Hyperbaric Oxygen Therapy for Ulcerative Colitis

This article is part of the IBD Index. Last updated on March 14, 2022.

I initially focused on either UC-specific or general IBD evidence, but hope to eventually update this post to include Crohn’s-specific evidence as well.

What is hyperbaric oxygen therapy?
Hyperbaric oxygen therapy (HBOT) involves inhaling 100% oxygen at greater than atmospheric pressure for a period of time, usually between 30-120 min. This is done either in a single-person pressurized chamber, or in a multi-person room where oxygen is delivered via hoods or masks. Treatments can take place in hospitals or outpatient clinics, or at home with soft hyperbaric oxygen chambers (although the efficacy of soft chambers is debated).

HBOT is most commonly used for refractory wound healing in situations like advanced diabetes, severe burns, and skin grafts, but it’s being investigated for therapeutic potential in a number of different conditions (including IBD!). Few clinical trials have been conducted so far, but the ones that have (plus the documented case studies) are extremely promising (see references below).

How might hyperbaric oxygen therapy help with IBD?
Several potential mechanisms are discussed in the literature and in HBOT marketing materials, but they all center around increasing blood and tissue oxygen levels.

Higher levels of oxygen lead to increased reactive oxygen species (ROS) and reactive nitrogen species (RNS), which may sound like a negative (after all, don’t ROS cause oxidative damage?), but these molecules actually have quite a few therapeutic effects, including increased synthesis of wound growth factors, mobilization of stem cells from bone marrow, diminished inflammatory response, and elimination of pathogenic bacteria and fungi. (Thom 2012, Wu 2021)

In UC, HBOT may help alleviate mucosal hypoxia, which is a hallmark of UC, as well as stimulate colonic stem cells to promote mucosal healing. (Bekheit 2016, Wu 2021)

Are there any risks?
The main risk of HBOT is barotrauma (pressure-related damage) to various susceptible parts of the body, including the inner ear, sinuses, teeth, and lungs. Heyboer et al. summarize the risks/side effects in Hyperbaric Oxygen Therapy: Side Effects Defined and Quantified, but the short version is that HBOT is quite safe, and serious complications are rare.

Minor barotrauma of the inner ear, which is the most common side effect, can usually be avoided by intentionally equalizing pressure in the ears by yawning, swallowing, etc during pressurization and depressurization.

Review of the Literature

Bekheit et al. Hyperbaric oxygen therapy stimulates colonic stem cells and induces mucosal healing in patients with refractory ulcerative colitis: a prospective case series. 2016. BMJ Open Gastroenterol.

This paper summarizes the clinical experience of physicians at the Faculty of Medicine, University of Alexandria in Egypt with using HBOT for refractory UC.
Between 1994 and 2011, 32 patients with refractory UC were treated with HBOT.
The total oxygen breathing time was 60 min with a 5 min air break at 30 min. The hyperbaric cycles were given at a pressure depth of 2.8 atmospheric absolute (ATA) (equivalent to 18 m). The sessions were repeated five times per week for eight consecutive weeks.
All patients received their medical therapy contemporaneously with the hyperbaric sessions.
All the patients (100%) included in the present study demonstrated a remarkably favorable clinical improvement, as well as improvement in both endoscopic and histopathologic parameters.
In our patients, we noticed that a pressure of 2.8 ATA was important for the therapy to be effective.
Conclusion: HBOT is effective in the setting of refractory UC. The described protocol is necessary for successful treatment. The mechanism of action of HBOT in treatment of refractory cases of UC involves stimulation of colonic stem cells to promote healing.

Buchman et al. Hyperbaric oxygen therapy for severe ulcerative colitis. 2001. J Clin Gastroenterol.

We describe the first successful use of hyperbaric oxygen therapy in the treatment of ulcerative colitis, refractory to conventional therapies.
Therapy consisted of 30 courses of 100% oxygen at a pressure of 2.0 atm absolute.
Clinical remission was achieved on the basis of the Truelove-Witts and disease activity index scores. Corticosteroids were successfully tapered off once remission was achieved.

Dulai et al. A phase 2B randomised trial of hyperbaric oxygen therapy for ulcerative colitis patients hospitalised for moderate to severe flares. 2020. Aliment Pharmacol Ther.

Treated 20 UC patients hospitalized for acute flares with hyperbaric oxygen (75% prior biologic failure)
Day 3 response was achieved in 55% (n = 11/20), with significant reductions in stool frequency, rectal bleeding and CRP (P < 0.01)
A more significant reduction in disease activity was observed with 5 days vs 3 days of hyperbaric oxygen (P = 0.03)
Infliximab or colectomy was required in only three patients (15%) despite a predicted probability of 80% for second-line therapy
Day 3 hyperbaric oxygen responders were less likely to require re-hospitalisation or colectomy by 3 months vs non-responders (0% vs 66%, P = 0.002)

Dulai et al. Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis patients hospitalized for moderate-severe flares: a phase 2A pilot multi-center, randomized, double-blind, sham-controlled trial. 2018. Am J Gastroenterol.

UC patients hospitalized for moderate-severe flares randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8)
A significantly higher proportion of HBOT-treated patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04)
HBOT-treated patients less often required progression to second-line therapy during the hospitalization (10 vs. 63%, p = 0.04)
The proportion requiring in-hospital colectomy specifically as second-line therapy for medically refractory UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07)

Dulai et al. Systematic review: the safety and efficacy of hyperbaric oxygen therapy for inflammatory bowel disease. 2014. Aliment Pharmacol Ther.

Fahad et al. Hyperbaric Oxygen Therapy Is Effective in the Treatment of Inflammatory and Fistulizing Pouch Complications. 2020. Clin Gastroenterol Hepatol.

Gürbüz et al. A different therapeutic approach in patients with severe ulcerative colitis: hyperbaric oxygen treatment. 2003. South Med J.

We present a case of clinical remission after HBOT in a patient with UC who did not respond to treatment with 5-amino salicylic acid, methylprednisolone, and azathioprine.

Hasan et al. Hyperbaric Oxygen Therapy in Chronic Inflammatory Conditions of the Pouch. 2021. Inflamm Bowel Dis.

Conclusions: Despite minor adverse events, HBOT was well tolerated in patients with CARP and significantly improved symptoms and endoscopic parameters.

Heyboer et al. Hyperbaric Oxygen Therapy: Side Effects Defined and Quantified. 2017. Adv Wound Care.

Pagoldh et al. Hyperbaric oxygen therapy does not improve the effects of standardized treatment in a severe attack of ulcerative colitis: a prospective randomized study. 2013. Scand J Gastroenterol.

Patients with severe attack of UC were randomized to HBOT (n=10) or control (n=8).
HBOT group received 30 total sessions at 2.4 ATM for 90min each over a span of 6 weeks
Both groups received standard treatment, including prednisone and mesalazine
Results: The authors found no statistically significant differences between the treatment groups in any of the assessed variables.

Singh et al. Hyperbaric oxygen therapy in inflammatory bowel disease: a systematic review and meta-analysis. 2021. Eur J Gastroenterol Hepatol.

Seven observational studies including 425 participants reported clinical response for ulcerative colitis. The pooled response rate of HBOT in ulcerative colitis was 83.24%
Three randomized studies with 118 participants were available for analysis.
Of the three published randomized trials, two studies showed no benefit of using adjunctive HBOT while one study showed short-term benefit in achieving clinical remission without using second-line therapy.
The study by Dulai et al., which showed benefit with the use of HBOT, was deemed to be methodologically sound with least risk of bias.
Two studies reported about the use of HBOT in the setting of medically refractory or complicated pouchitis and found improvement in modified Pouchitis Disease Activity Index

Thom, Stephen R. Hyperbaric oxygen – its mechanisms and efficacy. 2012. Plast Reconstr Surg.

Wu et al. The role of hyperbaric oxygen therapy in inflammatory bowel disease: a narrative review. 2021. Med Gas Res.

Clinical and experimental studies have revealed that HBOT may exert its therapeutic effect by inhibiting inflammation and strengthening the antioxidant system, promoting the differentiation of colonic stem cells and recruiting cells involved in repair.