Cheney's 1st Presentation May 22, 2008 (1 of 2)

Discussion in 'Fibromyalgia Main Forum' started by Rafiki, May 27, 2008.

  1. Rafiki

    Rafiki New Member

    Oxygen Toxicity as a Locus of Control for Chronic Fatigue Syndrome - Source: Presentation at 15th International Symposium of Functional Medicine, May 22, 2008

    by Paul R. Cheney MD, PhD

    [Note: This is one of two research abstracts that Dr. Cheney presented at the 15th International Symposium of Functional Medicine in Carlsbad, California on May 22. See also "Cell Associated Therapy for Chronic Fatigue Syndrome: Is this the Next Frontier?" It is part of his 3-hour opening speech – for which he received a standing ovation from 600 physicians and researchers from 14 countries - and was distributed on May 25 by Carol Sieverling on behalf of the CFS/FM Support Group of Dallas-Fort Worth ( via the Co-cure Listserv. The Institute of Functional Medicine ( has indicated it will offer a DVD of the presentation within 30 to 60 days. Broadly, “oxygen toxicity” involves excess oxygen concentration in body tissues.]

    Background: 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 AmpligenR , 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.

    Methods: 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.

    Results: 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.

    Conclusion: 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.

    Discussion: 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 3/4; 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, et al., "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

    from PH Library
    [This Message was Edited on 05/27/2008]
  2. Rafiki

    Rafiki New Member

  3. joanierav

    joanierav Member

    and what does he suggest we do for this? hes always finding the problems but doesnt have the treatment for the problems. joanierav
  4. joanierav

    joanierav Member

    just read cheneys part 2, and he does offer treatment. but i dont think i could find a doctor who would do these treatments. i know my primary wouldnt. i will have to wait and see what others will do. joanierav
  5. joanierav

    joanierav Member

    just read cheneys part 2, and he does offer treatment. but i dont think i could find a doctor who would do these treatments. i know my primary wouldnt. i will have to wait and see what others will do. joanierav
  6. Rafiki

    Rafiki New Member

    from an old post of yours

    "i was on nexavir cream for about 3 months. it didnt help me one bit. i had great expectations as i heard only good things about the kutapressin injections."

  7. Rafiki

    Rafiki New Member

    I understand it's usual not to improve much before 6 mo. but my brain is really running on empty now.

    Goodnight all,
  8. spacee

    spacee Member

    /we can never stop learning. Sorry the nexavir didn't work for you. Wish they had just redone the regular Kuta.

  9. slowdreamer

    slowdreamer New Member

    Don't get it..I know I need more fresh (Oxygenated ) air than Normal people so A/C is bad news but is he saying this??
  10. UsedtobePerkyTina

    UsedtobePerkyTina New Member

    Yeah, I admit I don't understand much of what he is saying. But I gather oxygen is toxic to our cells / body?

    Well, why do so many report improvement with increased oxygen?

  11. Rafiki

    Rafiki New Member

    Just to clarify: I never took Nexivar (Nexavir?:), that was joanierav.

    As to oxygen... I have no answers but I'm really looking forward to any dialogue that may result from this.

    Peace out,

    [This Message was Edited on 05/28/2008]
  12. Rafiki

    Rafiki New Member

    I, too, get the sense that a relevant test and some treatment options could result from Cheney's work.

    I went back and read some of his earlier papers and, with my VERY limited understanding, I find that Cheney consistently makes a great deal of sense and seems to avoid some of the huge leaps others are more willing to make.

    I'm optimistic. (I only wish treatment didn't involve parts of poor little piggies! I haven't eaten mammal in many decades.) So much of what has happened to me, and my test results, make total sense in Cheney's model.

    Looking forward to learning more!

    Peace to you,
  13. Rafiki

    Rafiki New Member

  14. dannybex

    dannybex Member

    I've never thought that oxygen was toxic -- in fact it's needed in order to kill off the buggers that may be infecting us.

    But looking online, I found this definition, which kind of helps explain Martin Palls peroxynitrate / antioxidant theory:

    "High concentrations of oxygen are known to increase the formation of free-radicals which harm DNA and other structures (see nitric oxide, peroxynitrite, and trioxidane).

    Normally, the body has many defense systems against such damage (see glutathione, catalase, and superoxide dismutase) but at higher concentrations of free oxygen, these systems are eventually overwhelmed with time, and the rate of damage to cell membranes exceeds the capacity of systems which control or repair it. "

  15. Rafiki

    Rafiki New Member

    why we feel "poisoned" after aerobic exercise, yes?


  16. Jayna

    Jayna New Member

    ... like the body is 'rusting' inside - that's what the peroxy-nitrate and super-oxides and so on are.

    I don't know why he used the word 'toxicity' unless it was to attract physicians' attention to the gravity of our situation. But I see he was using mask oxygen at up to 10 litres per minute - really pushing it into the patients - so he was, in effect, deliberately over-dosing them in ways that are flat out impossible for us to achieve by breathing on our own.

    Yes, rafiki, that's why we feel 'poisoned' by aerobic exercise. Because we are. And coping with all the 'toxic waste' produced by our own bodies puts a strain on all our major organs: heart, liver, guts, lungs and skin. Plus it repeatedly drains our reserves of chemicals (ie glutathione) needed to de-toxify all that crap.

    Probably part of our body's adaptive response to the super-oxides etc is to lower the amount of oxygen it draws in, so getting fresh air and even self-regulated oxygen supplements helps keep oxygen flowing to the rest of the body that still needs it. As long as we're not moving around, we're not drawing more oxygen to the muscles and not producing more toxic waste, so we feel better with some supplemental oxygen than without it. That's my theory, anyway.
  17. mcondon

    mcondon New Member

    What Cheney is calling "oxygen toxicity" is best thought of as a term he has come up with to describe the fact that echocardiography parameters deteriorate in almost all CFS patients who are put on oxygen (i.e. it is a sensitive test for identifying CFS.) This should not occur in healthy physiology. Response of echocardiography parameters to oxygen therefore might be a useful diagnostic tool that would rule out other possible causes of symptoms (and thereby might prevent the reliance on pyschiatric diagnoses by the medical community and disability insurers.) This should be viewed as a potentially positive development for CFS patients.

    As a patient of Dr. Cheney's, I will say that he does offer a very helpful therapeutic protocol. When I went to see him in 2001 after three years with CFS, I was barely holding on with my fingernails to my job. Since then, my condition has steadily improved. I am able to work full time and also have some activities outside of work. I am not cured, but I would take Cheney's protocols for this disease over the alternatives offered by other doctors and CFS specialists I have seen in the past.
  18. Rafiki

    Rafiki New Member

    Thank you both, very much, for your contributions to my understanding. I'm coming along slowly.

    Everything about my experience of the past 29 years (about half of it spent able to push and crash through a difficult but good life) has begun to make sense over the past few days. I'm more optimistic than I have been in a very, very long time.

    Mcondon, do you know where I can find the Cheney protocol in a GP friendly format online? My doctor is respectful of my intelligence and, so far, willing to educate herself with an open mind. Thanks.

    With Hope!

    [This Message was Edited on 05/29/2008]
  19. tansy

    tansy New Member

    He was one of the physicians who saw patients who became ill as a result of the Incline Village outbreak. The CDC unfortunately chose to interpret their findings somewhat differently and so began the construct of CFS.

    The outbreak at Incline Village was ME and that's why some of his articles make so much sense to us. I liked his description of the three stages of ME/CFS.

    I feel best in well oxygenated air but any aerobic activities would make me worse.

    Many specialists describe ME as a multi system illness with problems at a cellular level and have been doing so for several decades.

    I am having a short break, have other things to do right now, but I look forward to reading future discussions on Cheney's presentation and learning how that fits in with other research on ME and CFS.

    tc, Tansy
  20. Bluebottle

    Bluebottle New Member

    Thank you so much for posting this

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