Cheney oxygen toxicity may determine outcome in CFS

Discussion in 'Fibromyalgia Main Forum' started by tansy, May 26, 2008.

  1. tansy

    tansy New Member

    Oxygen Toxicity as a Locus of Control for Chronic Fatigue Syndrome

    Paul R. Cheney MD, PhD

    Chronic Fatigue Syndrome is a disorder of unknown cause characterized by significant functional disability associated with fatigue, pain and neuropsychological complaints. The subject of oxygen utilization, and especially the lack of it in CFS, has been the focus of many investigations(1,2). Indeed, the response of oxygen utilization in CFS to maximum exercise (VO2 max) was used as an FDA approved end-point marker in the multi-center trial of Ampligen , a biological response modifier(3). These studies demonstrate that CFS patients use oxygen at a reduced rate for a normalized peak exercise activity.

    The oxygen response deficit with exercise in CFS is very appealing as an avenue of explanation for fatigue. Whether it is cause or effect, however, is unknown. We began our studies on oxygen itself by noting with echocardiography that patients with CFS had a much higher incidence of diastolic dysfunction than control groups(4). Diastolic dysfunction, especially in a younger cohort such as CFS, is most likely related to an underlying energy deficit(5). In addition, diastolic dysfunction, which is known to lower cardiac output, was shown to be associated with low cardiac output (CI < 3.0) in 80% of our CFS patients. Other studies have correlated (p<0.002) low cardiac output with CFS dysfunction and especially post-exertional fatigue(6). Low cardiac output can certainly cause lowered oxygen consumption but whether low cardiac output alone is responsible for low oxygen utilization is uncertain.

    Further echocardiography investigations of CFS in this clinic revealed, using saline contrast bubble studies, evidence of patent foramen ovale (PFO) in a shocking 90%(7), 4-5 times the expected result by chance alone and much higher than any other known PFO association. Such a finding raised the possibility of oxygen toxicity physiology in CFS. This study extends the relationship of oxygen utilization disorders common in CFS and examines the concept of oxygen toxicity as it might apply to CFS.

    During a ten-month period, 67 consecutive patients presenting for either initial or follow-up evaluation for CFS were evaluated using echocardiography coupled to a series of varied interrogations on the echo table in real time. After routine, though expanded echocardiography, each patient was evaluated for IVRT response before, during and after oxygen administration for 5 minutes each, initially at 4 lpm NC and then typically at progressively higher doses up to 40% FIO2 mask oxygen at 10 lpm flow rate if they were non-toxic to 4 lpm NC. IVRT or isovolumetric relaxation time is an internal timing measurement in milliseconds (msec) on echocardiography, which is inversely related to cellular free energy in myocardial cells. IVRT was measured in triplicate using continuous wave (cw) doppler and averaged for each result.

    In the 67 patient cohort, the average patient age was 49.3 (range 17-67). There were 48 females (71.6%) and 19 males (28.4%). Almost all the patients were fully or partially disabled and all had been ill for at least 5 years with the average length of illness being 14 years. Three patients did not meet severity criteria for CFS at the time they were evaluated and three were deemed atypical for CFS on clinical grounds. These six outliers were evaluated separately from the group. All 67 patients were categorized as either new patients or patients on various treatment algorithms if they were follow-up patients. The various treatment algorithms are complex as well as novel and cannot be fully discussed here but serve to illustrate the power of the proposed oxygen toxicity model to discriminate among various treatments.

    Controls (N=17) were selected to approximately match the CFS patients' age and sex distribution and were largely selected from the community. The average age was 45.0 (range 19-75). There were 10 females (59%) and 7 males (41%). All were either working or in school full time though 2 were non-medically retired and all were deemed functionally normal for age with no prior history of CFS though only a minority had unblemished medical histories.

    Because results depended on treatment status, the 67 patient cohort, as well as an additional 24 patients from a more limited evaluation cohort for a total of 91 patients, were segregated into a) new patients, b) patients treated in this clinic with standard therapies, c) patients treated in this clinic with standard therapies plus one novel, low molecular weight (LMW), cell signaling factor (CSF) peptide in a transdermal gel and d) patients treated in this clinic with standard therapies plus an expanded set of LMW, cell signaling factor gels. Of the 67 consecutive patients, less those who did not meet criteria for CFS and/or were deemed atypical (6 were so categorized), 26 were new patients and 25 of 26 or 96.1% were toxic to oxygen as evidenced by a rise in IVRT on exposure to oxygen and indicating a reduction in myocardial cellular energetics. It took three minutes or less to see this IVRT response take effect and 3-5 minutes to return to baseline once off oxygen. 26 of 26 new patients or 100% were toxic to 40% mask oxygen. This contrasts to 6 of 17 or 35% of the controls that were toxic to oxygen at 4 lpm and 11 of 17 or 65% of controls that were toxic to 40% mask oxygen. When patients from the group of 67 consecutive cases, excluding the 6 outliers as well as treatment responders, were statistically compared (N = 53) in their IVRT response on oxygen to the controls (N = 17) on oxygen at 4 lpm NC, there was almost no chance they could have been the same group (p < 0.0004).
    With respect to treated groups b), c) and d), there were 9 of 12 patients or 75% on standard therapy for at least three months who were toxic at 4 lpm and 12 of 12 or 100% toxic at 40% mask oxygen. There were 15 of 23 or 65% toxic on a single CSF gel therapy for at least three months and 23 of 23 or 100% toxic at 40% mask oxygen. Finally, there were 9 of 30 or 30% toxic on an expanded set of CSF gel therapies for at least three months and 8 of 14 or 57% toxic at 40% mask oxygen. Of special note in those patients receiving the expanded set of CSF's, was the fact that in a separate prospective study lasting one year of 16 patients on an expanded CSF therapy protocol, there was a 75% (12 of 16) clinical response rate with a mean Karnofsy Performance Scale (KPS) improvement of 10 points (p<0.006) in which the responders had an oxygen tolerance rate on 4 lpm of 92% (11 of 12) whereas the non-responders (25%) had a 75% rate of oxygen toxicity (3 of 4).

    There were a total of six patients out of the consecutive group of 67 fully evaluated patients who either did not fully meet the severity criteria for CFS (three were working full time but were otherwise typical for CFS) or were clinically atypical (three). From these two groups of outliers, all were tolerant to 4 lpm though 4 of 6 (2 from each group) or 67% were toxic to 40% mask oxygen, a result similar to controls. The interesting thing about the atypical group was that they all three had significant environmental illness and could be distinguished from controls by their real-time IVRT response to porcine liver derived CSF's suggesting that a defect in detoxification underlies their illness apart from oxygen toxicity.

    These results demonstrate that within certain well defined limits of the case definition for CFS, the relative cardiac cellular energetic response to oxygen in CFS (strongly negative) compared to controls (strongly positive to weakly negative) is significantly different (p < 0.0004). Furthermore, that the absolute response to oxygen (toxic vs. tolerant) yields 96% sensitivity (CFS being essentially a strongly oxygen toxic state) and 65% specificity compared to controls (35% are weakly toxic) at 4 lpm NC. At 40% mask oxygen, 100% of CFS cases are toxic, but so were 65% of controls. When patients were sub-categorized according to increasingly powerful treatment algorithms, they were increasingly transformed to an oxygen tolerant state, which in the case of the most powerful algorithm, was associated with a significantly (p<0.006) improved clinical status. We conclude that CFS is an oxygen toxic state and that oxygen toxicity status appears to determine outcome in therapeutic trials and is therefore, a locus of control in chronic fatigue syndrome.

    While it could be argued that this study simply reveals different levels of aerobic conditioning, there are several arguments against this including 1) the most oxygen responsive control had had a cardiac transplant five years ago and hasn't been able to do significant aerobic activity for five years and 2) this doesn't explain the oxygen tolerance found in the 6 atypical cases, all of whom were moderately to severely deconditioned, nor an oxygen toxic control who is a college athlete. Finally, the ability to transform the oxygen toxic state with ever more effective therapies, without an exercise program in place, suggests that the oxygen toxic state is related to some fundamental problem inherent to CFS.

    These findings appear to force a narrowing of potential causes of CFS because whatever pathophysiology one puts forth must explain universal oxygen toxicity in chronic fatigue syndrome and must explain a 90% incidence of PFO. In fact, it is the relative oxygen toxic state of fetal physiology, which is indirectly responsible for PFO, that is a key argument for the study interpretation. The missing piece to this puzzle may be that we see a super-select group of CFS patients at our clinic. While it is possible that we are masked off from other possibly non-oxygen toxic and less severe cases of CFS, this is not likely if they are disabled since we do see a wide spectrum of disabled patients from all parts of the US and abroad.

    It is also important to view oxygen toxicity as less a cause of CFS but rather a final common pathway whose presence is downstream from the issue of etiology or etiologies, though it appears to determine outcome. I strongly suspect that the emerging model of CFS as an oxygen toxic state will not be an etiologic based model but rather a model much like the cancer model. For example, there are many etiologies for cancer and many downstream complications and presentations, but only the cancer cell matters and ultimately determines outcome. Oxygen toxicity is analogous to the cancer cell in CFS and once established, may be independent of etiology but nevertheless, determines outcome.

    1. De Becker et al. "Exercise capacity in Chronic Fatigue Syndrome", Arch. Intern. Med. 2000 : 160 ; 3270

    2. Stevens,SR, "Using Exercise Testing to Document Functional Disability in CFS", Journal of Chronic Fatigue Syndrome", 1995:Vol 1, Numbers ¾; 127-129

    3. Strayer,DR., Carter,WA., Brodsky,I., Cheney,PR., Peterson,DL., Salvato,P., Thompson,C., Loveless,MO., Shapiro,D., Elsasser,W., and Gillespie,D., "A Controlled Clinical Trial with a Specifically Configured RNA Drug, Poly (I): Poly (C12U) in Chronic Fatigue Syndrome", Clin. Inf. Dis., Volume 18, Suppl. I, S88-95, January, 1994.

    4. Cheney,PR and Lucki,NC "Evidence for Diastolic Dysfunction in the Chronic Fatigue Syndrome enhanced by Tilt-Echocardiography: A study of ninety consecutive cases." IACFS Meetings, Jan 2007, Ft Lauderdale, FL

    5. Morgan,JP, "Abnormal modulation of calcium as a major cause of cardiac contractile dysfunction" NEJM 1991;325:625-632

    6. Peckerman,A,"Abnormal Impedance Cardiography Predicts Syndrome Severity in Chronic Fatigue Syndrome",The American Journal Of The Medical Sciences, 2003:Vol326,No2;

    7. Cheney,PR and Lucki,NC, "Evidence of Increased Frequency of Patent Foramen Ovale (PFO) in the Chronic Fatigue Syndrome with Enriched Oxygen Modulation of the PFO" IACFS Meetings, Jan 2007, Ft Lauderdale, FL
  2. Jayna

    Jayna New Member

    I fear there will be people terrified that breathing is poisoning them, and trying not to do it.

    It's a lot more complicated than that.

  3. Khalyal

    Khalyal New Member

    Thank you for posting this Tansy!

    Jayna, I agree. I'm not sure I have a handle on what exactly oxygen toxicity is.

  4. Jayna

    Jayna New Member

    As in scuba diving or premie incubators.

    Here's part of a physician-discussion (for pay) article that talks about oxygen toxicity in relation to familiar subjects to many of us: superoxides and antioxidants.

    "Hyperoxia is poorly defined, but probably exists whenever oxygen tension exceeds 21 percent of atmospheric pressure. [normal outdoor air - jayne]

    It appears to produce cellular injury through increased production of reactive oxygen species, such as the superoxide anion, the hydroxyl radical, and hydrogen peroxide [7] .

    When the production of these reactive species increases and/or the cell's antioxidant defenses are depleted, oxygen radicals can react with and impair the function of essential intracellular macromolecules, resulting in cell death [8].

    [snipped a bit of technical stuff about mice here - jayne]

    Hyperoxia may also increase susceptibility to mucous plugging, atelectasis, and secondary infection by impairing both mucociliary clearance and the bactericidal capacity of immune cells [16-21]."


    Since there's a growing body of evidence to suggest that CFS muscles are ineffective at aerobic [oxygen-burning] energy production, it's possible that's all Dr. Cheney is talking about: unused oxygen already in the bloodstream, being diverted to more toxic free radicals and damaging the cells.

    Don't you wish dr's spoke plain English????
  5. greatgran

    greatgran Member

    I don't understand. Someone explain.

  6. cct

    cct Member

    A few years ago, I asked my primary care physcian if I could have a tank of oxygen, and a mask, deliverd to my house.

    I was hoping that the forced oxygen would provide a source of rejuvination and increased energy.

    To my surprise, the pure oxygen made me more sick!

    I think that this is the type of reaction that Dr. Cheney is seeing in his study group. He does mention a reaction to "mask oxygen".
  7. Jayna

    Jayna New Member

    I hope my above post helps de-mystify oxygen toxicity.

    The only thing further reading is teaching me so far is that the pressurized oxygen masks they strap on trauma patients and during surgery can also cause damage to the lungs... apparently if they're left on for more than 16 hours at a time.

    I have an oxygen concentrator at home (have had for 2 years), which delivers 98% oxygen to my nose, but it's not pressurized. I use it for up to 20 hours on a really bad day. Its single biggest benefit is to shorten my immediate recovery time after exertion - from 30 mins to 10 after, for example, walking from the car to the house or being in a place with bad indoor air for a couple of hours.

    My visiting respiratory therapist said that my lungs were showing no ill effects from this level of use over this long stretch of time. So I'm not as worried about over-using this kind of oxygen as I would be if it was pressurized/mask delivered.

    But I'm re-thinking my use of oxygen with my overnight Cflex, since that does have pressure to keep my airways open. Not that I ever sleep for 16 hours - I'm lucky to get 8 or 9.

    So we PwC's are abnormal in our ability to use oxygen... what else is new?
    [This Message was Edited on 05/26/2008]
    [This Message was Edited on 05/26/2008]
  8. findmind

    findmind New Member the most astounding part of this article. That, my dear friends, is a hole between the two chambers of the heart; often dismissed by doctors when a patient queries them about it!

    Having COPD cannot help MY oxygen utilization at all, can it?

  9. beckster

    beckster New Member

    is that the same kind of hole that some years ago researchers found that persons with migraines had holes in their heart, and when the holes were repaired, the migraines also went away (actually, am not very clear, actually the study was primarily on persons with holes in the heart, but the docs noted that when they repaired the holes, the folks that also had had migraines, the migraines left . . . ) beckster
    [This Message was Edited on 05/31/2008]
  10. findmind

    findmind New Member

    that is the same one!

    one of my dau's had a stroke at age 40; she is fine now, but I read up on PFOs at that time, and besides migraines, they can cause strokes too.

    I think we had a thread here about PFOs once, can't remember in what context, though.

    I have gotten away from the original posting, I'm sorry!!

  11. Mikie

    Mikie Moderator

    In our Library here about efficient use of oxygen in the body. He gives a breathing exercise designed to more effectively utilize oxygen. It is a common exercise used in pulmonary rehab.

    I grew up at high altitude and that is supposed to make one more efficient at utilizing oxygen. That is why athletes train in high altitude environs.

    I have always noticed I would get an oxygen "high" from being in a room where it is in use. I'm not sure, however, that that is healthy for us. My doc told me he gets the same thing when he visits patients in the hospital and oxygen is in use.

    I'll see whether I can find his article and post it here. Thanks for posting this. It's very interesting.

    Love, Mikie
  12. Mikie

    Mikie Moderator

    Dr. Cheney on an Effective Breathing Technique Alternative to the “Rebreather” Protocol for Chronic Fatigue Syndrome

    by Carol Sieverling


    Editor’s Note: Dr. Paul Cheney, M.D., discussed a "new" breathing technique with patient Carol Sieverling – he presented it to her as no cost, easier, and more effective at increasing oxygen transport than the "rebreather" protocol. The following is a transcription from a conversation taped with Dr. Cheney by Carol Sieverling, that took place in November 2000.

    First, here are the benefits of increased oxygen:

    1) more energy at the cellular level

    2) suppresses growth of yeast (and other pathogens)

    3) prevents swelling of the brain caused by decreased oxygen

    Dr. Cheney said this was not uncommon in CFIDS and is the connection between Chiari Malformation and CFIDS. Dr. Cheney said that Chiari is a compression phenomenon due to lack of sufficient width/depth at the base of the skull, while CFIDS is a compression phenomenon due to anoxic cerebral edema. Many CFIDS patients are familiar with Dr. Cheney's earlier oxygen protocol using a partial rebreather mask to address tissue acidosis/blood alkalosis and thereby improve oxygen transport from the blood into cells (see for Cheney Treatment Plan Prescriptions).

    Dr. Cheney has realized this rebreather protocol, while beneficial, has limitations. It can be difficult to find the equipment, it is expensive, and the procedure requires much "tweaking." Most significantly, he has come to realize that it does not address the underlying problem of 2,3 DPG levels.

    2,3 DPG is a substance that allows oxygen to be released from the hemoglobin in our blood. Without 2,3 DPG, oxygen can't get off the hemoglobin and into the cells of our body. This oxygen deprivation makes the body switch over to anaerobic metabolism, which produces tissue acidosis, which can be painful. However, the more 2,3 DPG one has, the more oxygen is released from the blood into the tissues and organs and brain. (And oxygen will help kill candida and other pathogens.)

    The very simple breathing technique Cheney is recommending to all his patients can be found on Andrew Weil's tape of eight different breathing methods. This particular method is Weil's favorite - he says it's the most powerful way to treat chronic illness that he knows of. Ayurvedic physicians developed it 3,000 years ago. And 30 years of clinical experience now back it up.

    <b>Here is how it works:

    1) Inhale through your nose for 4 seconds

    2) Hold your breath for 7 seconds

    3) Exhale through tightly pursed lips for 8 seconds, creating "back pressure" (you should be able to hear the air being forced out of your mouth as you do this.)</b>

    Do this 8 times in a total of two and a half minutes. Do this twice a day - a grand total of 5 minutes a day. That's all it takes. (If you feel lightheaded, just do it 6 times or until you begin to feel lightheaded, then build up to 8.) You must be very faithful and consistent for this to work, and it takes weeks for the body to adjust the 2,3 DPG levels. But your oxygen transport will get better and better over time.

    What does this breathing exercise do? This method is based on the same principle at work in the marathon runners from Kenya who frequently win the Boston Marathon. They live and train at a high altitude. They run at 12,000 feet. To compensate for the lack of oxygen at higher altitudes, their bodies make a physiological adjustment, raising 2,3 DPG levels so more oxygen is released. The higher the 2,3 DPG goes, the easier it is to run. Then the Kenyans go to Boston, which is at sea level (with more oxygen in the atmosphere of course), and run their race. But their bodies are still set for high altitude, so they end up with more oxygen being transported into their tissues than other runners. They are superoxygenated, transporting oxygen like crazy.

    Dr. Cheney's goal is to “trick” our bodies into thinking we live at a higher altitude, thus raising our 2,3 DPG levels, thereby transporting more oxygen from our blood into our tissues. How is that done? By not breathing! This method is actually regulated breath holding. As you regularly breath hold, your O2 drops. You induce a state called desaturation. And for those five minutes a day of desaturation, your body panics. It believes it's high up in the mountains and it spends the rest of the day compensating for that (by raising 2,3 DPG), even though you're not actually up in the mountains. The body is so concerned with desaturation that even though you live in Dallas, for example, it will program your body as if you live in Denver (at a higher altitude).

    Besides being cheaper, easier, and more effective, Cheney says this method has another advantage over the rebreather mask: you can't "overregulate." With the rebreather mask you can "counterregulate" - the result is that you can get too much oxygen transfer going on, which will cause your body to lower 2,3 DPG, ultimately lowering oxygen transfer. This is why the rebreather stopped working for many of us after several months.

    With this breathing method, Cheney said that the body will raise 2,3 DPG to the point that it is beneficial, but it won't raise it so high that it "forces a more profound alkalosis" of the blood.
  13. beckster

    beckster New Member

    It seems ignoring or making little note of the PFO is a glaring thing. . . . Why do you think they dont emphasize this, especially when there is a procedure that can fix it . . . ?????????????????? Have good day, Beckster
  14. pw7575

    pw7575 New Member

    Just wanted to let you all know that the reason that Dr. Cheney doesn't talk about people getting the procedure to fix the PFO is because he believes it is dangerous.

    Here is a link to an article about why Dr. Cheney feels that this is a risky procedure.

    Take Care,
  15. beckster

    beckster New Member

    i still wonder why the serious finding of pfo's is not taken seriously. surgery is usually risky, but so is a progressive debilitating disease that slowly kills .. .

    still find this peculiar--maybe it is politics--cfs docs cant usually perform surgery, so it is neglected.

    Have there been studies when the pfo was fixed , that people got back life/energy/cognitive improvement along with the migraines stopping?

    thoughts anyone??????????????????/// Beckster
  16. beckster

    beckster New Member

    i did a little quick research on PFO's. They now do a noninvasive procedure, just go in through the groin. It eliminates migraines in about 50%, and in another 15% greatly reduces them. Sounds good to me. Also, leaving it open increases ones chances of stroke.

    I'm not interested in perfect cures or causes at this point (30 years later), just relief and as much quality of life as one can get. Even in the hole was closed and lasted 10 years, and then reopened, that's 10 years of more qualitly of life. It's simple procedure.

    I believe this is an extremely complex illness (infection, inflammation, chemicals, genomes etc) and they wont understand it in the next 50 years.

    I couldnt find how long the hole stays closed. If anyone finds this, please post and let us know.

    Also has anyone seen research of PFO's and other symptoms (other than migraines) that are relieved when the PFO is closed????????????????? Thanks, Beckster
  17. saving to read later....thankyou.

    love fran
  18. hi all,

    i wouldnt say that we need pure oxygen through using a face mask.

    but id say....

    we need to breath in the air that is outdoors,but not the actual chemicals from petrol/deasal fumes,and not the genetically modified crop spores either.

    so what are our options?

    well my only option right now is to stay indoors if its hot and very dusty outdoors.

    i feel i might try to go to the shop today,as its raining right now.the shop is up the road from my house.

    if i get in difficulty,someone near where i live,will help me back home,i feel sure of that.

    ive got net curtains up at all my houses windows.ive made a long one for near my front door too.

    this is a fine mesh,but the window nets,have large holes in them.

    when funds allow,im buying fine mess nets for all around the house.

    i need carpets gone in the bedrooms,but funds are low.

    my family refuse to keep the windows closed downstairs,so im having to be in my bedroom at 3pm onwards,when the family are watching telly,with the windows open.

    the sooner we get the finer mess, net curtains, at all windows the better, i feel.

    dont rely on oxygen tanks,we need to do this ourselves,and save the oxygen tanks for if we develope worse things,as we get older.

    re train your lungs to fully breath in air.

    i think with our short term memory problems,our brain is forgetting to tell our lungs how to breath.

    i wish i had the money to invent a sort of vest that would send pulses or something to our brain or lungs,to MAKE the lungs fully fill with air.

    i get bored and fatigued just having to concentrate on fully inflating my lungs,with air breathed in through the nose only..then its filtered.

    if i take my concentration off my breathing,i forget to breath.

    its a vicious circle for me right now.

    love fran
    [This Message was Edited on 06/12/2008]