Clear-acrylic hyperbaric oxygen chamber in a calm modern clinic, soft teal and white palette, no people

Hyperbaric Oxygen Shows Early Promise in Drug-Refractory Ulcerative Colitis

A small clinical trial from the Netherlands has added ulcerative colitis to the growing list of conditions researchers are testing hyperbaric oxygen therapy against — and the early signal is cautiously encouraging. Among 16 patients whose disease had resisted multiple advanced drugs, a course of hyperbaric oxygen was well tolerated and, in a meaningful minority, reopened a path toward remission that medication alone had closed.

The findings, published in the Journal of Crohn’s and Colitis, come from a phase 2a pilot study — the earliest stage of human efficacy testing. They should be read as a hypothesis worth pursuing, not as evidence that hyperbaric oxygen belongs in routine colitis care. Hyperbaric oxygen is not cleared by the U.S. Food and Drug Administration for inflammatory bowel disease, and the researchers themselves frame the work as preliminary.

Why researchers are looking at oxygen for colitis

Ulcerative colitis is a chronic inflammatory disease of the colon, and for a subset of patients no drug class holds the inflammation down. When biologics and other advanced therapies fail one after another, the remaining option is often surgery to remove the colon. That is the population this trial targeted: people who had already run out of good pharmaceutical choices.

The rationale for oxygen rests on the biology of the inflamed bowel. Hyperbaric oxygen therapy involves breathing 100% oxygen inside a pressurized chamber, which dramatically raises the amount of oxygen dissolved in the blood and delivered to tissue. In poorly perfused, inflamed intestinal wall, the researchers reasoned, that oxygen boost might promote new blood-vessel growth and tissue repair — a regenerative mechanism distinct from the anti-inflammatory drugs that define standard treatment.

What the trial did

Between January 2023 and December 2024, investigators led by Lieven Mulders, MD, of Amsterdam UMC enrolled 16 patients aged 16 and older with moderate-to-severe ulcerative colitis — a total Mayo score of at least 5 and an endoscopic subscore of at least 2 — who had failed at least two classes of advanced therapy and stayed on stable background medication.

Treatment was delivered in supervised multiplace hyperbaric chambers at 2.4 atmospheres absolute for 120 minutes per session, on consecutive weekdays. Patients were assigned in sequence to receive 10, 20, or 30 sessions. The team never ran the 30-session group: the 20-session cohort had already cleared the study’s prespecified bar of at least a 50% response rate, so further dose escalation was unnecessary.

The primary endpoint was demanding — a combined clinical and endoscopic response at week 12, requiring a drop of at least 3 points and 30% in the total Mayo score, a rectal bleeding subscore of zero, and a measurable improvement on endoscopy.

The results

At 12 weeks, 38% of patients overall met that strict combined endpoint (95% confidence interval, 18–61). The dose pattern was the most striking part: 25% responded after 10 sessions, but 50% responded after 20, hinting that duration matters.

Broader measures moved in the same direction. Clinical response reached 56%, symptomatic remission 44%, and histologic remission 19%, with the average patient’s total Mayo score falling by 4.3 points. Imaging supplied a mechanistic clue: contrast-enhanced and standard intestinal ultrasound showed responders gaining bowel perfusion and keeping their bowel-wall thickness, while non-responders lost both. The divergence supports the idea that hyperbaric oxygen was acting on blood flow and tissue repair rather than simply damping inflammation.

On safety, the therapy held up well through 26 weeks. The most common side effects were fatigue, temporary worsening of colitis symptoms, and nasopharyngitis. No serious adverse events occurred, and no one stopped treatment because of side effects.

Read the limits before the headline

The reasons for caution are substantial, and the authors list them plainly. This was an open-label, single-center study of just 16 people, with no placebo or sham-treatment group — a design that cannot rule out a placebo effect, which runs high in inflammatory bowel disease trials. Because patients were assigned to dose cohorts in sequence rather than at random, differences between the groups could have skewed the apparent dose-response. And the approach leans on specialized hyperbaric facilities and advanced ultrasound expertise that most gastroenterology practices do not have.

There is also the regulatory reality. The FDA clears hyperbaric oxygen for a defined set of indications — including decompression sickness, certain non-healing wounds, and carbon monoxide poisoning — and ulcerative colitis is not among them. In 2025 the agency reminded clinicians and patients to use hyperbaric devices only as directed, citing safety risks including fire hazard in the oxygen-rich chambers. A promising pilot does not change that standing.

What comes next

The value of a phase 2a trial is that it justifies a bigger, more rigorous one — and that work is already underway. A multicenter, randomized, double-blind, sham-controlled trial of hyperbaric oxygen for ulcerative colitis is enrolling patients at U.S. sites, the kind of study that can separate a true treatment effect from expectation. Until results like those arrive, hyperbaric oxygen for colitis remains investigational: a mechanism with a plausible story and an early, imperfect signal, awaiting the controlled evidence that would tell patients and physicians whether it genuinely works.

Sources

← Back to blog