IV Ozone Therapy: A Guide for Medical Directors

If you are the medical director being asked to approve IV ozone, this page is written for you. It covers what the treatment is, what the evidence does and does not show, who should not receive it, how the protocol runs, what oversight and documentation to put in place, and where state rules come in. A PDF packet with a standing-order template and checklists is available to go with it.

• The procedure: about 200 mL of the patient's blood is mixed with 200 mL of oxygen-ozone gas in a bag with 120 mL of saline and heparin, then returned by gravity.
• The limits: 1 to 2 IVs per week at most, a maximum of 70 gamma, medical oxygen only.
• The status: not FDA-approved for any disease or condition, so it is offered with informed consent and without disease claims.
• The rules: state medical and nursing boards set scope, delegation and supervision, and they differ. Links to every board are below.

What IV ozone (MAH) is, in clinical terms

IV ozone therapy, also called major autohemotherapy (MAH), is done in a clinic. A small volume of the patient's blood is drawn into a bag that holds saline and heparin. Medical-grade ozone and oxygen gas is added at a measured concentration, the bag is rocked gently, and the blood returns to the patient by gravity through the same IV, usually within 30 minutes. The ozone reacts with the blood in the bag. The gas is never infused into the vein.

Ozone is a strong oxidant. In the bag it reacts with the blood's antioxidants and lipids, and the patient receives a mild, brief oxidative signal. The proposed mechanisms include activation of the Nrf2 antioxidant pathway, higher red cell 2,3-DPG with better oxygen release, and immune modulation. The lungs have very little antioxidant protection in their lining fluid, which is why ozone is never breathed. This is a clinical overview, and the mechanisms are still being studied. The full background is in our IV ozone (MAH) article.

The evidence and the safety record

The honest summary is that the safety record is good when the procedure is done properly, and the evidence for benefit is limited and uneven. Most published work is small, uncontrolled, or from outside the United States. Larger randomized trials are still needed.

• Safety. The most-quoted figure comes from a survey of German ozone therapists (Jacobs, 1980), reported by the International Scientific Committee of Ozone Therapy (ISCO3). It covered about 5.6 million sessions given to 384,775 patients and found 336 complications, about 6 per 100,000 sessions (0.006%). The author judged that most were caused by technique errors, anticoagulant mistakes or unsterile handling rather than by the ozone. It is self-reported and more than 40 years old, so use it as a rough guide. See the safety article.
• Mechanism in humans. In a small controlled study in healthy volunteers, three MAH treatments at 35 µg/mL raised Nrf2 in blood cells and later increased superoxide dismutase and catalase activity (Re et al., 2014, Eur J Pharmacol).
• Clinical outcomes. In 40 patients with heart failure, 5 weeks of major and minor ozone therapy added to standard care lowered oxidative stress markers and NT-proBNP and modestly increased 6-minute walk distance. Ejection fraction did not change significantly, and the study had no randomized control arm (Buyuklu et al., 2017, Cardiovasc Toxicol).
• Cancer care. A review concluded that animal and laboratory work and isolated clinical reports suggest a possible adjuvant role, and that randomized trials are required before any claim can be made (Clavo et al., 2018, Evid Based Complement Alternat Med).
• Overview. A broad review of the pharmacology and uses of ozone therapy ends with the same call for more studies (Smith et al., 2017, Med Gas Res).

Nothing here supports a claim that ozone cures or treats a disease, and your marketing should not make one. For the FDA's position and what it means in practice, see our explainer on the FDA statement.

Patient selection: contraindications and considerations

This list matches the MediSkill IV ozone protocol. Absolute contraindications mean do not proceed. Considerations mean a physician decides, usually by starting low and monitoring.

The protocol at a glance

MediSkill trains clinics on the MAH protocol of Thomas Levy, MD. The full equipment list, step-by-step directions and dosing chart are on the IV ozone protocol page. The essentials:

Oversight and delegation

Most practices approach IV ozone as they do other IV therapies: trained clinical staff administer it under a supervising physician's standing order. The physician sets the protocol and patient-selection rules, is reachable for reactions, and reviews the program. State law decides who may do what, and this is where medical directors most often need to check.

A workable standing order names the route (MAH), who may administer, the screening and stop rules above, the dose range, titration and frequency limits, how reactions are handled, and what is documented at each visit. It has an effective date and a review date, and the medical director signs it. HiDose, 10-Pass and EBOO are different procedures and need their own orders. The sign-off starter PDF has a fill-in template.

Supervision models differ by state: on site, immediately available, or remote. Whether any of these applies to ozone specifically is a question for your board, so use the questions near the end of this page.

Informed consent and documentation

Because the therapy is not FDA-approved, consent matters more than usual. A sound consent form explains what the procedure is; says plainly that it is not FDA-approved for any disease or condition, is not guaranteed to help, and is not a standard-of-care procedure; lists the risks (bruising or bleeding at the site including from heparin, a temporary Herxheimer-type reaction, stinging at the site, phlebitis, infiltration, medication interactions, unforeseen reactions); offers alternatives including no treatment; states the cost and that insurance does not cover it; and records the patient's right to stop at any time. Release, hold-harmless and arbitration language varies in what courts will enforce, so have your attorney decide what to include.

At each visit, document the date, screening result, gamma, blood, saline and gas volumes, heparin dose, oxygen source, the patient's response and any reaction, the administering staff member, and that consent is on file. Capture screening answers before the first treatment, including pregnancy, heparin allergy, heart conditions, blood thinners and other medications, bleeding or clotting disorders, thyroid disease, seizure history, and known G6PD deficiency.

Recognizing and handling reactions

The most common reaction is a Herxheimer-type response, which comes from immune activation and pathogen die-off. Symptoms include headache, nausea, diarrhea, muscle pain, fatigue, fever, rash and swelling. It is usually managed by starting at a low dose, lowering the dose or spacing sessions, and having the patient feeling well before they leave. A chronically ill patient may feel worse after the first 2 to 4 treatments and better after that. Other effects include fatigue after too high a dose, headache, and anxiety about seeing blood. See the Herxheimer article.

• Procedural problems. If blood stops flowing, flush the line with saline both ways. If a clot is suspected and flow does not return, start a new IV site with new tubing and stop the first one. Use tubing without a filter, because a filter slows the blood and can cause clotting.
• Anything unusual, severe or rapid in onset. Stop the infusion, keep IV access, check vital signs, notify the medical director, and call 911 for an emergency. Write the plan down before the first patient and post it where staff can see it.
• After the reaction. Document it, adjust the dose or frequency per the protocol, and have the medical director review it.

Equipment and oxygen

Standard IV ozone needs an ozone generator, a medical oxygen cylinder with a regulator, a syringe fill system, an IV pole, and ozone-resistant disposables: four 60 cc silicone syringes, a safety scalp vein set, IV tubing without a filter, saline, heparin, and the usual IV supplies. The full list is on the protocol page. The MAH article puts a typical startup at around $10,000 for equipment and training.

• Medical oxygen only. Ozone given into the body must be made from medical oxygen. An oxygen concentrator and room air are not acceptable for IV use. Medical oxygen is obtained through a medical-gas supplier, and the supplier will tell you what documentation it needs. See oxygen for ozone therapy and how to get it.
• Blood goes in first. Saline bags are plastic that ozone degrades. Ozone gas must never go into a bag that has only saline in it. The blood has to be in the bag before the gas is added.
• Choose the generator carefully. Look for ozone-resistant materials in the gas path, a documented and verifiable concentration, service and support after the sale, and regulatory or certification claims you can verify in writing with the manufacturer. Our page on why you do not want a cheap ozone machine explains the reasons.

Compliant marketing

Because ozone therapy is not FDA-approved for any disease or condition, it cannot be promoted with disease-treatment claims. The answer to how to market it is positioning and consent, not advertising outcomes.

Some states restrict how non-FDA-approved therapies can be advertised, so have your attorney review website and social copy.

State rules

The FDA regulates drugs and medical devices. It does not regulate the practice of medicine. Each state's medical board and board of nursing set scope of practice, delegation, supervision and advertising rules for licensees, and a state may also regulate who may order or administer a given treatment. Those rules differ from state to state and change over time. This page and the PDF are educational and are not legal advice, so confirm everything with your board and a healthcare attorney.

We do not summarize state law here, because it would go out of date and we cannot verify 50 sets of rules. Instead, the table links to each state's official medical board and board of nursing. Links were checked on October 14, 2026; a few state sites block automated checks and may need a second try in your browser.

Medical boards and boards of nursing, by state

Questions to ask your board or a healthcare attorney

• May an RN administer ozone under a standing order, and may an MA or LPN take any part in the procedure, such as starting the IV?
• Must the supervising physician be on site, immediately available, or can supervision be remote?
• What must a valid standing order contain in this state, and how often must it be renewed?
• Is a specific informed-consent form or disclosure required for a therapy that is not FDA-approved?
• What advertising rules apply to a non-FDA-approved therapy, including website and social media posts?
• Does my malpractice policy cover ozone therapy, and what documentation will the carrier expect?

Next step

If you want to see the protocol taught live, book free IV Ozone 101. It is a live Zoom training for clinics, and medical directors are welcome on the call. The packet below is for the practice to hand to its medical director.

Frequently asked questions

Is IV ozone therapy FDA-approved?

No. Ozone therapy is not FDA-approved for any disease or condition. The FDA regulates drugs and devices. It does not regulate the practice of medicine, which is set by each state's medical and nursing boards. Offer it with informed consent and without disease claims.

Does the medical director need to be on site?

That depends on the state and on who administers the treatment. Some states require the supervising physician to be on site or immediately available, and others allow remote supervision. Ask your state medical board or a healthcare attorney.

Who can administer IV ozone?

In most practices the same people who run other IV therapies do it, under a standing order and delegation: RNs, NPs and PAs, or physicians. Whether an LPN or MA may take any part depends on state scope-of-practice rules.

Is G6PD testing required before IV ozone?

No routine testing is required. Ask about known G6PD deficiency (favism). For standard IV ozone it is a consideration: antioxidant capacity is lower, so start low, follow the titration and monitor. It is an absolute contraindication only for high-dose treatments (HiDose, 10-Pass and EBOO).

How often can a patient have IV ozone?

One to two IVs per week at most. A first series is usually 4 to 8 infusions, followed by maintenance, often about once a month, depending on the reason for treatment.

What kind of oxygen is required?

Medical oxygen from a cylinder. An oxygen concentrator and room air are not acceptable for IV ozone.

Does high blood pressure rule a patient out?

No. It is a consideration, not an absolute contraindication. A physician should review the patient's medications because heparin is part of the protocol.

How much does a session cost the patient?

IV ozone (MAH) generally costs $200 to $300 per session. Pricing varies by clinic and location.