# CFS: 3 Phases, Toxicity and RNaseL



## Susan Purry (Nov 6, 2001)

I thought this article was very interesting. Worth a read if you have the time or the stamina. *The Three Phases of Chronic Fatigue Syndrome: Dr. Paul Cheney's Theory* http://www.immunesupport.com/library/showa...99&Reviewed=YES


> quote:ImmuneSupport.com10-23-2002 By Carol Sieverling Carol Sieverling of the CFS & FMS Support Group of Dallas-Fort Worth wrote this article based on transcripts of another member's visit with Dr. Paul Cheney, transcripts of a presentation he gave at a conference in Orlando in October 1999, and the tape of his seminar in Irving, Texas in May 1999. *CFIDS: The Big Picture *Paul Cheney, M.D., Ph.D., 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. *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. 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. *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. *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. *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. 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. 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. *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. © Carol Sieverling. http://www.virtualhometown.com/dfwcfids/.


The last section mirrors my own experienc of M.E/CFS very closely - 3 relapses, each lasting different times and with different levels of remission afterwards. What do you think? I have found the 3 phases happen in all 3 relapses of my M.E/CFS, and I'm glad to read a hypothetical explanation for it.


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## M&M (Jan 20, 2002)

Wow! That explanation sums up my experience pretty concisely. I think I am somewhere in Phase III at this point, as I am fairly comfortable inside my boundaries (which also include laying on the couch several hours each day) but crash when I try to come outside my boundaries. It does make sense. I'll be very interested to read his further research results! Thanks Susan! I don't know where you find all this stuff, but it sure makes me feel like I'm not so alone


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## Susan Purry (Nov 6, 2001)

Hi MrsMason, I'm glad to hear you're in Phase III







I can't take the credit for finding this artice; I subscribe to a number of email lists which just sends helpful info right into my inbox







Here's some more info, as you were asking about more of Cheney's research: *Paul Cheney, M.D., on Undenatured Whey for Chronic Fatigue Syndrome Patients* http://www.immunesupport.com/library/showa...15&Reviewed=YES


> quote:ImmuneSupport.com10-30-2002 By Carol Sieverling Author's note: This article is based on tapes of Carol Sieverlingï¿½s April 1998 and October 2000 visits to Dr. Cheney, and a transcript of a presentation he made in Orlando in 1999. He gave permission to share this information, but has not reviewed or edited it. Many Chronic Fatigue Syndrome (CFS) patients are taking [undenatured whey protein] based on the recommendation of nationally known CFS specialist Paul Cheney, M.D., Ph.D. These "undenatured" whey products are processed at lower temperatures than typical powdered whey protein. This requires a meticulous filtering process to maintain purity. The lower temperature preserves the fragile, but powerful, biologically active proteins, lactoferrin, and immunoglobulins in whey. What are the benefits of undenatured whey? It can address the glutathione deficiency that is virtually universal in CFS patients. Deficits in glutathione functionality show up as elevated lipid peroxide levels on the Great Smokies Oxidative Stress Test (www.gsdl.com), and also as elevated citrate and alpha ketoglutaric levels on the Great Plains Organic Acids Test, 913-341-8949. Glutathione deficiency has two major implications: detox failure and viral/microbial activation. Glutathione plays a major role in detoxification pathways. This deficiency impairs the body's ability to get rid of toxins, whether environmental or by-products of cellular metabolism. CFS patients slowly become toxic, storing away poisons in fatty tissue, muscles, organs and the brain. This cellular detox failure can make CFS patients "canaries to their environment". Detox programs that have been successful in other conditions can actually put some CFS patients in the hospital if their glutathione deficiency is not first addressed. Glutathione is also a powerful antiviral and anti-microbial weapon. Glutathione deficiency not only compromises antiviral and anti-microbial defenses, it also has a potent pro-viral effect. While the presence of glutathione inhibits viruses and intracellular organisms, its absence stimulates them. Glutathione deficiency actually augments viral replication. Anthony Falci, the top HIV researcher at the NIH, has shown that HIV growth can be completely stopped by raising glutathione levels in-vitro in cell cultures. If glutathione levels can be raised, the replication of almost any pathogen inside the cells can be stopped. Given the widespread reactivation in CFS of viruses like EBV, CMV, and HHV6, and the activation of microbes like mycoplasma, chlamydia pneumoniae and candida, finding a way to raise glutathione levels inside the cells has been a top priority of the Cheney Clinic. No treatment prior to the whey seemed to successfully address this deficiency. Supplementation, injections, and other interventions failed to significantly affect the glutathione levels inside the cells, where 90% of the body's glutathione is needed. Cheney found undenatured whey protein was the best way to increase glutathione levels and function. The clinic conducted a six-month study of the first patented bioactive whey product, and discovered it significantly improved glutathione function. Though it was a small study (eight patients), the results were consistent with the feedback from Cheney's patient population as a whole. Seven of the eight study participants finished the study. They all began by taking two packs a day. At the three-month point, half the group was switched to one pack a day. One patient had received so much benefit from two packs a day that he refused to take the lower dose and dropped out of the study. Five of the seven patients who finished the study had positive responses. The two who felt no benefit were the least ill to begin with. Cheney speculates that their healthier digestive systems might have more fully digested the whey, making it less effective. It's very important that all whey products be taken on a completely empty stomach so that no acid or digestive enzymes are present to break it down. Some patients even take an antacid 30 minutes before taking whey to reduce that possibility. Patients in the study were allowed to choose which tests would be run, since they were paying for them. Each patient who tested positive for mycoplasma and chlamydia pneumoniae at the beginning of the study tested negative six months after treatment, regardless of whether they finished the study with one or two packs a day. This suggests one pack a day will wipe out intracellular bacteria. Three patients were tested for HHV6. Two were positive. The patient who stayed on two packs a day the entire six months was negative at the end of the study. The patient who dropped to one pack a day remained positive. This suggests that at least two packs a day are needed to neutralize viruses. There is a "dose response" issue with [undenatured whey protein products]. Some who did not respond at two packs a day noticed real benefits at three. A few patients have even gone to five or six to reach maximum benefit. However, Cheney's recommended starting dose for [undenatured whey] is two packs a day. Increase the dose only if minimal or no benefit is seen, and give it a six-month trial. Each packet contains 10 gm, or 1.75 Tbsp. [Editorï¿½s note: Of course, each patient is different and should discuss appropriate dosage with their health care provider.] ï¿½ Carol Sieverling. Source: http://virtualhometown.com/dfwcfids/menu.html


I'll look out some more info on Cheney's research later in the week, I'm sure there's bound to be more somewhere (thank goodness for search engines!). Hope you have a good week,


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