therapy started in Europe in the early 20th century and quickly migrated to other countries due to its effectiveness in treating infections during war.  Then, it started to spread into Asia before finally reaching North and South America.  Each country started to develop their own methods of ozone therapy based on what they had available and expertise of the doctors.

When ozone therapy started to become more unified in the scientific realm through technology advancements in the period from the 1960’s to the 1990’s, many countries and experts brought their own methodology to the table.  

There are also different lines of thought on the best way to administer ozone therapy.  Some doctors prefer using different volumes of blood or concentrations of ozone.  But all methods listed below seem to have a beneficial effect because research indicates that ozone therapy has a large window of how much ozone can be applied.

What are the differences between IV ozone protocols?

The primary difference between the protocols comes down to two things:

1. How much ozone is administered 
2. How much blood is used in the process

For most IV ozone therapies, there are not good comparative studies to show which one is best in a certain situation.  Doctors may choose a certain protocol based on their experience with which method works best for a given purpose.

Standard major autohemotherapy IV ozone is the most clinically and scientifically verified method of IV ozone. This method is adopted by about 80–90% of medical practitioners using ozone therapy.

How do you calculate a dose of ozone?

A dose of ozone has two factors.  

1. The strength of the ozone gas, called gamma or ug/ml — micrograms per milliliter
2. The volume: how much gas is present.  Volume is typically measured in mL (milliliters) or CC (cubic centimeters), which are the same thing

You can find more information on calculating a dose of ozone for ozone therapy here.

Low dose IV ozone vs. high dose IV ozone

The International Scientific Committee of Ozone Therapy (ISCO3) is the most credible ozone therapy organization to date, and does a fantastic job with detailed instruction and information. But there’s a wide range of practical knowledge and experience among practitioners regarding doses. Since I’m writing for an audience that is learning about ozone, I am using definitions that are slightly outside of what you would find from organizations like ISCO3. If I were to cover every nuance, I’d need a much bigger website. 

According to researchers such as Dr. Lamberto Re, the guidelines set forward by the ozone therapy organizations intentionally use large dosing windows (how much ozone can be used in a treatment).  For example, writing a guideline of 10 to 60 gamma rather than giving a strict rule of 40 gamma.  

This way, doctors can make judgements based on their clinical experience.  ISCO3 does note that the maximum dose of ozone therapy that can be safely applied is under 80 ug/ml with a gas to blood ratio of 1:1.

With all this in mind, I am defining a low dose treatment of IV ozone as:

• 10–60 ug/ml concentration
• Ratio of gas to blood of 1:1 or less gas volume (ex. 1:2 gas to blood)
• No more than 300cc of blood drawn 

The higher half of this range would not actually be considered a low dose treatment by ISCO3, but for simplicity I’m grouping together low and middle doses.  

I am defining a high dose treatment of IV ozone as anything that exceeds the above. For instance:

• 50–80 ug/ml concentration
• Ratio of gas exceeds a 1:1 ratio with blood (ex. 3:2 gas to blood) 
• OR more than 300cc of blood is drawn

The dosing range everyone agrees on

There are some clear parameters when it comes to IV administration of ozone gas.  Ozone will begin to oxidize red blood cells, white blood cells, and other important cells in the blood when the concentration of ozone exceeds 80 ug/ml per ml of blood. 

So you never see an IV concentration over 70 ug/ml applied per ml of blood.  

Doses in other forms of administration, such as rectal, vaginal, skin, ears, etc. have different dosing recommendations.  For example, rectal insufflation is not to exceed 40 ug/ml while skin applications can tolerate concentrations around 110 ug/ml.

Common dosing ranges of the most common therapies

Above you can see the dosing ranges for the most common IV ozone protocols.  

Is more ozone better?

If something works at a low dose, it would seem to make sense that a higher dose would be even more beneficial. This faulty reasoning makes some people gravitate towards higher doses and stronger treatments without even realizing it. 

Breaking down the low dose concept

Ozone scientist Dr. Renate Viebahn-Haensler published a paper that explains how ozone therapy is a hormetic therapy and the best therapeutic responses are found in lower doses of administration.

However, the entire premise of the paper is contained in this section —

“Data on the toxicity of ozone (mitotic index, cell aberrations, chromatic breaks) determined in (intraperitoneal) animal studies using mice show cytotoxicity at 2300 µg/kg, and a slight clastogenic activity at 1400 µg/kg mouse at 70 µg/ml. When administered intraperitoneally on 15 subsequent days, low concentrations of 4, 11, 20, and 35 µg O3/ml, showed no toxicity, even at volumes of 80 ml/mouse (approx. 30 g body weight) (Fernández et al. 1989). This means that whether ozone is therapeutically useful or toxic is determined by both concentration and dose.

Compared with this, in humans, the doses of 21.4 µg ozone/kg body weight applied (70 kg) in major autohemotherapy and 107 µg ozone/kg body weight in rectal insufflation are low, and can be administered over an extended period of time without any adverse effects. To make full use of the bioregulative function of ozone, low concentrations and small doses are required in the standardized applications (Figure 12). Figure 13 gives a concentration/effect relationship for systemic ozone applications.

In layman’s terms, they performed intraperitoneal injections on mice and applied that information to forms of IV ozone on humans.  While the intraperitoneal injections and weight correlations are interesting, they do not provide a sufficient argument to say that higher doses of ozone are not as effective as lower dosages.

That being said, a lower dose of ozone therapy (defined as 10–60 ug/ml and a 1:1 volume of ozone/oxygen gas to blood with less than 300mL of blood drawn) is by FAR the most scientifically proven method of ozone administration.  

It has the most literature, most documented outcomes, and the most doctors using it worldwide.  It is also the easiest to apply and the least expensive option. 

Thoughts on high dose administration

There is no definitive evidence showing that higher doses of ozone therapy are better than lower doses.  Some data can be found showing the benefits of EBOO and 10 Pass, especially in case reports.  But this data typically does not compare with MaH or lower doses of ozone therapy.  So no good comparison data is readily available.

Clinical experts in EBOO, 10 Pass, and HiDose may have clinical experiences that lead them to say a higher dose of ozone therapy is more effective.  This is difficult to make an opinion on because it’s information they retain in their head from patient outcomes and usually don’t have tangible data to show.  

If you are a practitioner, it’s best to start with a standard Major Autohemotherapy form of administration.  As you gain clinical experience, you can work with other methods and make evaluations on the effectiveness for yourself.

Some risks are heightened with high dose administration

• Patients with a G6PD deficiency or deficiency in antioxidant enzymes
• Hemolysis of the blood
• More potential for blood contamination from materials exposed to ozone
• A highly burdened immune system could trigger a strong Herxheimer reaction

How to select the best IV ozone for your clinic

Any form of IV ozone administration is better than nothing.

Usually, it’s best to start with MaH (major autohemotherapy) for these reasons:

• Lowest cost to get started
• Easiest to administer
• Most proven method for effectiveness
• Used for chronic disease and optimization

After you gain experience you can look into higher doses.

How to implement IV ozone therapy into your clinic

Here are the steps to starting ozone therapy into your clinic:

1. Get trained
2. Get Equipment
3. Utilize our resources to continue to grow

How many sessions of ozone therapy are necessary?

There are several factors that determine the amount and frequency of sessions:

• Which form of IV ozone therapy is being used
•  The experience of the practitioner
•  The patient's reason for treatment
•  The patient’s financial situation
•  How much time the patient has available.

Every form of IV ozone therapy is a little different, but here are some general guidelines for Major Autohemotherapy (the most common IV ozone treatment). 

• Some benefit: 2–4 IV ozone treatments over 1–4 weeks
• Most common: 5–10 IV ozone treatments over 2–10 weeks
• Most benefit: 11–50 over 3–26 weeks

Generally, practitioners don’t do more than 2–3 IVs on the same patient per week.  

Most practitioners find it is best to start a new patient at a low dose and wait at least a few days to see how they respond.  

There isn’t a clear cut amount of treatments that will work.  Each patient is different and the practitioner is responsible for monitoring their response to the patients.  Some patients will benefit greatly from one treatment while others may require it weekly.

Patients can do ozone therapy via rectal or vaginal insufflation daily at home.  This is a great adjunctive to IV ozone, making the therapy more effective and a good standalone therapy.

How much does IV ozone therapy cost to the patient?

Here are common pricing structures:

• MaH — $150–$300
• HiDose — $400–$700
• 10 Pass — $700–$1,500
• EBOO — $800–$1,800

Details on the different forms of IV ozone treatments

Each IV ozone therapy has the same patient preparation and discharge instructions:

Patient Prep

1. Informed consent
2. Hydration
3. Avoid lots of coffee or things that thicken the blood
4. Avoid antioxidant supplements at least 2 hours prior to treatment

Patient discharge

1. Hydration
2. Avoid antioxidant supplements for at least 30 minutes after treatment
3. If patient feels unwell after treatment avoid further ozone therapy treatments until they feel better

Major Autohemotherapy (MaH) Protocol

Major autohemotherapy ozone involves drawing out 60–300mL of the patient's blood into a syringe or bag that has been pre-heparinized with 1,000 units.  The blood is then mixed with a 1:1 ratio of ozone gas at 20–60 ug/ml and dripped back to the patient at 2–5 drops per second.

The total MaH treatment takes 20–40 minutes.

You can find the protocol, equipment needed, and more information here.

High Dose (HiDose) Ozone Therapy Treatment

High dose ozone therapy involves the drawing out of 300mL of the patient’s blood into a special ozone bag.  There are two pumps used during the process — one for blood and one for saline — to make the process easier and quicker.

The blood is drawn from the patient into the bag along with saline and heparin.  Then, high dose ozone treatment is infused into the blood bag for about 3–5 minutes.

High dose IV ozone is most commonly used after a patient has undergone standard IV ozone (MaH) and responded well.

High dose ozone therapy clinics in Los Angeles are the easiest to find.

Total treatment time is usually 40–60 minutes.

EBOO Ozone Treatment (Extracorporeal Blood Oxygenation and Ozonation)

EBOO ozone therapy involves two lines in the patient simultaneously.  EBOO ozone treatment is administered as blood is drawn from one arm, mixed with ozone, and pumped back into the other arm.  

EBOO ozone therapy price is often in the $800–$1,800 range, with some practitioners charging even more. 

EBOO machines for sale are usually in the $15,000 to $60,000 range.  It involves pumps and an ozone machine.  From there, the practitioner also needs the IV lines and gas exchange unit (EBOO filter) for each therapy, costing $70–$150 before labor.  EBOO therapy machines are not FDA–approved.

A common misnomer is “EBOO dialysis”, as it is not performing a dialysis therapy.  A dialysis filter is often used for the purposes of mixing the ozone with blood which confuses people into thinking it is dialysis therapy plus ozone therapy. 

People seem to believe that EBOO therapy benefits are stronger than MaH.  But since this is usually based on the practitioner's experience and the patient's anecdotes, no official data exists to verify this belief.  EBOO does certainly have a stronger placebo effect potential than MaH, considering the visual factor of watching dark blood come out and bright red blood go back in.

Total time per EBOO ozone blood dialysis is usually 45–90 minutes.  EBOO therapy is the most labor intensive and nuanced ozone therapy treatment, requiring constant monitoring by the practitioner.

Ozonated Saline IV Therapy 

Ozonated saline treatments involve infusing saline mixed with ozone into the patient.

It is perhaps the form of ozone therapy that’s most prone to misadministration

It is VITAL that the saline bag is not used during the ozonation process.  The ozone does not react instantly with saline (like it does blood), so it will travel to the edges of the bag and break down plastics.  The plastics will then be infused into the patient.

A glass saline bubbler is necessary for proper ozonated saline technique for two reasons:

1. It allows for proper concentrations of ozone.  Just infusing a couple syringes into a saline bag does not work.
2. It prevents the breakdown of plastic and introducing microplastics to the patient

10 Pass Ozone Therapy

This technique of ozone therapy involves drawing out 200–300mL of blood from the patient, infusing it with ozone, and readministering to the patient — repeated ten times (hence the name). 

It involves a hyperbaric chamber where the blood is captured and mixed with the ozone gas.  It is unclear if this adds benefit to the therapy, but practitioners seem to get good results with 10 pass ozone treatments.

10 Pass Ozone is nearly as intensive to administer as EBOO ozone therapy, typically requiring the constant monitoring of a nurse or practitioner to ensure the therapy is running properly.

Notable mentions for ozone therapy treatments

Minor Autohemotherapy

Minor autohemotherapy is when a small amount of blood is drawn from the patient, mixed with ozone and then readministered via intramuscular injection.  Typically this only requires 10–20 cc of blood and 10–20 cc of ozone.  It is quite simple and has good benefits, such as seen by Dr. David Brownstein during a viral infection flurry. 

Rectal Ozone Therapy

Rectal ozone insufflation can be done at home up to five times per week, making it very valuable to the patient.  Patients can use this as a replacement for IV ozone or in adjunction for severe cases.  It has additional benefits for gut issues IV ozone doesn’t address. 

Vaginal Ozone Therapy

Vaginal ozone therapy can be done at home up to five times per week, making it very valuable to patients. They can use this as a replacement for IV ozone or in adjunction for severe cases. Vaginal ozone therapy has additional benefits for vaginal issues not addressed by IV ozone.