Long-term daily mHBOT and full recoveries w/ ongoing maintenance

Jenny

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Would you know if you are a viral ME/CFS patient, or if you are a Lyme disease ME/CFS patient?

My presumption is that theoretically, HBOT may work better for Borrelia than viruses.

No idea. I was diagnosed with borrelia at the Breakspear many years ago and had years of abx which did nothing. I don't have any confidence in that diagnosis. Also had years of Valtrex which did nothing.
 

Jenny

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@Jenny,

did/do you have any pain symptoms? Did it help them? If so what were they etc.

Yes I have had a lot of pain over the years, particularly back of neck, shoulders, mid back, knees and hands. Also bad headaches. I've had no pain since HBOT but the pain always fluctuated a lot, more than other symptoms, so difficult to say definitively that it helped.
 

rodgergrummidge

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I have been looking over the HBOT discussions. Overall, it seems that HBOT might provide modest improvements, but only after many many sessions, sometimes lasting several months and only in some patients.

HBOT treatments can clearly be effective in the treatment of decompression sickness, CO poisoning, and severe ischaemia associated with trauma or infection. 'Off-label' uses of HBOT may also be useful in individuals that have low arterial hemoglobin O2 saturation. Low arterial hemoglobin O2 saturation can be caused by lung diseases that decrease O2 delivery to Hemoglobin in the blood. Low arterial hemoglovin O2 saturation can also be caused by mutations in hemoblobin. In such cases, HBOT might be an effective treatment because it can increase the delivery of O2 to hemoglobin in the lungs and so decrease tissue ischaemia and improve symptoms.

Info from HBOT clinics most often claim that it increases O2 delivery to tissues because it increases O2 dissolved in bodily fluids. For example, one clinic claims that "oxygen is dissolved into all of the body's fluids, the plasma, the central nervous system fluids, the lymph, and the bone and can be carried to areas where circulation is diminished or blocked. In this way, extra oxygen can reach all of the damaged tissues and the body can support its own healing process."

This type of mechanism is central to the claims of many HBOT clinics and has also been suggested in this thread by others.
and gets more oxygen into my system.

But, such a mechanism doesnt make much biological sense. As shown in the fig below, when a patient is provided with 100% O2 concentration (ie with HBOT), the amount of O2 dissolved in body fluids is <1% of the total O2 bound to hemoglobin. So, if the arterial oxygen saturation of hemoglobin is normal, delivering extra oxygen to "dissolve into all the body's fluids, the plasma and the central nervous system fluids" would have essentially no major effect.
upload_2018-1-2_3-43-56.png


some is carried in the interstitial fluid round the cells, but is considered insignificant so is ignored. Dr James' reasoning was that this oxygen becomes important when the small blood vessels are damaged so haemoglobin can't reach where oxygen is needed but the fluid still bathes the area. The HbOT increases the amount of oxygen in the fluid so that it is available in these damaged areas.
I'm not sure who Dr James is, but he seems to misunderstand the levels of O2 carried by hemoglobin compared to the amounts dissolved in blood and other fluids (as outlined in the graph above). The O2 in interstitial fluid is very low, less than 1% at 100% ATM O2. HBOT doesnt appear to provide clinically significant O2 concentrations dissolved in blood and tissues. In fact, HBOT treatment is not provided clinically to patients with conditions where arterial hemoglobin O2 saturation is normal but have decreased O2 delivery to tissues (eg. due to damaged vessels, poor perfusion or ischaemic injury).

Given that HBOT responses in CFS patients mostly occurs after many many dives over several months (some random selected quotes below), I wonder whether the improvements are really due to HBOT and not some other factors. The efficacy of HBOT treatment seems low. It concerns me that HBOT clinics are telling patients that they may need over 50 dives or more than 6 months of expensive HBOT treatment that has low efficacy. It also seems strange that HBOT treatment is recommended in some HBOT clinics without firstly performing basic (and cheap!) path tests to determine whether arterial and venous O2 saturation of hemoglobin are abnormal.

Hi Misfit Toy et all,
I have been taking HBOT(oxygen treatment) since June...20 intensive treatments(close together) then once weekly.In my case so far, I haven't felt any significant improvement.

The key difference from the HBOT reports I've read on PR and the ones on this thread are frequency and quantity of use. Some of these patients went a full year every day before seeing significant improvement.

I've had full remission from HBOT. I had done 80 dives using the professional, hard shell chambers. It was not until dive ~75 did I get full remission. I noticed benefits right away in the first 10, then sort of slowely improved or plateaued for a while,

I continued for 2 months, usually 5 days a week. At the end I was slightly better in terms of energy. But it was a very hard job to do 5 times a week. I was planning to do at least 80 or 100 sessions, because some people report late responses.

I also had some moderate improvement in brain fog, so in general it felt like going to a better direction. But I can't say 41 sessions led to an important improvement.

I know one ME/CFS patient on this forum who was taking regular twice weekly HBOT sessions for free at their local multiple sclerosis hyperbaric chamber, and they said that it helped with the tiredness, but no major improvements

From PR member @Theodore on another thread. 50 sessions of hbot greatly improved his pain symptoms, helped with fatigue, and normalized his SPECT / PET scans

I think @Murph summarizes some of these HBOT concerns perfectly below:
However, somewhere between the long time frames taken to achieve remission, the high prices and the lack of plausible mechanism for it to work, my normal willingness to draw evidence from patient reports ebbs with this particular treatment.

The oxygen uptake by muscles of Fukuda patients is very low (about 44% that of the worst functioning controls).
Seems there are plausible mechanisms by which HBOT can help.
It is true that some CFS patients have reduced delivery of O2 to tissues including muscles. If this was due to a lung problem that caused reduced hemoglobin O2 saturation, HBOT would be a great treatment. However, this is not the case for most CFS patients. Many CFS patients have normal arterial O2 hemoglobin saturation but reduced delivery (or utilization?) of O2 to muscles and other tissues. According to the graph above, trying to deliver an extra <1% O2 that is dissolved in blood and tissues using HBOT seems an expensive approach with a low likelihood of efficacy.

Given these issues, how is HBOT supposed to work in CFS patients?

Rodger
 

Hip

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HBOT doesnt appear to provide clinically significant O2 concentrations dissolved in blood and tissues.

HBOT does in fact provide large increases in the amount dissolved oxygen in the blood: with a HBOT dive at 3 atmospheres and breathing pure oxygen, the amount of dissolved oxygen in the blood increases by 20 times, going up from the normal 0.3 ml/dl to 6 ml/dl. See this paper:
At sea level the blood oxygen concentration is 0.3 ml/dl. Tissue at rest draw 5 to 6 ml of oxygen per deciliter of blood assuming normal perfusion. Administering 100% oxygen at normobaric pressure increases the amount of oxygen dissolved in the blood to 1.5 ml/dl (five folds) and at 3 ATA the dissolved oxygen content is approximately 6 ml/dl, much more than the resting cellular requirement.

Although not all HBOT dives use pressures as high as 3 atmospheres.

HBOT will not change the amount of oxygen bound to hemoglobin very much, because hemoglobin is normally nearly 100% saturated with oxygen anyway. But HBOT does increase the amount of oxygen dissolved in the blood by a substantial amount.


I can't think of any theoretical reason why that 20-fold increase in dissolved oxygen would have much affect against viruses in ME/CFS, but theoretically it might help kill anaerobic bacteria, for which oxygen is poisonous. Lyme is nearly anaerobic, so in principle HBOT might work for Lyme. I'd like to see a study conducted on HBOT for chronic Lyme disease.


The amount of oxygen that dissolves in the blood is proportional to the air pressure in the lungs, and also proportional to the percentage oxygen concentration in the air. So if you change the oxygen concentration from its normal 21% up to 100%, even at normal atmospheric pressure you get nearly 5 times more oxygen dissolved in the blood.


Something I cannot understand is why home soft (aka: mild) hyperbaric chambers, which typically operate at only 1.3 ATM, can offer any benefits over just breathing pure 100% at normal pressure. I tried to address this question in this post.
 

Jenny

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[QUOTE="rodgergrummidge, post: 945160, member: 313

It concerns me that HBOT clinics are telling patients that they may need over 50 dives or more than 6 months of expensive HBOT treatment that has low efficacy. It also seems strange that HBOT treatment is recommended in some HBOT clinics without firstly performing basic (and cheap!) path tests to determine whether arterial and venous O2 saturation of hemoglobin are abnormal.

Rodger[/QUOTE]

The thing is, in the two UK HBOT centres I've been to, there are no doctors on the premises on a day to day basis and no equipment with which to measure O2 saturation. And no one recommends any length of treatment. After a few trial sessions it seems to be up to the individual to tell the staff what level they want to go to and how often. Reviews are infrequent and cursory - just a checklist of symptoms.

Also treatment in MS centres is usually pretty cheap - I only pay £17 a session. They don't seem to be out to make lots of money.
 
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Jesse2233

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@rodgergrummidge take a look at these studies and let me know what you think

There seem to be mechanisms at play beyond hemoglobin saturation.
  • Mitochondrial function (1) (2)
  • Blood flow to the brain and other organs (3) (4)
  • Healing neurological damage (5) (6)
  • Anti-viral and anti-bacterial effects (7) (8)
  • Autoimmunity (9) (10)
  • Studies on the use of HBOT for fibromyalgia, CFS/ME, and Lyme (11) (12) (13) (14)
I'm aware these studies are imperfect in their sample size / methodology / etc but given funding levels it's the best we have
 
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rodgergrummidge

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HBOT does in fact provide large increases in the amount dissolved oxygen in the blood: with a HBOT dive at 3 atmospheres and breathing pure oxygen, the amount of dissolved oxygen in the blood increases by 20 times, going up from the normal 0.3 ml/dl to 6 ml/dl. See this paper:
@Hip the quoted info you pasted comes from Reference 1 of the paper you hyperlinked which is a 1953 publication (J Appl PhysioI1953;5:471-86) that is essentially wrong. The authors calculate O2 concentrations in the air and in the blood which, for a variety technical reasons, is inaccurate. The rate of diffusion of an individual gas should be determined by the relevant gradient of its partial pressure, rather than by its concentration. Thus, in the case of O2, it would be the partial pressure of O2 (pO2).

The graph I have repasted below shows that for a normal individual at sea level with >90% hemoglobin saturation, the amount of dissolved O2 is <1% of of the total O2 in the blood.

The graph also shows that for a normal individual, 1L of blood is able to carry ~200ml of O2 bound to hemoglobin (ie. 1/5 the blood volume is O2. remarkable!!) and ~2ml of dissolved O2. It also shows that for large increases in pO2, only very small increases in dissolved O2 are achieved. Thus, a 5-fold increase in pO2 concentration (going from 20% O2 to 100% O2 using HBOT) does not necessarily lead to a 5-fold increase either i) hemoglobin-bound O2 or ii) dissolved O2.
upload_2018-1-2_9-54-43.png

The graph shows for individuals with >90% arterial hemoglobin O2 saturation (which seems to be the majority of CFS patients), the amount of dissolved pO2 achieved using 100% O2 HBOT is extremely modest compared to the total amount of O2 carried by hemoglobin.

In fact, O2 sensors in the body detect very high pO2s and trigger feedback mechanisms to reduce O2 back to normal levels. In this way, 100% O2 can paradoxically reduce oxygen delivery to peripheral tissues by inducing a number of physiological effects such as vasoconstriction and reduction in cardiac output.

@Hip do you know of any more recent publications where clinically significant concentrations of dissolved O2 are achieved using HBOT (in individuals with normal saturated hemoglobin)? What pO2s are achieved?

Rodger
 

Hip

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The rate of diffusion of an individual gas should be determined by the relevant gradient of its partial pressure, rather than by its concentration. Thus, in the case of O2, it would be the partial pressure of O2 (pO2).

Certainly. Henry's law states that the amount of gas dissolved in a liquid is proportional to the partial pressure of that gas.

The partial pressure of oxygen in the air is given by its percentage concentration in the air (which is normally 21%) multiplied by the air pressure. So if you increase the air pressure, or you increase the oxygen concentration in the air, you will increase the oxygen partial pressure, and in turn dissolve more oxygen into the blood.

When I made my first rather naive Henry's law calculations (see this post) on how much more oxygen would dissolve into the blood during HBOT, I calculated that breathing 100% oxygen in 3 ATM HBOT would lead to 14.3 more oxygen dissolved in the blood. This is based on the ratio (3 ATM x 100%) / (1 ATM x 21%) = 14.3.

But I since have realized that there are further complexities and discrepancies, because the partial pressure of oxygen inside the lungs is not the same as the partial pressure of oxygen of the air that you are breathing in. The oxygen partial pressure in the lungs is lower than the ambient air partial pressure. See this Wikipedia article for why.

So that makes my figure of 14.3 not very accurate. That's why I deferred to the figure of 20 times more dissolved oxygen from the 1953 study, rather than my calculated figure of 14.3. But the 14.3 figure is a reasonable ballpark figure based on very simple maths.

As far as I can see, because of these lung partial pressure discrepancies, there is no simple way to calculate this; you'd probably have to measure the actual dissolved oxygen level in the blood to get an accurate result.



@Hip do you know of any more recent publications where clinically significant concentrations of dissolved O2 are achieved using HBOT (in individuals with normal saturated hemoglobin)?

I have not seen any.
 
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rodgergrummidge

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@rodgergrummidge take a look at these studies and let me know what you think

There seem to be mechanisms at play beyond hemoglobin saturation.
  • Mitochondrial function (1) (2)
  • Blood flow to the brain and other organs (3) (4)
  • Healing neurological damage (5) (6)
  • Anti-viral and anti-bacterial effects (7) (8)
  • Autoimmunity (9) (10)
  • Studies on the use of HBOT for fibromyalgia, CFS/ME, and Lyme (11) (12) (13) (14)
I'm aware these studies are imperfect in their sample size / methodology / etc but given funding levels it's the best we have
Hi @Jesse2233 , thanks for list of refs above. I had a quick look over. IMO, the pubs listed are fairly weak being either i) animal studies which are difficult to interpret in terms of human disease, ii) in vitro studies where cells are exposed to 20% O2 which is vastly different to the O2 levels exposed to cells in the body or iii) published in non-ISI journals (eg the Lyme study) which is often associated with weak science that is poorly controlled.

But, I had a look over some other published studies to see how strong the evidence is for HBOT in the treatment of various diseases. My summary and thoughts are below:

Clinical use of HBOT: Hyperbaric oxygen therapy (HBOT) provides pure, 100% oxygen at a pressure that is much greater than the atmospheric level. HBOT has been used to treat a range of conditions and is clinically approved by the FDA to treat 13 conditions including:
  • CO poisoning
  • Decompression sickness and gas embolisms (eg. From diving and surfacing too quickly)
  • Radiation-induced tissue damage
  • Skin infections such as Clostridial Myonecrosis (gangrene caused by bacteria)
  • Chronic osteomyelitis that is unresponsive to standard surgical and antibiotic therapy
  • Trauma and tissue damage that disrupts the microcirculation and results in ischemia, edema, and tissue necrosis.
  • Increasing the oxygenation of skin grafts and reconstructive tissue flaps in order to increase the success of graft survival.
  • Acute anemia due to large loss of blood.
  • Wound healing in patients with poor circulation (eg. diabetic patients with microcirculation deficiencies)
HBOT and bacterial infections: HBOT has been shown to have anti-bacterial activity in some pathologies. Neutrophils and macrophages are amongst the first cells to arrive at damaged or injured tissue. Their role is to induce an inflammatory response that wards off bacterial infections so that the damaged/injured tissue can be repaired. The ability of the innate immune system (neutrophils and macrophages) to provide a first-line defence of damaged tissues against bacterial infections depends on a ready supply of O2. The defensive activities of neutrophils and macrophages are reduced in hypoxic conditions (low O2) and so there is an increased risk of infection. Neutrophils and macrophages require O2 to generate oxygen free radicals that are released as part of their "respiratory burst" that is used to kill bacteria. HBOT is thought to restore O2 levels in hypoxic tissues and so increase the ability of neutrophils and macrophages to defend against infection. In addition to its role in aiding bacterial killing by neutrophils/macrophages, increased O2 concentrations can be bactericidal for certain bacteria. So the increased O2 provided by HBOT may provide direct antibacterial activity. If a bacterial infection was the underlying cause of CFS, it is possible that HBOT might be of some benefit.

HBOT, pain and the treatment of fibromylagia: A number of clinical trials have provided evidence that HBOT can reduce pain symptoms.

1) In a clinical trial examining fibromylagia patients, fifteen 90-minute HBOT sessions at 2.4 atmospheres absolute (ATA) over 3 weeks significantly reduced the number of pain/tender points and pain threshold even after 1 HBOT session. The improvements obtained using HBOT persisted over the 15 sessions (J Int Med Res. 2004;32:263–267).

2) In another trial, HBOT was examined in post-trauma wrist pain using fifteen daily 90-minute HBOT sessions at 2.4 ATA. HBOT treatment reduced wrist swelling and pain after the final treatment. Reduced symptoms persisted 45 days post treatment (J Int Med Res. 2004;32:258–262).

3) In another Fibromyalgia trial, a HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2.0 ATA was examined. HBOT resulted in a decrease FMS pain symptoms. In addition, HBOT also provided some normalization of brain activity as measured by single photon emission computed tomography (SPECT) imaging. It was notable in this trial that patients often complained of symptom worsening during the first 4 weeks (PLOS ONE DOI:10.1371/ journal.pone.0127012).

One possible confounding issue in these human pain clinical trials is that the treatments cannot be blinded as the change of air pressure associated with HBOT is obvious to both staff and patients. Nonetheless, the findings are very encouraging.

HBOT and the treatment of CFS, mitochondrial diseases or fatigue. I couldn’t find any convincing publications examining the use of HBOT in any of the conditions associated with CFS including decreased mitochondrial functions, fatigue or recovery after exercise. Reference 12 cited above was published in an obscure journal of unknown quality in 2013 with no followup papers and so it is difficult to interpret the findings of that study.

Adverse effects of HBOT and potential clinical dangers. When used according to standard protocols within a clinical setting, and with O2 ATA not exceeding 3 atmospheres and treatment sessions limited to a maximum of 120 minutes, hyperbaric therapy appears to be relatively safe. Although rare, some deaths have occurred using HBOT in commercial non-clinical settings in several countries. Other adverse effects include reversible myopia, a consequence of the direct toxic effect of oxygen on the lens. Some patients may experience pain due to barotrauma if rupture of the middle ear or sinuses occur. Seizures due to HBOT can occur, but these are rare.

General HBOT conclusions: HBOT has been described as a “therapy in search of a diseases” (Chest 92:1074-82) which is very apparent from the proliferation of commercial HBOT clinics claiming to treat a wide range of conditions. The HBOT clinically approved protocols for treating the Bullet-Point conditions I listed above all use >2 atmospheres absolute (ATA). It is important to distinguish between HBOT which uses 100% O2 at >2.0 ATA and Normal Barometric O2 treatment (NBOT) that uses 100% O2 at 1.0 ATA. Several studies make the point that there is no evidence that 100% O2 at 1.0 ATA can provide any of the effects observed using clinical grade HBOT at >2.0 ATA. This is probably because of the vanishingly small increases in O2 dissolved in bodily fluids achieved by using NBOT with 100% O2 and 1.0 ATA (see the graph I posted earlier in this thread). NBOT that is commonly used in DIY home tents and masks may have no clinical activity for any condition or pathology. Thus, NBOT may be a waste of time, money and effort.

Conclusions regarding HBOT and the treatment of pain: Although there is no microscopic evidence of definitive pathology in the muscles/tissues of fibromyalgia patients, it is possible that hypoxia and ischemia may contribute to pain sensitization (Pain Manag. (2016) 6(4), 383–400). As outlined above, promising results have been published using HBOT performed in a clinical environment using >2.0 ATA in the treatment of pain. Thus, HBOT might be worth considering as an adjunct therapy for the management of pain in fibromyalgia and CFS..

To state the obvious, any HBOT treatment should always be performed under the supervision of clinically qualified doctors.

A Question: Has anyone made a compilation of costs for 15-50 HBOT sessions performed over 1-6 months in different clinics in different countries? It might be useful for individuals in decision-making as to whether HBOT might be a useful adjunct treatment for those of us with fibromylagia or CFS.

Rodger
 

voner

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@rodgergrummidge & Hip. a couple questions/thoughts.

would living at high elevations have any affect on HBOT's effectiveness? Say 5000 feet.....

The best evidence I’ve seen for causation of allodynia, which some fibromyalgia patients have, is ischemia in the micro vascular system. some researchers at McGill University published on it in 2008. I still can’t understand how HBOT help reduce allodynia, though....
 

bertiedog

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That does not sound very good. I hope you are going to be refunded.



I use the machine on the 75% oxygen at 2 liters per minute setting (which actually gives you more oxygen than the 90% at 1 liter per minute setting). I have not noticed much from using, apart from perhaps a slight improvement in my ADHD symptoms in the hours just after breathing the oxygen. I am using it for 1 hour daily, but not every day.

I have had this machine and one similar for the past 3 years and I use it on the 4 litre per minute setting and after 30 minutes maximum it gives me a big boost in energy. I notice especially first thing in the morning when I usually feel half dead. Most days I used it straight after I eat for 30 minutes and if I am not feeling great I will also use it after I have taken my dog for a walk.

Every time I use it I can feel the difference in my energy in my body but I have never used it at a lower setting because I don't believe I would feel any benefit at all.

Apart from my thyroid and adrenal meds the oxygen concentrator is the thing that helps me the most on a day to day basis.

Pam
 

rodgergrummidge

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@rodgergrummidge & Hip. a couple questions/thoughts.

would living at high elevations have any affect on HBOT's effectiveness? Say 5000 feet.....

The best evidence I’ve seen for causation of allodynia, which some fibromyalgia patients have, is ischemia in the micro vascular system. some researchers at McGill University published on it in 2008. I still can’t understand how HBOT help reduce allodynia, though....

Elevation has a big effect on the partial pressure of O2 (pO2) in the atmosphere. The partial pressure of normobaric oxygen in the atmosphere is dependent on the local atmospheric pressure and elevation above sea level. For example, the atmospheres absolute (ATA) in Denver, Colorado at 1625m is <1.0. Thus, a hyperbaric chamber would be necessary in Denver, Colarado if you wanted to breath O2 at 1.0 ATA (ie. the equivalent pO2 at sea level).

The higher in elevation you go, the greater the reduction in the partial pressure of O2. So if you go to very high elevations where the pO2 is less than 60mmHg, it is difficult to saturate your Hb with O2 and you would suffer shortness of breath and fatigue. But if you dial up 2.0 ATA on the HBOT, you will still get 2.0 ATA no matter where you are in terms of elevation. Its just that the difference between atmospheric pO2 at high elevations (<1.0 ATA) and the delivery of >2.0 ATA by HBOT becomes greater the higher you go in elevation.

But its difficult to answer your question as to whether the HBOTs effectiveness would be reduced at higher altitudes. Theoretically, I would suppose that living at higher altitudes and the consequent reduction in O2 dissolved in blood might reduce the overall effectiveness of HBOT where the aim is to try and increase the amount of O2 dissolved in blood.

Rodger
 

NotThisGuy

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So i think I'm ready to purchase an mHBOT. Thanks to crypto currency that was way faster than I thought :D

I guess my CFS triggers are Lyme and heavy metals, so mHBOT may be a game changer in my disease.

I'm still unsure what kind of mHBOT i should purchase. Seems like everyone needs a different pressure....

There is 1.3 ATA, 1.5 ATA and 2.0 ATA as an option... what you guys think would be the best?

@Jesse2233 any news about your progress with mHBOT?
 

MEPatient345

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Hi all, I’m starting HBOT at a hospital center tomorrow and will share here. It’s a center that typically treats for diving accidents, diabetes wounds and broken bones (so diff protocol to an MS center.) They treat at 2.3ATA which is 45 ft / 15 meters for one hour of treatment time a day for 4 weeks to start. A bit worried about the length/depth being high to begin with. They don’t give an option to do shorter.

I am housebound with the ability to leave the house for an hour a few times a month if I have good days. My steps range from 700 to 2000. I have had zero improvement in 4.5 years of being ill with any treatment. I’m not doing any other treatment at the same time, so I will know if this helps that it is purely because of it.

How are all of you progressing?
 

MEPatient345

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@voner I’ll be at a private hospital in Europe (pls PM me for exact location as it’s identifying information). It’s €120 a session if you buy 10 at once.

I am very classic ME, no comorbidities. Constant fatigue, PEM from any mental, physical or emotional stressors. Very bad sensory sensitivities to light, motion and sound that brings on PEM. Vision issues, like seeing the world in a dream. Cognitive problems: difficulties concentrating, taking in or learning new information. POTS.. can sometimes walk about 5 mins and then HR will go to 120, 130, 140 quickly. Usually it will be at 110 just making coffee. Headaches, 2 to 5 a week. Insomnia.
 
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