Posted by TENA/DIAMOND on 3/26/2009, 3:04 am
Live Chat with Martin L. Pall, PhD – July 6, 2007: Professor of Biochemistry Explains Mechanisms of Chronic Fatigue Syndrome and Fibromyalgia & Suggested Protocol #1
July 9, 2007
Welcome to our Live Chat Event with Dr. Martin L. Pall, PhD, a Professor of Biochemistry and Basic Medical Sciences at Washington State University, and author of the acclaimed new book Explaining "Unexplained Illnesses."*
Dr. Pall has concluded that a single complex biochemical cycle which elevates levels of potent oxidants in the body – the nitric oxide/peroxynitrite cycle (NO/ONOO- cycle) – is responsible for causing CFS, FM, MCS, PTSD, and other chronic diseases. He believes this vicious cycle is initiated by a range of short-term stressors including viral and bacterial infections, toxic chemicals, physical trauma, and severe psychological stress. And a well-chosen regimen of antioxidants and other agents may help the body down-regulate that cycle. (For an expanded explanation of these concepts, click here. And for details of Dr. Pall's antioxidant protocol, click here.)
Importantly, as Dr. Pall cautions, “I am a PhD, not an MD, and none of this information should be viewed as medical advice. The supplements included in the antioxidant support regimen I have designed are not meant or sold as a treatment or cure for any disease.”
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Q: Dr. Pall, do you or someone close to you have one of these illnesses?
Dr. Pall: I had Chronic Fatigue Syndrome, but unlike most such people, I had a full recovery over a period of about a year and a half. I consider myself cured and have had no relapses over the past 8 years.
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Q: Was your illness directly related to something you could identify?
Dr. Pall: It was caused by a Varicella zoster infection – basically a bad case of shingles. Herpes group viruses are common initiators for cases of CFS, so this should not be surprising. They probably are active in this because they are very active in producing an inflammatory response.
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Q: What did you do to recover from your CFS?
Dr. Pall: I did three types of things. I was very careful to pay attention to what my body was telling me - specifically to avoid exercise. I think that response to exercise and perhaps other stress seems to be a specific defect in CFS. I talk in my book about what is the probable mechanism here. So this may be a good thing to observe but I think, in general, it is always good to pay close attention to many of the things your body is telling you.
I was very careful about my diet, knowing much about the biochemical properties of different foods, trying in general to give my body everything it might need in order to recover. I also took a number of nutritional supplements including antioxidants, magnesium, Co-Q10. However, it should be noted that you never know when you look at one person, what is producing a favorable response. So I think these things were important, but you can't say as a scientist that this has any validity.
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Q: How did you get started thinking about this cycle? What gave you the idea?
Dr. Pall: Peroxynitrite has a role in many different diseases, but what got me started on the vicious cycle idea was the work of Dr. Joe Beckman on the inactivation of the enzyme superoxide dismutase (in mitochondria) an enzyme that helps get rid of superoxide. His work suggested a possible vicious cycle - and what I have done is to look for other possible elements in cycles that can further contribute. Having identified additional elements in the larger cycle, the next step was to look to see if there was evidence for a role in the group of multisystem illnesses. [Note: Joseph Beckman, PhD, is a professor in the Department of Biochemistry and Biophysics, Director of the Environmental Health Services Center, and Principal Investigator of the Linus Pauling Institute at Oregon State University.]
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Q: Do you think there's a difference in the specific types of stress that cause the different illnesses?
Dr. Pall: Yes, there are stressors that are most commonly involved in the initiation of one illness but rarely involved in the initiation of others. For example the organic solvents and the pyrethroid and organochlorine pesticides seem to be most commonly involved in the initiation of Multiple Chemical Sensitivity (MCS). However, there is a fair amount of cross-talk, where stressors initiate more than one illness.
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Q: How is a “stressor” different from stress?
Dr. Pall: The term stress is used in two different ways, and is, therefore, ambiguous. Some people use the term to refer only to psychological stress, whereas others refer to stresses as being anything that perturbs the body. The term “stressor” is therefore clearer, referring to many different things that may perturb the body.
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Q: Why do you think some people develop this cycle after a stress, and not everyone?
Dr. Pall: There are important genetic, hormonal, and nutritional effects which, along with the strength of the stressors involved, determine who becomes ill and who does not.
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Q: So you think the nitric oxide cycle affects different tissues in the body rather than all at once?
Dr. Pall: Yes, it is local. And where it is localized in the body determines what symptoms and signs affect a particular individual.
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Q: Dr. Pall - I am confused about the nitric oxide [NO] cycle theory. I have heard that NO is good for our health. Can you explain a little more about it?
Dr. Pall: Nitric oxide has important functions in the body. It serves to dilate the blood vessels, it has an important role in the nervous system, and in controlling the immune system. However, when there are excessive levels and specifically when a lot of it is generating peroxynitrite, it can cause lots of problems. Let me say that one should not look at the NO/ONOO- cycle just in terms of nitric oxide - there are many different elements involved that are important.
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Q: What stabilizes the "vicious circle" of oxidative stress so the person has CFS [for example] but does not die?
Dr. Pall: The body still has protective mechanisms – it is just that they are not working adequately.
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Q: Dr. Pall, have you taken into consideration the possibility of genetic damage done by chemical, bacterial, or viral agents?
Dr. Pall: Yes, and peroxynitrite will break down to release hydroxyl radical that will cause genetic damage. There was a report that in CFS, damage to the mitochondrial DNA accumulates at a greatly increased rate, and this might be caused indirectly by elevated peroxynitrite.
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Q: Many people believe that the illness Myalgic Encephalomyelitis has, in this country, inaccurately ended up under the umbrella term ‘Chronic Fatigue Syndrome’. Does your theory treat them as one and the same (possibly differing only in severity and organs affected), or would you tend to believe that (the possibly infectious disease) M.E. is one of many stressors that can lead to chronic illness (chronic NO/ONOO- cycle) in its aftermath?
Dr. Pall: I treat them as being either similar or identical. I would say, in general, that this whole group of illnesses, with cases being so variable from one individual to another, constitute a whole spectrum of illness. Presumably this spectrum is generated by variations in the tissue distribution of the NO/ONOO- cycle biochemistry among different individuals.
So what we have are different diagnostic criteria or case definitions that basically identify some fraction of this spectrum as being some specific disease or illness. But the divisions are more or less arbitrary. A different case definition will change which part of the spectrum is included. This is important. These different illnesses don’t fall into discrete categories, in the same way that, for example, tuberculosis infection is different from an influenza infection or a cholera infection.
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Q: You mentioned exercise. Everyone tells us "all you need to do is exercise." How do we explain that is the wrong thing to do?
Dr. Pall: The phenomenon of post-exertional malaise in CFS is very well documented. So exercise leads to increases in the whole spectrum of symptoms in CFS. The question is why? I argue that it actually up-regulates the NO/ONOO- cycle mechanism by producing increased iNOS induction (more nitric oxide). You might look at the section of my CFS chapter on developing specific biomarker tests for CFS.
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Q: Do you talk at all about Fibromyalgia?
Dr. Pall: Chapter 8 in my book is on Fibromyalgia. It discusses both features that are similar to these other illnesses and also how the widespread excessive pain, the most characteristic feature of Fibromyalgia, appears to be generated.
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Q: Why do people with Fibromyalgia have more problems with free radicals versus the average population?
Dr. Pall: That is true for people with CFS and the other illnesses as well. Any time you have elevated levels of superoxide and peroxynitrite, you are going to have oxidative stress and excessive free radicals.
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Q: What causes the pain that no doctor seems to be able to find?
Dr. Pall: There is a difference between the Fibromyalgia pain and the pain found in this whole group of illnesses. The latter pain is similar to what is called hyperalgesia – excessive pain that has been studied extensively and which involves all of the elements of the NO/ONOO- cycle. So the presence of pain in these multisystem illnesses should not be surprising.
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