Ozone therapy has been used in German and Italian clinical medicine for decades, dismissed by the FDA since 2019, it is now the subject of growing peer-reviewed research.
Ozone (O3) is the smell of a thunderstorm — that sharp, faintly metallic note in the air just before the rain arrives. It forms when ultraviolet light or electrical discharge breaks apart oxygen molecules in the upper atmosphere and the fragments recombine into a three-atom configuration less stable than the original. The ozone layer is named for it; smog alerts reference it; scientists track its stratospheric depletion with satellites. The same molecule, generated fresh from pure oxygen using an electrical generator in a clinical setting, is now being infused into people’s bloodstreams at integrative medicine practices from Beverly Hills to Manhattan, accumulating a body of peer-reviewed research that is more substantial, and more interesting, than its current public reputation would suggest.
On a 2023 episode of The Art of Being Well, the podcast hosted by functional medicine practitioner Dr. Will Cole, Gwyneth Paltrow described her experience with rectal ozone insufflation — the delivery of ozone gas into the colon via catheter — and acknowledged that it was “pretty weird,” but said it had been “very helpful.” The response followed a familiar arc: gastroenterologists objected on social media, the FDA’s 2019 warning resurfaced in dozens of articles, and the word ‘rectal’ did considerably more work in the coverage than the underlying clinical question merited. There’s a conversation worth having, though, and not about that delivery method specifically. But, rather, about what ozone therapy is, what the evidence does suggest, and why the medical establishment’s most-cited objection to it does not map cleanly onto the version of the treatment that researchers have been studying for the last decade.
From the stratosphere to the clinic
Medical ozone is generated by practitioners on-site — it degrades in minutes and cannot be stored or shipped — using a device that passes pure oxygen through an electrical field, converting a fraction of the O2 into O3. The gas is then administered in one of several forms: most commonly, mixed with a sample of the patient’s blood and reinfused intravenously in a process called major autohemotherapy (MAH); or delivered via rectal, vaginal, or ear insufflation; or applied to the skin under a sealed covering in a technique sometimes called an ozone sauna; or injected directly into joints as prolozone. (Inhaling it is not an option — ozone gas causes acute injury to lung tissue, even in low concentrations, which is where the FDA warning has its clearest application.)
Europe arrived at the clinical use of ozone roughly a century ahead of the American wellness market. German physicians used it to disinfect wounds during World War I; by the latter half of the 20th century, Germany, Italy, Russia, and Cuba had developed formalized ozone therapy protocols, and both Germany and Italy had integrated the treatment into their national healthcare systems. In the United States, the FDA issued a warning in 2019 stating that “ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy.” That warning applies broadly to all medical uses of ozone, though it was written with inhaled ozone primarily in mind. Whether a practitioner can legally offer ozone therapy in the U.S. depends on the state — a patchwork of naturopathic and integrative medicine licensing regulations governs access across the country.
The market, however, has not waited for regulatory resolution. According to Research and Markets, the global ozone therapy session market was valued at $1.5 billion in 2025 and is projected to reach $2.49 billion by 2030, growing at 10.9 percent annually. The therapy has become a fixture in the longevity and biohacking ecosystem — the same market that mainstreamed IV NAD+, hyperbaric oxygen, and peptide injections — where Gary Brecka, the human biologist whose protocols caught broad attention after UFC CEO Dana White credited him publicly with reversing his own health, includes ozone therapy as one of several anti-inflammatory and immune-modulating tools in his Superhuman Protocol.
What the research shows
The mechanism behind major autohemotherapy is not simply oxygenation. When ozone contacts blood, it reacts with lipids in the plasma to form signaling molecules — primarily lipid ozonation products — that activate the body’s own antioxidant defense systems. Glutathione rises. Superoxide dismutase increases. The result is a controlled, transient oxidative challenge that proponents describe as training the immune system and attenuating chronic inflammation over time, a process more analogous to the acute stress of exercise than to the sustained oxygen saturation of hyperbaric therapy. The research base has grown in direct proportion to the market.
A recent study published in Frontiers in Medicine examined major ozone autohemotherapy in patients with post-COVID syndrome and found significant improvements in fatigue, cognitive function, and overall quality of life in the treatment group. A 2025 retrospective study in MDPI followed 96 patients with mild cognitive impairment through a standard MAH protocol and documented measurable improvement in both olfactory function and cognitive performance. A separate 2025 study found positive short- and medium-term effects on pain, fatigue, and sleep disturbances in fibromyalgia patients. These are retrospective cohort studies and pilots — not large-scale randomized controlled trials — a limitation that researchers themselves are careful to flag and that the field acknowledges as the next necessary step.
“There may potentially be a role for ozone therapy someday, but right now it hasn’t been studied enough,” Vickram Tejwani, MD, a pulmonologist at the Cleveland Clinic, noted in Cleveland Clinic’s Health Essentials. “We need more data on the potential side effects, which could be severe, before we start offering it as a mainstream therapy or treatment.” He acknowledged the theoretical basis for efficacy in the same piece: “Ozone therapy functions like an antioxidant or anti-inflammatory. It could potentially be used for any type of inflammation, whether in a wound or related to conditions such as diabetes or arthritis.”
What a session involves
Major autohemotherapy, offered through a licensed integrative or naturopathic physician, involves a consultation, a blood draw of approximately 100 to 200 mL, contact with medical-grade ozone in a sealed glass bottle, and reinfusion via IV. The full process takes 45 minutes to an hour. A single session typically costs between $150 and $500 depending on the clinic and location; practitioners familiar with European protocols generally recommend a course of four to eight sessions for chronic conditions, based on the treatment schedules documented in the clinical literature. Prolozone — ozone injected directly into joints — is a separate application, used primarily for musculoskeletal pain, and practiced by physicians with specific training in the technique.
The clinics now offering MAH extend well beyond integrative medicine into the broader longevity and performance market, and that adjacency complicates the evaluation: a therapy administered in a credentialed clinical setting with documented protocols and follow-up looks meaningfully different from the same label attached to a wellness add-on without medical oversight. The version of ozone therapy that has a century of European clinical history, a growing body of peer-reviewed research, and a $1.5 billion global market is the IV version — the one that requires a physician, a blood draw, and a protocol. The version that made headlines when Paltrow mentioned it on a podcast is a different delivery method entirely. One version is, as she put it, pretty weird. The other is something the research seems to be steadily and methodically working out.
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