Fibromyalgia and Multiple Sclerosis: Shared Biological Pathways and the Search for New Treatments

Fibromyalgia and multiple sclerosis (MS) are very different conditions, but researchers are investigating whether certain biological processes—including oxidative stress, mitochondrial dysfunction, and immune dysregulation—may contribute to both. These overlapping mechanisms have also prompted interest in therapies that could influence the body's antioxidant and immune responses, including medical ozone therapy.

Could ozone therapy have a role in managing these conditions? Early human studies offer some intriguing findings, but the evidence remains preliminary and more rigorous research is needed.

Fibromyalgia: Chronic Pain, Fatigue, and Altered Pain Processing

Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, nonrestorative sleep, cognitive difficulties, and increased sensitivity to pain. It affects women more frequently than men and can significantly interfere with daily activities and quality of life.

Despite extensive research, the condition does not have one clearly established cause. Current evidence suggests that several factors may interact, including altered central nervous system pain processing, genetic susceptibility, sleep disturbances, stress responses, and changes in autonomic and immune function.

Oxidative stress and mitochondrial dysfunction have also been investigated as potential contributors. However, neither has been established as the single underlying cause of fibromyalgia.

Treatment typically involves a personalized combination of physical activity, sleep management, psychological or behavioral therapies, and medications when appropriate. Because symptoms can persist despite conventional treatment, researchers continue to investigate additional approaches.

Multiple Sclerosis: Immune-Mediated Damage to the Nervous System

Multiple sclerosis is a chronic inflammatory disease of the central nervous system. In MS, immune-mediated processes damage myelin—the protective covering around nerve fibers—and may also injure the underlying nerve cells and axons. Symptoms vary considerably and may include fatigue, visual disturbances, weakness, numbness, balance difficulties, and impaired coordination.

The causes of MS are complex. Genetic susceptibility, environmental exposures, prior infection with Epstein-Barr virus, and abnormal immune responses are among the factors implicated in its development.

Oxidative stress and mitochondrial dysfunction have also been studied in MS because they may contribute to inflammation, impaired energy production, and damage to vulnerable nerve cells. These mechanisms are relevant areas of research, but they do not fully explain the disease.

Treatment depends on the individual's disease course and symptoms. Disease-modifying therapies can reduce inflammatory disease activity and the risk of relapses in appropriate patients. Other treatments may address acute relapses, rehabilitation needs, and specific symptoms.

Could These Conditions Share Biological Pathways?

Although fibromyalgia and MS differ substantially in their underlying disease processes, some biological pathways may overlap.

Oxidative stressoccurs when the production of reactive molecules exceeds the body's ability to neutralize them and repair the resulting damage. Reactive oxygen species are not inherently harmful; they also participate in normal cell signaling. Problems can arise when their production and removal become imbalanced.

Mitochondriaare structures within cells that produce much of the energy needed for normal cellular function. Oxidative damage and mitochondrial abnormalities may interfere with energy production and other cellular processes. Researchers have investigated these changes in both fibromyalgia and MS, although the extent to which they drive symptoms or disease progression remains uncertain.

Immune dysregulationis another area of interest. In MS, immune-mediated inflammation is central to disease pathology. In fibromyalgia, researchers have explored possible immune and inflammatory contributions, but the condition is not generally classified as a conventional autoimmune disease.

These similarities provide a scientific rationale for investigating treatments that influence redox signaling or immune activity. They do not establish that the conditions have the same cause or will respond to the same treatment.

What Is Ozone Therapy?

Medical ozone therapy uses a carefully controlled mixture of ozone and oxygen. In major ozone autohemotherapy, a measured amount of blood is collected, exposed to the ozone-oxygen mixture in a specialized closed system, and returned to the patient. This is different from directly injecting ozone gas into a vein, which should not be performed.

Ozone is a potent oxidizing agent. In the controlled conditions used in ozone research, its interaction with blood components can produce signaling molecules that may influence the body's antioxidant and cellular stress responses. Researchers have proposed that these reactions may affect antioxidant pathways, inflammatory signaling, and immune-cell activity. However, proposed mechanisms should not be confused with demonstrated clinical benefits. It has not been established that ozone therapy reliably restores mitochondrial function, improves oxygen delivery to tissues, or produces lasting disease modification in people with fibromyalgia or MS.

Human Research: Ozone Therapy and Fibromyalgia

Several human studies have investigated ozone therapy for fibromyalgia, with preliminary findings involving pain, sleep, fatigue, and quality of life.

Randomized, double-blind, placebo-controlled study

Sucuoğlu and Soydaş, published in 2023, evaluated ozone therapy as an add-on treatment in a randomized, double-blind, placebo-controlled study involving 54 patients. Participants received 10 sessions of major and minor autohemotherapy or placebo treatment.

The ozone group showed improvements in selected fibromyalgia questionnaire subscales, including fatigue-related measures, and in sleep-quality scores. However, the change in the overall Fibromyalgia Impact Questionnaire score was not significantly different between the ozone and placebo groups.

This distinction is important: although some outcomes were encouraging, the study did not demonstrate a significant advantage over placebo for the overall fibromyalgia impact score.

Reference: Sucuoğlu H, Soydaş N.Efficacy of ozone therapy as an add-on treatment in fibromyalgia: A randomized double-blind placebo-controlled study.Journal of Back and Musculoskeletal Rehabilitation. 2023;36(2):357–366.

Observational study involving 65 patients

Tirelli and colleagues reported outcomes in 65 patients treated at an Italian clinic. Most received ozone autohemotherapy, while a smaller group received rectal ozone insufflation. The authors reported that 45 patients—approximately 70%—experienced an improvement of more than 50% in symptoms.

These results are noteworthy but should be interpreted cautiously. The study did not include a control group, and the use of different treatment methods makes it difficult to determine how much improvement was specifically attributable to ozone therapy.

Reference: Tirelli U, et al.Ozone therapy in 65 patients with fibromyalgia: an effective therapy.European Review for Medical and Pharmacological Sciences. 2019;23(4):1786–1788.

More recent clinical observations

A 2025 retrospective study of 72 patients who underwent 10 sessions of major ozone autohemotherapy reported improvements in pain, fibromyalgia impact, quality of life, and sleep-related measures after treatment. Because the study retrospectively compared outcomes before and after treatment without a control group, it cannot establish that ozone caused the improvements or determine how durable they may be.

Reference: Tertemiz OF, et al.Effect of major ozone autohemotherapy in fibromyalgia syndrome: a retrospective study.PeerJ. 2025;13.

What does this mean?Human research in fibromyalgia includes a small randomized controlled trial as well as observational studies. The findings justify further investigation, particularly into pain, fatigue, and sleep, but they are not yet sufficient to establish ozone therapy as an effective treatment.

Human Research: Ozone Therapy and Multiple Sclerosis

Research into ozone therapy for MS is at an earlier stage. The human studies identified here have primarily investigated immune-cell activity and inflammatory signaling rather than whether treatment improves disability, reduces relapses, or slows disease progression.

Th17 cells and inflammatory signaling

A 2020 study examined 20 patients with MS who received ozone autohemotherapy twice weekly for six months. Researchers measured Th17 immune cells and related inflammatory markers before and after treatment.

Following treatment, the investigators reported reductions in the frequency of Th17 cells and in the expression of several associated inflammatory factors, including IL-17-related measures.

Th17 cells are involved in immune responses and have been implicated in MS-related inflammation. These results suggest that ozone autohemotherapy may influence selected immune markers. However, the study was not controlled, and changes in laboratory markers do not establish improvements in symptoms or disease progression.

Reference:Changes in Th17 cells frequency and function after ozone therapy used to treat multiple sclerosis patients.2020.

Regulatory T cells and immune regulation

A related human study published in 2021 examined 20 patients with relapsing-remitting MS who received ozone therapy twice weekly for six months. The researchers reported increases in regulatory T-cell frequency and changes in associated markers, including FoxP3, IL-10, and TGF-β.

Regulatory T cells help control immune responses and maintain immune tolerance. The findings provide additional preliminary evidence that ozone autohemotherapy may influence immune signaling in people with MS.

However, this study also lacked a controlled clinical comparison. It did not establish that the observed immune changes translated into fewer relapses, reduced MRI disease activity, improved neurological function, or slower disability progression.

Reference:The effects of oxygen-ozone therapy on regulatory T-cell responses in multiple sclerosis patients.2021.

What does this mean?These small, uncontrolled studies provide preliminary evidence of changes in selected immune markers. They do not establish ozone therapy as an effective treatment for MS, and larger controlled trials measuring clinical outcomes are needed.

Is Ozone Therapy a Shared Treatment for Fibromyalgia and MS?

The possibility that ozone therapy could influence biological pathways relevant to both conditions is an interesting area for further study. Research in fibromyalgia has reported improvements in selected symptoms, while research in MS has identified changes in immune markers.

However, these findings represent different types of evidence. Symptom changes in fibromyalgia do not establish that the same treatment will benefit MS, and changes in immune markers in MS do not prove clinical improvement.

Ozone therapy also involves specific procedural risks and requires careful attention to the administration method. Ozone gas must never be directly injected intravenously. Inhalation can injure the respiratory tract, and blood-handling procedures carry risks, including infection and complications related to vascular access. The safety of one protocol should not be assumed to apply to every route or dose.

For people living with fibromyalgia or MS, ozone therapy should not replace established care. In MS particularly, it should not be used as a substitute for evidence-based disease-modifying treatment.

Conclusion

Fibromyalgia and multiple sclerosis are distinct conditions, but oxidative stress, mitochondrial abnormalities, and immune signaling are among the biological processes being investigated in both.

Human studies of ozone therapy have produced preliminary findings in fibromyalgia and changes in selected immune markers in MS. These results are scientifically interesting and may provide support to patients that are not responding to conventional treatments.

Well-designed, adequately powered clinical trials are needed to determine whether ozone therapy offers meaningful benefits, which patients might benefit, how long any effects last, and what risks are associated with different protocols.

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.