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Hyperbaric oxygen therapy seems like an obvious choice for energy-depleted people with ME/CFS, long COVID, and fibromyalgia… But can it deliver the goods?

If oxygen provides the stuff of energy and people with ME/CFS, FM and long COVID are energy depleted...How could HBOT not help? (Image by ChristineLMiller - Wikimedia Commons).

If oxygen provides the stuff of energy …  and people with ME/CFS, FM and long COVID are energy depleted … how could HBOT not help? (Image by ChristineLMiller – Wikimedia Commons).

It seems so obvious. How could delivering massive amounts of oxygen to energy-depleted, oxygen-deprived long COVID, chronic fatigue syndrome (ME/CFS), and fibromyalgia (FM) patients not work?

Hyperbaric oxygen therapy (HBOT) potentially promises much. Studies suggest it may be able to increase the amount of oxygen being delivered to the brain, in particular, thus potentially improving metabolism, microglial cell functioning, and blood vessel functioning, promoting blood/brain integrity, reducing inflammation, and inducing neuroplasticity. Some researchers believe the ability of HBOT to revive dysfunctional brain regions (i.e., increase neuroplasticity) may be its greatest strength.

Of course, there’s also the potential impact on the mitochondria as well as HBOT’s possible ability to regenerate muscle fibers and increase muscle strength. Plus, the combination of delivering high oxygen levels in combination with hyperbaric pressure appears to trigger the activation of “regenerative processes” including stem cell proliferation and the induction of anti-inflammatory factors.

All that makes HBOT an intriguing option given the hypometabolism found in the brains of ME/CFS/FM and long-COVID patients and the low oxygen uptake David Systrom’s invasive exercise tests have consistently found in a subset of ME/CFS patients.

On the other hand, HBOT’s ability to shove oxygen seems like a blunt force kind of option that might temporarily help but not necessarily repair the problem. One would not think it would fix a shunt that’s moving blood past the muscles, nor a mitochondrial problem.

However, if ME/CFS/FM and long COVID are caused by systems that get stuck in some kind of hypoxic, inflammatory positive feedback loop (aka Martin Pall’s NO/ONOO hypothesis), then clearing up that toxic state might do the trick and flip the system back to normal. For instance, by repeatedly reducing inflammation, HBOT sessions might be able to calm the microglial cells down enough that they stop being so reactive.

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Check out what we’ve learned about the efficacy of HBOT in long COVID, ME/CFS, and fibromyalgia.

Long COVID

Case Report: An Israeli case report provided an encouraging picture. Three months after a coronavirus infection had landed him in the hospital for a short stay, a formerly healthy and athletic 55-year-old was experiencing shortness of breath with exercise and cognitive problems. An MRI revealed that problems with small blood vessels in his brain were present – and apparently preventing his brain from getting the energy it needed.

He was given 60 x 90-minute sessions, 5 days per week at 2 atmospheres pressure. His improvement was rapid. After the first five sessions, he reported that his breathing was better and his muscle aches after exercise were gone. After 15 sessions, he noted less fatigue and an improvement in his previous low energy. After 20 sessions, he noticed that his breathing and ability to exercise had returned to normal and he was back to running mountain trails! His cognitive problems were gone as well.

Notice the diminishing red in the white images - indicating less hypometabolism - and the increased red in the B row - indicating increased oxygenation in this ME/CFS case report.

Notice the diminishing red in the white images in the C row, indicating less hypometabolism as well as the increased red in the B row, indicating increased oxygenation.

MRIs indicated that blood flows to the brain had increased. Cognitive testing validated the man’s experience when it showed he’d experienced significant improvements in global memory, executive functioning, attention, information processing speed, cognitive flexibility and multitasking.

A maximal cardiopulmonary exercise test continued the good news with a 34% increase in the VO2 max (energy production), a 34.4% improvement in the maximal METs, and a 16.9% increase in the lactic threshold. Lung functioning was improved by 44.3%, and lung perfusion by 20.2%.

It was all very good. Of course, it was possible that he might have improved on his own, but his rapid return to health upon starting HBOT suggested it was the cause.

Randomized Trial – The Israelis – who loom very big in this field – produced a bigger, more rigorous study in Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. This time, 73 long-COVID participants were divided up into HBOT (n=37) and sham HBOT (n=36) groups and given 40 sessions at 2 atmospheres pressure (five sessions a week over a two-month period). The sessions were 90 minutes, with five-minute air breaks every 20 minutes. Various symptom questionnaires including the SF-36 functional assessment questionnaire were given.

The trial required only that the long-COVID patients experience cognitive problems that affected their quality of life. With almost a quarter of the long-COVID patients (23%) not experiencing fatigue, and with over 60% of the group still working full-time, it was clear that a substantial subset would not have met the criteria for ME/CFS.

Both the sham and HBOT groups improved cognitively, but executive functioning and attention – two key areas in ME/CFS – improved only in the HBOT group. The authors proposed the increased blood flows to the frontal cortex of the brain was responsible.

Interestingly, microstructural improvements were found in the same area of the brain as in fibromyalgia patients who’d experienced childhood abuse. As in that fibromyalgia study, HBOT reduced symptoms of depression as well as pain and fatigue.

The physical functioning portion of the SF-36 asks how limited a person is over a range of activities – from running, to climbing several flights of stairs, to one flight of stairs, to bathing and dressing oneself – that a person experiences. They were fairly limited (60/100), but HBOT didn’t make much of a difference. People who weren’t able to climb several flights of stairs before HBOT apparently weren’t able to afterward.

The physical limitations portion, however, provided a very different picture. It asks how about your limitations regarding daily life activities such as work.

“During the past 4 weeks, have you had any of the following problems (cut down work; accomplished less, limited in the kind of work, difficulty performing work)…. as a result of your physical health?”

The participants’ initial scores (17/100) in the physical limitations questionnaire indicated that they’d had to dramatically cut down their daily activities.

HBOT didn’t remove all their limitations, but it did improve them significantly (from 17 to 51). Similarly, HBOT increased their energy scores (28-46) significantly (but not nearly to optimal health), and improved the extent to which pain interfered with their functioning (39-60).

The UK Trial – The title of a recent UK trial, “Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention“, fairly bursts with enthusiasm. This trial, done at a long-COVID clinic, was shorter – just 10 x 105-minute sessions (3 x 30-minute exposures to 100% oxygen) at 2.4 atmospheres pressure over 12 days. In the introduction, the authors noted, “in particular, HBOT has been shown to be safe and effective in the treatment of chronic fatigue syndrome.”

Instead of a mask, this study used the Midlands Diving Chamber and assessed effectiveness with the Chalder fatigue scale and a cognitive test called the NeuroTrax evaluation.

Even though the trial was small, the authors reported that the effect sizes were large – “suggesting that a substantial improvement had occurred.” Indeed, they stated that the change in the Chalder fatigue scale, information processing speed, and attention were “very large”, and global cognition, executive functioning, and verbal functioning were “large”.

Conclusion: The two HBOT long-COVID studies and the case reports all produced good results with recently ill patients. Encouragingly, even a short trial (10 sessions) produced, according to the authors, large effect sizes – suggesting that the trial produced real-life results.

Fibromyalgia

With HBOT studies stretching back 15 years, fibromyalgia easily leads the pack in HBOT studies. Way back in 2004, a Turkish study concluded that “HBO therapy has an important role in managing FMS”. It wasn’t till about 2015, though, that the FM HBOT studies really got rolling.

A Canadian group doing a metareview of chronic pain studies (including fibromyalgia) concluded:

“Early clinical research indicates HBOT may also be useful in modulating human pain; however, further studies are required to determine whether HBOT is a safe and efficacious treatment modality for chronic pain conditions.”

2016 brought the first largish, Israeli FM study. It included 60 women who received 40 sessions of 100% oxygen for 5 days/week for 90 minutes at 2 atmospheres of pressure. The goal of the study, as in most other studies, was to enhance neuroplasticity in order to tamp down the activity of the pain-enhancing brain circuits and boost the activity of pain-inhibiting circuits.

The study did just that: it decreased the hyperactivity of some regions (insula, anterior cingulate cortex, prefrontal cortex, thalamus), while increasing the activity of others. It also improved sleep, cognitive functioning, increased energy, and improved general well-being.

Activity increases and reductions after HBOT in fibromyalgia

Note that highest activity increases (red) were in the prefrontal cortex while the highest activity reductions (blue) were elsewhere. (From the study)

HBOT’s impact on immune functioning was assessed in a 2016 study that included 40 90-minute sessions for 5 days/week at 2 atmospheres of pressure. The study found a “dramatic modification” of the pro-inflammatory status of FM patients but symptom severity, alas, was not dramatically affected with only pain perception showing a significant decrease.

The Gist

  • Hydrogen oxygen therapy appears to promise much for energy-depleted, oxygen-deprived people with ME/CFS and long COVID.  Its possibilities include taming neuroinflammation, enriching neuroplasticity, improving cognition, increasing energy, improving muscle function, etc. 
  • It seems like it’s made to order, but it also seems like a blunt instrument. If blood is being shunted away from the muscles, or if the mitochondria are damaged, it’s not clear how much providing extra oxygen will help. On the other hand, if an oxygen-deprived, inflammatory environment is feeding on itself, then fixing that environment could allow the system to reset itself and return to health. 
  • The few long-COVID HBOT case reports/studies have been small but positive, and suggest that in the right person, HBOT may even help return a person with long COVID to health. 
  • More fibromyalgia HBOT studies have been done than in long COVID or ME/CFS and their results – dating back over ten years – are decidedly mixed.  Some studies have found little to no symptom improvements, others have found moderate improvements, and a few have found significant improvements.
  • Several FM and long-COVID studies/case reports have found, though, that HBOT has been able to reverse brain abnormalities and enhance the functioning parts of the brain that have been inhibited (such as the prefrontal cortex), and also tamp down parts of the brain that have been overactivated.
  • Few ME/CFS studies have been done, and the results have ranged from moderate to good.
  • While case reports do indicate that progress can occur rapidly, in general, it seemed that more sessions (>20) worked better than fewer sessions (20 or less).
  • While recoveries have been published, HBOT appears to be less of a game-changer for most than a moderate help. 
  • Much remains to be learned, however. We need large, placebo-controlled trials that can provide information on the optimum doses, what kinds of patients are helped, how they are helped and how long the help lasts. Unfortunately, according to clinicaltrials.gov, none of these trials appear to be underway at present.
  • A recent gift of two hyperbaric oxygen chambers to Nancy Klimas’s Institute for Neuro-Immune Medicine at Nova Southeastern University in southern Florida provides the potential, though (once the infrastructure to support them has been built out) for us to learn much about the effectiveness of HBOT in ME/CFS/FM, GWI, and long COVID.
  • If you’ve tried HBOT, please tell us how it went in the poll towards the bottom of the page. 
A 2019 Italian HBOT study demonstrated a) that more is probably better, and b) how misleading findings of “statistically significant improvements” can be. The trial, which consisted of three days of 90 minutes HBOT per week for a total of 20 sessions at 2.5 atmospheres of pressure, was shorter than some others and it may have shown.

The authors noted, “All of the scales in the physical component of the SF-36 significantly improved after 20 sessions (but not after 10)”. There’s nothing wrong with a 30% increase in a score, for sure, (general health status (26-35), bodily pain (21-30), and physical functioning (41-48)), but the patients hardly returned to health, either.

Another short but intriguing Italian study found that 20 sessions of HBOT at 2.4 atmospheres of pressure did not improve muscle strength or change muscle fibre content but did improve the ability of the central motor cortex to more efficiently recruit muscle fibers during exercise – potentially a very helpful thing. Yet another Italian study did not find improvement in symptoms, quality of life, or interstitial cystitis factors in FM patients with interstitial cystitis after 40 90-minute sessions of HBOT over 5 weeks at 2 atmospheres of pressure in a chamber.

A Spanish 40 sessions x 90-minute HBOT study at 1.45 atmospheres of pressure found HBOT did not improve oxygen saturation or heart rate during a six-minute walk test. The authors reported that HBOT did ‘significantly” increase the distance walked, but again, this may be misleading as the HBOT group increased from 481 to 513 meters (while the graduated exercise group increased from 508 to 558 meters). A 9% increase is apparently considered “clinically significant”, but one wonders how impressive the result was to the participants. Despite the larger number of HBOT sessions used, this study’s results were not impressive. Note, however, the significantly lower pressure used (1.45 ATA compared to 2-2.5) used in this study.

Another 40 session, 5 days per week, HBOT study at 2.0 ATA, this time in Toronto, involved 18 patients. This time the results were better, with the authors reporting that HBOT improved global functioning, reduced symptoms of anxiety and depression, and improved the quality of sleep. Notably, for the first time, a long-term follow-up assessment was done which indicated that the improvements were sustained at 3 months.

Conclusion: the results were mixed, with two studies providing moderate results, four reporting little or no symptom improvement, and two reported significant symptom improvement. The low atmospheric pressures in one study may have blunted its results. Another short study, though, did not benefit from higher pressures.

Chronic Fatigue Syndrome (ME/CFS)

A 31-year-old man, with a 1 1/2-year case of ME/CFS triggered by infectious mononucleosis that produced weakness, memory complaints, dizziness, and muscle/joint pains, received 50 sessions of HBOT over 6 weeks. (No other HBOT measures given.)

Brain PET Scans were done before and after the HBOT. The first scan generally validated what other studies have found: the man demonstrated widespread hypometabolism in the frontal cortex, and in the posterior cortical regions (precuneus, parietal, temporal, and occipital), and amygdala-hippocampal complexes, and cerebellum, which was largely reversed after HBOT.

This man’s physical and mental functioning scores of the SF36 increased by about 20 and 40 percent (from 57-70; 48-69) after HBOT. He was clearly still not well, but he experienced significant improvement in physical functioning and dramatic improvement in mental functioning.

A small (n=10) 2013 Turkish study provided 15 treatment sessions of HBOT therapy for five days over a 3-week period. It used the Visual Analog Fatigue Scale (VAFS), Fatigue Severity Scale (FSS) and Fatigue Quality of Life Score (FQLS) scaled. The HBOT therapy was well tolerated and the authors reported that the patient scores for fatigue, fatigue severity and fatigue quality of life all dramatically improved.

ME Research UK reported that in 2006, Action for ME’s survey found that some people with ME/CFS reported HBOT helped with brain fog or concentration, but others reported no lasting improvement.

Conclusions

It’s hard to draw a conclusion from these studies. The many different symptom assessment tools used and the lack of clarity about how clinically significant some “statistically significant” results are made it difficult to assess how effective many of these studies were.

The long-COVID and ME/CFS patient report suggested that HBOT can be very effective in the right patient and the long-COVID trials appeared to produce the best results. The fibromyalgia trials were not as successful, with some reporting significant benefits but others reporting few improvements in symptoms. Still, several studies showed that HBOT was able to improve brain functioning.

While one person with long COVID quickly returned to normal functioning, it appeared the studies that did more HBOT sessions had better results.

In general, it appears that when HBOT works, it’s usually less a game-changer than a moderate improver of symptoms. There is much, though, that we don’t know. We don’t know which patients HBOT works best in, nor how long the effects last. It was encouraging to see one study find the positive effects were still present 3 months later.

We clearly need large, rigorously controlled studies that have the ability not just to determine if HBOT works in long COVID, fibromyalgia, and ME/CFS but in which individuals it works, the optimum dose (length and number of sessions, atmospheric pressure) to use, how it does what it does, and most importantly, how long the effects last.

Indeed, the small (and enthusiastic) UK trial asserted, “there is an urgent need for larger-scale randomized placebo-controlled trials” as well as a registry of patients receiving HBOT for long COVID. (Both are now developed at the University Hospitals Coventry and Warwickshire NHS Trust and the Midland Chamber.)

The HBOT Poll for FM, ME/CFS, and Long COVID

If you’ve tried HBOT, please tell us how it went:

The Future

Few major HBOT studies, however, appear to be underway in ME/CFS, FM or long COVID.  An 80-person, randomized, placebo-controlled, long-COVID Swedish study that will also investigate endothelial functioning is underway, but the study will include only 10 sessions, and those ten sessions will take place over six weeks (!) making it easily the least intensive study of any yet undertaken.

Clinicaltrials.com lists one other fibromyalgia HBOT study – a randomized but not placebo-controlled 60-session Israeli trial. No chronic fatigue syndrome trials are underwa,y but there is some exciting news from the ME/CFS front: a major ME/CFS treatment and research center has received two HBOT chambers.

The Lozick Family Foundation has donated two hyperbaric chambers to Nancy Klimas’s Institute for Neuro-Immune Medicine at Nova Southeastern University in southern Florida. Not only do these chambers provide the opportunity to get HBOT treatment in a safe environment but in a research environment as well. Dr. Klimas’s use of the chamber could tell us much about the effectiveness of this treatment option in ME/CFS, GWI, long COVID, and others.

First, the Institute needs, though, to build out the infrastructure to support the chambers before it can start using them.

Moderate improvement is nothing to sneeze at. Personally, I think it’s a lot to ask of any treatment that it be “it” for a disease like long COVID or ME/CFS. I would also bet that we won’t know the true value of HBOT until it’s used with other therapies that complement it. How about HBOT with anticoagulants? Or HBOT with mitochondrial enhancers, or antioxidants and anti-inflammatories to cool the flames down? My guess is that innovative doctors like Nancy Klimas that combine HBOT with other therapies will give us our best understanding of its value.

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This was a long blog, but HBOT is serious stuff now and a long blog is what it took to give its due.

Neither I nor Health Rising’s guest bloggers take the short view. We don’t rely on abstracts, for instance, but try and read the studies and puzzle these things out ourselves. That’s why, at times, we may question whether a result – even a statistically significant result – really means anything.

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