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Knee Ozone Injection Protocol
Landmarks, injection angle, gas volume and schedule for ozone knee injections, with the Prolozone mixture and ozone-oxygen approaches side by side.
Quick answer: Ozone knee injection uses 5–20 mL of gas (Wright) at 8–20 µg/mL (Madrid). Madrid gives 2 sessions a week for 4–6 sessions, and Wright repeats every 10–14 days. The sheet compares the Prolozone mixture and ozone-oxygen approaches.
Warning
Requires hands-on training from an experienced physician
Knee ozone injection should only be performed by a practitioner trained in it by an experienced physician.
Practitioner-only procedure. Injecting ozone, with or without a nutrient mixture, is done by trained, licensed clinicians. This sheet is a reference for them. It is not a self-treatment guide and not medical advice. Strict sterile technique is required every time.
What are the basics of ozone knee injection?
- Intra-articular knee injection places the solution and then ozone gas inside the joint capsule. Madrid lists pain, inflammation (arthritis, bursitis, tendinitis) and degenerative change (osteoarthritis, tendinosis) as indications, as a definitive treatment or a bridge while waiting for surgery.
- Prolozone, as Dr. Jeff Wright teaches it, adds nutrients and ozone to damaged tissue. His explanation: swollen tissue receives less blood, which leaves the area short of oxygen, and ozone supplies bioavailable oxygen.
- Wright's expected course from his own practice: a second injection 10 to 14 days after the first, with results after as few as 3 injections or as many as 6 to 8. Chronically ill patients can need more. He describes his success as 90 to 95 percent. That is his clinical impression, not a trial result.
- Wright's tutorials do not state ingredient amounts. The solution he used is a compounded pre-mix of methylcobalamin (vitamin B12), pyridoxine (vitamin B6), dextrose and procaine. The amounts are in the table below, taken from the compounded formula sheet. He also describes drawing up individual nutrients in a hood.
- The Madrid Declaration describes ozone-oxygen infiltration only: no nutrient mixture. Both are shown side by side below and labeled.
Sources: Dr. Jeff Wright's tutorial videos for MediSkill; Madrid Declaration on Ozone Therapy, 4th edition (ISCO3, 2025), sections 1.12 and 4. Paraphrased.
What dose and technique are used for ozone knee injection?
Two approaches are shown side by side. They are different procedures: the Prolozone mixture is Wright's, and ozone-oxygen alone is what Madrid describes.
| Prolozone mixture (per Wright) | Ozone-oxygen only (per Madrid) | |
|---|---|---|
| What goes in | Dr. Wright's pre-mixed solution (formula below) first, then ozone gas through the same needle. | Ozone-oxygen mixture only. |
| Gas volume | 5 to 20 mL of ozone gas, depending on the knee and the person. In the demonstration a healthy young man took the full 20 mL. | 10 to 15 mL (section 4.8). Madrid's general joint table gives 5 to 20 mL. |
| Concentration | Not stated in the tutorial. | 8, 10 or 20 µg/mL (section 4.8). The joint table gives low 5, medium 10, high 15 to 20 µg/mL. |
| Approach | About one finger or thumb width below the point where a line drawn perpendicular from the kneecap meets a soft spot. Needle at about 30 degrees. | Lateral: patella positioned laterally, needle at about 45 degrees into the space between patella and femur (commonly used). Medial: needle horizontal, middle of the joint at the lower half of the patella. Anterior: knee flexed 60 to 90 degrees, needle beside the patellar tendon and parallel to the tibial plateau. |
| Schedule | Second injection 10 to 14 days after the first. Results in as few as 3 and as many as 6 to 8 injections. | Twice a week, 4 to 6 sessions. |
Dr. Wright's pre-mixed solution: how it is made (per 8 mL of mixture)
This is the compounded mixture Dr. Wright used in his protocols. The amounts below are the recipe for making the mixture, taken from the compounded formula sheet, not from the tutorial videos. They are not the amount injected at one site.
| Ingredient | Strength | Amount per 8 mL of mixture |
|---|---|---|
| Methylcobalamin (methyl-B12) | 1 mg/mL | 2 mL |
| Pyridoxine (vitamin B6) | 100 mg/mL | 1 mL |
| Dextrose | 50% | 1 mL |
| Procaine | 2% | 4 mL |
| Total | 8 mL |
- Draw up the solution into a sterile syringe using antiseptic technique (the formula sheet uses a 10 mL syringe).
- Inject the solution at the selected site, using this sheet's own technique and volume.
- Leave the needle in place, remove the syringe, and inject the ozone through the same needle.
How much is injected is not stated in Dr. Wright's knee tutorial, so this sheet gives no solution volume.
This is a compounded pre-mix with a beyond-use date of 90 days refrigerated. The solution is compounded by a pharmacy and requires a prescriber.
Madrid advises placing any local anesthetic so that the ozone does not break it down. Dr. Wright gives his solution first and then the ozone through the same needle. These are two different practices.
Needle gauge for the knee is not stated in the tutorial or in Madrid's knee section, so none is given here.
What are the best tips when using ozone knee injection?
- Wright's aftercare advice after a knee injection: normal daily activities and walking stairs are fine. He would not have the patient go skiing or do martial arts.
- Once the needle is through the skin there should be little discomfort, and the solution should push in easily. Wright stabilizes the needle, removes the first syringe and attaches the ozone syringe.
- Feel the side of the kneecap while the gas goes in. Wright can feel, and hear, the gas in the joint. The patient says when pressure becomes too much.
- After the needle is out, move the knee passively so the solution and gas spread around the joint.
- Tell the patient what to expect. Pressure and fullness while the gas goes in are normal, and the patient should say when it is too much. Wright says an electrical zing is not normal: stop and reposition.
What are the precautions for ozone knee injection, and who should avoid it?
- Sterile technique every time. Madrid says most serious side effects trace back to malpractice, including technique, asepsis and antisepsis. Its reported serious events include septic arthritis of the knee after intra-articular infiltration, abscess after paravertebral injection, and one death from sepsis after a paravertebral infiltration done without proper asepsis (Madrid Declaration on Ozone Therapy, 4th edition (ISCO3, 2025), section 2.5).
- Clean the injection site with alcohol and let it dry before the needle goes through (as Dr. Wright does). Use sterile, single-use syringes and needles, and do not touch the vial adapter once it is out of its package (Wright).
- Draw up nutrient solutions in a hood with needleless vial adapters, as Dr. Wright demonstrates in his overview video. Check that every solution you inject is allowed by your licensing board, as he advises.
- Never inject ozone gas into a vein or an artery. Madrid strongly discourages both because of the risk of air embolism, and lists embolic events after paravertebral and intradiscal injections among its serious adverse events.
- Septic arthritis of the knee after intra-articular infiltration is on Madrid's list of serious events. Aseptic technique at the joint is the main safeguard.
Contraindications
The Madrid Declaration lists these contraindications for systemic ozone (IV and blood). It gives no separate list for intra-articular injection, but many practitioners use the same screening before treating:
- Direct inhalation of ozone gas. The fluid lining the lungs has no antioxidants to buffer it, so inhaled ozone is toxic.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency (favism, acute hemolytic anemia). Madrid lists it as a contraindication for systemic ozone, but whether it is absolute is debated. MediSkill protocols start low and go slow; see the contraindications article.
- Toxic hyperthyroidism (severe Graves' disease)
- Thrombocytopenia (platelets under 50,000) and severe coagulation disorders
- Severe cardiovascular instability
- Acute alcohol intoxication
- Recent acute myocardial infarction
- Acute massive hemorrhage
- Convulsive states
- Hemochromatosis
- Patients receiving intravenous copper or iron therapy
Pregnancy. Madrid advises avoiding ozone therapy in the first trimester (weeks 0 to 13) and reserves its use in pregnancy for specialists in gynecology and obstetrics.
More detail
Landmarks and steps, as demonstrated by Dr. Wright
- Find the patella. Draw a line perpendicular from the kneecap. There is a soft spot there.
- Go one finger or thumb width down. This is the injection site.
- Clean the landmarks with alcohol and let them dry.
- Enter at about 30 degrees. The needle should slide into the knee.
- Inject the solution. Stabilize the needle, swap the syringe, attach the ozone syringe and inject 5 to 20 mL of gas while the patient reports pressure.
- Remove the needle and move the knee passively.
Equipment
- Sterile syringes and needles (gauge not stated for the knee)
- Dr. Wright's compounded pre-mixed solution (requires a prescriber), or individual nutrients drawn up in a hood with needleless vial adapters
- Ozone-oxygen gas in a syringe (generator, medical-grade oxygen)
- Alcohol prep
What the studies used
Study doses are listed as printed in each paper and are not Madrid or Wright dosing.
- In a double-blind trial against placebo (air injection) in 96 people with knee osteoarthritis, ozone gave lower pain at 16 weeks (VAS 1.7 vs 4.8, p<0.001). It used 20 µg/mL, 10 mL, weekly for 8 weeks (Lopes de Jesus 2017).
- In 141 people, ozone at 30 µg/mL, 10 mL, weekly for 3 weeks, gave about the same pain relief at 6 months as hyaluronic acid (VAS 7.6 to 2.6 vs 7.1 to 3.0, no significant difference) (Raeissadat 2018).
- In 96 people, ultrasound-guided ozone (10 to 20 µg/mL, 10 mL, weekly for 3 weeks) and a corticosteroid injection both lowered WOMAC by about 35 points at 12 weeks, with no difference between them (Aslan 2024).
- The closest study to a mixture: in 60 people, dextrose 50% plus somatropin with ozone gave a better WOMAC at week 16 than the same mixture without ozone (41.3 vs 49.2), under fluoroscopy, in three injections (Imani 2020).
Knee is the best-studied area, with several randomized trials. No human study of the classic Prolozone mixture (procaine, vitamins and ozone) is in the study summary we drew on. Trials that add something to ozone used dextrose, somatropin or hypertonic saline, and the evidence for Wright's mixture itself rests on his clinical experience.
Video
Overview of the technique and the reasoning behind it: Prolozone Overview - Ozone Joint Injections | Dr. Jeff Wright.
Learn more
Background, benefits and research on injections: Ozone injections, full article. Research: Ozone injections for knee osteoarthritis, 2025 study.
Related protocols: Hip Ozone Injection Protocol, Shoulder Ozone Injection Protocol, Elbow Ozone Injection Protocol.
Other injection protocols
For licensed practitioners. Educational reference only, not medical advice. Follow your scope of practice and local regulations.
