CFIDS and FMS Support Group of DFW

The Three Phases of CFS:
Dr. Paul Cheney's Theory

By Carol Sieverling, based on transcripts of another member's recent visit with Dr. Paul Cheney, transcripts of a presentation he gave at a conference in Orlando in October '99, and the tape of his seminar in Irving, Texas in May 1999. (The videotape can still be purchased.)

Table of Contents

  • CFIDS: The Big Picture
  • Phase 1: Viral Induced RNase L Activity
  • Phase 2:Xenobiotic Toxicity
  • Phase 3:Dynamic Hormone Response Deficits Induced By Hypothalamic Injury
  • Phase 3:DNA Gene Rearrangements
  • The Three Phases: A Personal Journey

  • CFIDS: The Big Picture
    Paul Cheney, MD, PhD, has treated over 5,000 CFIDS patients in the last 15 years. As many patients were followed over time, Dr. Cheney began to suspect that the illness moved through three distinct phases. One of our members saw Dr. Cheney recently, and he brought up a diagram on his computer and offered a refined version of his theory of the 3 phases of CFIDS. 

    The main problem in CFIDS is cellular metabolic dysfunction. The body's cells do not work very well. And every cell is affected. As a result, intracellular acidosis develops - the cells become more acidic inside. This is true of any chronic illness. What is specific to CFIDS are the arrows on the diagram. These are CFIDS-specific mechanisms by which CFIDS disrupts cell function. 

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    Phase 1: Viral Induced RNase L Activity 
    Let's start with Phase I illness. A virus usually triggers CFIDS. (A viral-like onset is reported by 70% of all patients.) The specific virus may not really matter. What matters is that RNase-L activity is initiated as a consequence of the viral assault. All viruses stimulate RNase L, but some more so than others. The mono viruses [herpes viruses such as EBV, CMV, HHV6?] most easily stimulate RNase L. 

    However, the trigger may not be a virus. RNase L is a defense against intracellular organisms, and a few unusual bacteria are intracellular. Therefore some bacteria, like mycoplasma and chlamydia pneumoniae, are possible triggers. Any intracellular organism that stimulates RNase L is a possible trigger for CFIDS, which is why the disease can look different among various patients in the beginning. 

    What does RNase-L do? It is designed to destroy messenger RNA at the cellular level. The good news is that it hits viral messenger RNA, stopping the virus from reproducing. But it also chews up human messenger RNA, inhibiting every enzyme in the body. Hence, CFIDS patients end up on their back. It is not the virus that makes them sick, so much as it is their body fighting the virus, specifically the RNase L activity. 

    Dr. Cheney had suspicions that this illness did change over time, but it was the discovery of a unique lower weight form of RNase L in many CFIDS patients, especially in the first five years of illness, that confirmed his suspicions. [For more on RNase L see The CFIDS Chronicle, Winter 2000, pg. 5, 1-800-442-3437; or our group's info pak.] 

    Research indicated that this aberrant form of RNase L was up to six times more destructive than the typical form. When Dr. Cheney saw these results, (based in part on blood samples from some of his own patients), the hair on the back of his neck stood up. He had always known that CFIDS patients were very sick, but he didn't really understand why. The burning question for him had been "Why are these people so sick?" With the discovery of the low weight RNase L, the question became "How are these people surviving?" 

    What is supposed to happen when a healthy person encounters an intracellular organism? The regular form of RNase L inhibits viral replication, the immune system revs up and wipes out the virus, then everything down-regulates, and they recover. 

    But unfortunately that is not what happens in CFIDS. In this illness, the RNase L activity shifts to the more destructive lower weight form and does not shut off. It stays activated much longer, resulting in pronounced cellular metabolic dysfunction, which ultimately affects the liver. Liver function declines because the enzymes used by the liver are being creamed by the activity of the aberrant RNase L. 

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    Phase 2:Xenobiotic Toxicity 
    The shift to Phase II occurs when patients become susceptible to toxins, because RNase L degrades enzymes that the liver needs to effectively detoxify the body. The most common source of toxicity is the gut. For some, it might be the gut AND the mouth [root canals and cavitations]. For others, it might the gut AND the mouth AND their environment. 

    The real problem is not usually the gut, it is the inability to detoxify the gut. Everyone has a toxic gut, but healthy people have livers that prevent them from getting hurt by that toxicity. Everyone has a toxic mouth - and root canal teeth and cavitations are toxic - but healthy people have defense mechanisms to defend themselves. The environment is toxic, but healthy people have defense mechanisms. What CFIDS patients are losing, courtesy of RNase L, is their detox defense. 

    In CFIDS the toxicity that the liver normally gets rid of now comes roaring into the systemic circulation. Then patients shift from Phase I to Phase II. That shift usually sounds like this: "You know, I felt like I had the flu or mono - and then my disease changed. The sore throats went away, the glands got better, the fever came down - but now I'm even sicker. My basic problem now is that I can't think anymore. My fatigue is worse than ever. And I'm beginning to hurt - a lot." Although 10% of patients do not have much pain. 

    Whether patients have pain appears to depend on the type of toxins involved. So, there's some variability in pain. But the loss of brain function and the severity of the fatigue are certainly driven by toxicity. The Toxicity Phase has a different "feel" than the RNase-L Phase. 

    Phase I can last weeks or months, or for some people, years. Phase II can last for a decade - or longer. Phase II can be a very long-winded problem, even though during this phase, the RNase-L activity can down-regulate back to normal. 

    So the question is, "When the RNase-L down-regulates, why don't patients get better?" The primary reason is that once the toxicity begins, the toxins themselves can then inhibit the very enzymes necessary to detoxify. So it's a self-fulfilling feedback loop. The toxins themselves injure the enzymes needed to get rid of the toxins. So Phase II can go on for a lot longer than Phase I. 

    The second reason is the "Staten Island effect". If you dumped garbage from Manhattan on Staten Island for a decade and then stopped, how long would it take to get it clean? Probably a lot longer than a decade. Once you dump toxicity into the body, especially the types of toxins we're talking about, for any length of time, it can take a lot longer to get rid of them than it took to get toxic in the first place. 

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    Phase 3:Dynamic Hormone Response Deficits Induced By Hypothalamic Injury 
    The transition to Phase III happens next - if patients are lucky, and most are. Phase III has a different sound to it. The toxins, in addition to inhibiting cell function, have invaded the central nervous system and injured deep brain structures, especially the hypothalamus, resulting in problems with virtually every hormone in the body. The actual problem is with the loss of "dynamic hormone response". This means that hormones that should rise and fall according to signals or demands from the body do not respond accordingly. The hypothalamus' major function is to control dynamism. Injuring the hypothalamus leads to a loss of dynamic response, such that patients can experience great difficulty in handling the normal stresses and strains of life. 

    What does Phase III sound like? "Within my boundaries, I don't feel too bad. I'm pretty comfortable. My problem is that every time I try to exceed those boundaries, I crash. I get worse. So I haul back within my boundaries, and I'm now comfortable again." With the loss of dynamic hormone response, patients cannot cross boundaries. Crossing boundaries requires dynamic response capability, and they no longer have it. In addition to the problems with dynamic hormone response, Phase III may also involve damage to the DNA of energy producing mitochondria. The loss of a portion of mitochondria puts an energy ceiling on patients. 

    The extent of the boundaries can vary among patients, depending on the amount of injury done during the first two phases. By no means is everyone home-bound or bedridden. And there is hope. Dr. Cheney does not believe the endpoint of Phase III is totally fixed. There is a good deal of plasticity to the central nervous system, and there can be significant resuscitation of brain function, and perhaps even the mitochondria may not be completely lost. 

    It is possible to have elements of all three phases going on at once, but usually there is a dominant phase. But if you look at how people change over time, CFIDS patients are all headed for Phase III - a point in time when they're pretty comfortable within their boundaries. 

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    Phase 3:DNA Gene Rearrangements 
    The Gene Rearrangement is the fourth arrow on the diagram. Patients are actually juggling their genetic code to find help. They're playing a poker game in which they are shuffling their genetic deck to find a hand capable of helping them. The winning hands are duplicated. The losing hands are not. The problem is, patients have a lot more losing hands than winning hands. But they compensate by only propagating the winning hands. Is this genetic shuffling a net problem or a net benefit? It could be either way. [An article on this gene rearrangement appeared in our January 2000, and was reprinted in the Winter 2000 CFIDS Chronicle: 1-800-442-3437. 

    We hope to do a follow-up article on treatments for each phase. Cheney spoke about them in this recent conversation, but those tapes have not yet been transcribed. According to information I already have, a few drugs and a variety of supplements can minimize suffering and injury during all phases. (See Cheney's Treatment Protocol in our info pak or on our website.) 

    The "heavy hitter" for Phase I patients who have high levels of the aberrant RNase L is the extremely expensive IV drug Ampligen, which is in phase III FDA trials. It appears to down-regulate the aberrant RNase L, at least in some patients. 

    The "heavy hitter" for the detoxification needed in Phase II is the undenatured whey. The whey is also a powerful weapon against intracellular organisms. The treatment Cheney is currently researching for Phase III brain resuscitation is injection of fetal bovine growth factors.

    And there is always the hope and promise that our body's own healing mechanisms will shuffle our genetic code and come up with the winning hand that will significantly increase our functionality, or even restore us to health. Never under estimate the body's own healing mechanisms. Dr. Cheney doesn't. 

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    The Three Stages: A Personal Journey

    I asked Dr. Cheney about my unusual pattern of three separate onsets of CFS with complete, or nearly complete, recoveries in between each episode. Each onset was worse, hitting harder and faster, with more symptoms. And each episode lasted longer. While each left me bedridden for months, the first episode lasted only 14 months, the second almost four years. The current one began in early 1996 and is still ongoing. I am largely home-bound and confined to lying on the couch many hours a day. 

    I asked how the phases applied to my history - could I have cycled through all three phases with each episode? He said yes. It was likely that my RNase L had down-regulated very quickly the first time, doing relatively minor damage and allowing me to make a good recovery. He said it sounded like a slight touch of Phase I, months of Phase II, and very little if any Phase III, since I fully recovered. 

    With the second episode we suspect the RNase L down-regulated fairly soon, though not quite as quickly as before, again minimizing the damage and allowing me to make a 95% recovery. The theory is a little of Phase I, mostly Phase II, and a touch of Phase III. 

    During the third episode we know the RNase L was upregulated for a longer period, not only by my clinical symptoms, but by the RNase L test results. They showed that some of the destructive lower weight RNase L still remained in 1998, two years after the onset of the third episode. The test is done in Belgium at RED (RNase L Enzyme Deficiency) Laboratory.

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    Update 01/10/05. For questions or comments concerning this site, please contact Lori or Deborah.

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