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Hyperbaric Oxygen Therapy for Ulcerative Colitis

Alyssa Luck · Mar 14, 2022 · Leave a Comment

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. 

Animal Studies

Akin et al. Hyperbaric oxygen improves healing in experimental rat colitis. 2002. Undersea Hyperb Med.

Atug et al. Hyperbaric oxygen therapy is as effective as dexamethasone in the treatment of TNBS-E-induced experimental colitis. 2008. Dig Dis Sci.

Gorgulu et al. Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid-induced colitis in rats. 2006. Dig Dis Sci.

Gulec et al. Effect of hyperbaric oxygen on experimental acute distal colitis. 2004. Physiol Res.

Parra et al. Hyperbaric oxygen therapy ameliorates TNBS-induced acute distal colitis in rats. 2015. Med Gas Res.

Rachmilewitz et al. Hyperbaric oxygen: a novel modality to ameliorate experimental colitis. 1998. Gut.

Related

Inflammatory Bowel Disease Crohn's disease, HBOT, hyperbaric oxygen therapy, IBD, ulcerative colitis, wound healing

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Hi! I’m Alyssa. This website is where I house all of my musings and investigations and pet research projects – topics ranging from autoimmune disease to nutrition to adult palate expansion to psychology and nervous system therapy. I hope you enjoy this awkwardly cropped poor resolution photo of me playing mini golf. If you want to know more about me, click here!

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Photo dump from the last year. Thanks to everyone Photo dump from the last year. Thanks to everyone who made 28 the best yet - excited for 29🥰

(PS. In case anyone wants to know what it’s like in my head, I was going to write something like “year 28” or “my 28th year” but then I realized that the year between your 28th and 29th birthdays is not your 28th year of life, it’s your 29th year. I am turning 29 because I have been alive for 29 years. So then I had a whole thing about how to word it without being inaccurate and ended up going with what you see above which is vague and weird but the point is it was a good year and I love all the people in my life dearly)
Biology of Belief (2005) was written by Bruce Lipt Biology of Belief (2005) was written by Bruce Lipton, who earned a PhD in developmental biology in 1971 and was an anatomy professor and academic researcher in the 70s and 80s. Despite the book's presentation and Lipton's background, this is not a science book. It is an exposition of an ideology, supported by haphazard and poorly contextualized nuggets of evidence, rhetorical leaps, and a mind-boggling overuse of analogies. 

The book largely failed to deliver on its promised content. What it does is argue for the primacy of the environment over DNA in controlling life; propose that the cell membrane rather than the nucleus is the "brain" of the cell; invoke quantum physics to explain why modern medicine fails; explain that our behavior is largely controlled by our subconscious mind; inform parents that they therefore have a great deal of control over the destiny of their children; and conclude that humans must become nonviolent protectors of the environment and of humanity because Everything Is Connected.

It’s not that these points aren’t relevant to the topic at hand - they are. But they were not connected in a coherent way that would explain how “belief” actually works (like…biologically), and the treatment of scientific concepts throughout was careless, or perhaps disingenuous.

I think he's correct about many things, some of them being common knowledge. For instance, the "new" science of epigenetics is now old news, as is the critical role of parenting and early environment in shaping a child’s future. But however important these and attendant concepts may be, the book did not do a good job explaining, supporting, or connecting them. 

As far as practical guidance, he refers the reader to a list of resources on his website, which is fine, but I expected some scientific insight into how/why those modalities work. None was given. 

On the plus side, the book was quite thought-provoking, and I came away with loads of references and topics to follow up on. My favorite line? "There cannot be exceptions to a theory; exceptions simply mean that a theory is not fully correct."
Friedrich Nietzsche, The Gay Science (section 382) Friedrich Nietzsche, The Gay Science (section 382), as quoted in the introduction to Thus Spoke Zarathustra because I like the translation better.
This paper totally changed the way I think about e This paper totally changed the way I think about early nervous system development and the relationship between physiology and sociality. 

The authors propose that newborn babies are not inherently social, and have just one goal in life: physiological homeostasis. I.e. staying alive. This means nutrients, warmth, and regulation of breath and heart rate, i.e. autonomic arousal (it’s well-accepted that newborns sync their breathing and heart rate with caregivers through skin to skin contact). 

All these things are traditionally provided by a loving caregiver. So what the baby experiences during the first weeks of life, over and over, is a shift from physiological perturbation to homeostasis (a highly rewarding event inherently) REPEATEDLY PAIRED with things like the sound of a caregiver’s voice and seeing their face. Thus, over time, the face/voice stimuli become rewarding as well. 

The authors argue that THIS is the beginning of humans’ wiring for sociality, and may explain why loving social interactions can have such a profound regulating effect on physiology throughout life: because the brain was trained for it at an early age. 

This framework holds all kinds of fascinating implications for what happens if that initial “training” isn’t so ideal. What if the return to nutritional homeostasis via feeding is paired with negative expressions and vocalizations rather than loving ones, perhaps as could occur with PPD? What happens if the caregiver has poor autonomic regulation, such that social stimuli become paired with cardiorespiratory overexcitement in the baby? Could that have potential for influencing later introversion vs extroversion? (Because if social interaction is paired with autonomic overexcitement, that could lead to social interaction literally being more energetically draining, which is what introverts experience. Thoughts?)

For my energy metabolism enthusiasts: Table 1 in the paper draws a link between metabolic rate and sociality across species. Swipe for a screenshot. 

Anyway, check out the paper! It’s free, just google “growing a social brain pdf.”
I’ll be under general anesthesia in a couple day I’ll be under general anesthesia in a couple days to have two tooth implants placed, and I think I’ll take the opportunity to have a little heart-to-heart with my subconscious mind. A bit of medically-assisted self-hypnosis, if you will. 

I randomly stumbled upon these papers a couple months ago - an RCT showing reduced post-op pain in patients who listened to recorded positive messages while under general anesthesia, plus a post-hoc analysis of the same data that found reduced post-op nausea and vomiting in a subset of high-risk patients. 

The full review paper from the first slide is unfortunately in German, but it has long been recognized that even when unconscious, the patient is listening (for better or for worse). 

It boggles my mind that it isn’t standard of care to have patients listen to recordings like this while under sedation, considering that almost nothing could be easier, safer, or cheaper, and we have at least some evidence of significant efficacy. I mean c’mon, what more could you want from an intervention? 

(Yeah, I know. Profit. If anyone still thinks that our medical system operates with patient well-being as the foremost goal, you’re deluding yourself.)

“There should be a fundamental change in the way patients are treated in the operating room and intensive care unit, and background noise and careless conversations should be eliminated.”

“Perhaps it is now time to finally heed this call and to use communication with unconscious patients that goes beyond the most necessary announcement of interventions and is therapeutically effective through positive suggestions. When in doubt, assume that the patient is listening.”
If you've seen "vagus nerve exercises" that have y If you've seen "vagus nerve exercises" that have you moving your eyes or tilting your head, you've probably encountered the work of Stanley Rosenberg. The exercises he created and introduced in his 2017 book now appear in instructional videos all over the internet. 
 
The book itself has much to recommend it: it's accessible, it's practical, it's inspiring. But it has one major flaw: the solid practical and informational content regarding the cranial nerves is framed in terms of the scientifically dubious polyvagal theory. 
 
I particularly enjoyed the book as an introduction to the therapeutic arena of bodywork, of which Rosenberg is a skilled practitioner. His book is full of case reports that demonstrate how immensely powerful extremely subtle movements and physical manipulations can be. These do need to be kept in perspective: it's a small sample size of the most remarkable cases, and the results were achieved within the supportive clinical environment of a skilled practitioner. You can tell from his descriptions how refined his technique is. But nevertheless, it was a paradigm-shifting read for me, and the exercises give you something concrete to play around with. 
 
The book also brought the cranial nerves and the concept of “social engagement” to the fore as arbiters of health. Rosenberg has a solid background in cranial nerve anatomy and shares many interesting tidbits and considerations that you don’t typically hear; for instance, the potential impact of dental and orthodontic work on cranial nerve function.
 
So, is it worth reading? If any of the above piques your interest, go for it! Just read my post on polyvagal theory first – you can use the book to practice separating the wheat (solid informational content) from the chaff (pseudoscientific framing). If nothing else, the book is a nice reminder that genuine healers who get lasting results for their patients do exist.

But if you just want to try the exercises, you can easily find them all on YouTube. 

“You learn techniques to understand principles. When you understand the principles, you will create your own techniques.” -Stanley Rosenberg
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