An Effective Treatment for Fibromyalgia? Exploring Ozone Therapy

Have fibromyalgia, or know someone who does? Several human studies have investigated ozone therapy as a potential complementary approach for fibromyalgia, reporting improvements in pain, fatigue, sleep, and quality of life. Although these findings are encouraging, further research is needed to establish its effectiveness and safety.

Understanding Fibromyalgia

Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive difficulties. It affects women more frequently than men and can significantly impact daily life.

Despite extensive research, its underlying causes remain incompletely understood. Researchers have investigated several contributing factors, including altered pain processing, immune dysregulation, metabolic abnormalities, and oxidative stress .

Oxidative stress occurs when reactive molecules exceed the body's ability to neutralize them and repair cellular damage. Researchers have also investigated mitochondrial dysfunction —abnormalities in the cellular structures responsible for energy production—as a potential contributor to fibromyalgia symptoms. Neither mechanism has been established as the sole cause of the condition.

Conventional treatment may include medications, individualized exercise, sleep management, and behavioral therapies. Because some patients continue to experience symptoms despite treatment, researchers are exploring additional approaches.

What Is IV Ozone Therapy?

Major ozone autohemotherapy involves collecting a measured amount of blood, exposing it to a controlled medical oxygen–ozone mixture in a specialized system, and returning it to the patient.

Researchers have proposed that this process may influence antioxidant defenses and cellular signaling. However, these proposed mechanisms do not establish that ozone therapy reliably improves symptoms or corrects mitochondrial dysfunction in people with fibromyalgia.

Important: Major ozone autohemotherapy is not the same as directly injecting ozone gas into a vein. Direct intravenous injection of ozone gas should not be performed. Ozone inhalation can damage the respiratory tract, and blood-handling procedures carry additional risks.

What Do Human Studies Show?

Several clinical studies have investigated ozone therapy in fibromyalgia. Their findings are promising, but the strength of evidence varies.

2019: Study involving 65 patients

Tirelli and colleagues reported that more than 70% of 65 patients experienced symptom improvement exceeding 50% after ozone-based treatment. Participants received different administration methods, including ozone autohemotherapy and rectal insufflation. Because the study lacked a control group, the results cannot establish that ozone caused the improvements.

Reference: Tirelli U, et al. European Review for Medical and Pharmacological Sciences. 2019;23(4):1786–1788.

2021: Physical function and quality of life

A prospective study involving 40 patients evaluated outcomes after 13 sessions of major ozone autohemotherapy. Researchers reported improvements in the Fibromyalgia Impact Questionnaire (FIQ) and SF-36, which measure fibromyalgia-related symptoms and broader health-related quality of life. The study did not include a control group.

Reference: Gazioğlu Türkyılmaz G, Rumeli Ş, Bakır M. Alternative Therapies in Health and Medicine. 2021;27(5):8–12.

2022: Study involving 200 patients

Researchers reported substantial improvements in pain and musculoskeletal function after oxygen–ozone autohemotherapy, with approximately 76% of participants described as experiencing considerable recovery. However, this was an uncontrolled case study, so the results require confirmation in controlled trials.

Reference: Tirelli U, et al. European Review for Medical and Pharmacological Sciences. 2022;26(21):7974–7979.

2023: Randomized, placebo-controlled trial

A randomized, double-blind study involving 54 patients compared ozone therapy as an add-on treatment with a placebo procedure over 10 sessions. The researchers reported improvements in selected fatigue-related measures and sleep quality. However, the difference between groups in the overall FIQ score was not statistically significant.

This trial provides a more rigorous assessment than uncontrolled studies, but its findings do not establish an overall benefit for fibromyalgia.

Reference: Sucuoğlu H, Soydaş N. Journal of Back and Musculoskeletal Rehabilitation. 2023;36(2):357–366.

2025: Follow-up extending to six months

A retrospective study evaluated 25 patients who completed 10 sessions of major ozone autohemotherapy. Average pain scores decreased from 6.4 before treatment to 3.68 afterward and remained lower at 4.12 six months later. FIQ scores also improved and remained below baseline at follow-up.

These findings suggest that improvements persisted in this small group, but the uncontrolled design cannot establish that ozone therapy caused them.

Reference: Üşen A, et al. Rheumatology International. 2025;45:72.

What Can We Conclude?

Human studies have reported improvements in selected fibromyalgia symptoms following ozone autohemotherapy, including pain, sleep, fatigue, physical function, and quality of life. Some studies also report that improvements persist during follow-up.

However, much of the evidence comes from small or uncontrolled studies. The randomized placebo-controlled trial found improvements in selected outcomes but did not demonstrate a significant advantage for the overall FIQ score. Larger, well-designed clinical trials are needed to determine effectiveness, appropriate protocols, and long-term safety.

Despite the lack of effective conventional treatments, ozone therapy remains an investigational or complementary approach and should not replace conventional care for Fibromyalgia.

Dr. Wilson's Experience with Ozone and Prolozone Therapy

Dr. Devin Wilson, ND, received certification in ozone and prolozone therapy from The American Academy of Ozone Therapy and was trained by Frank Shallenberger, MD, in 2012. Dr. Wilson has incorporated these approaches into his clinical practice since that time, emphasizing individualized care and consideration of potential benefits, limitations, and risks.

Medical disclaimer: This article is for educational purposes only and does not replace individualized medical advice. Evidence for ozone therapy varies by indication and administration method, and many proposed benefits require further clinical investigation. Ozone must never be inhaled, as it can cause serious lung injury. Direct intravenous injection of ozone gas is unsafe and should not be performed. Patients should discuss potential benefits, risks, and alternatives with a qualified healthcare professional.