Q: Please explain how PTSD [Post Traumatic Stress Disorder] relates?

Dr. Pall: The severe psychological stress that initiates cases of PTSD can also, like the other stressors, produce increases in nitric oxide. So the initiation can involve the same mechanism as in these other illnesses. PTSD shares many symptoms and signs with these other illnesses, as well �?this is reviewed in Chapter 3 of my book. The question about PTSD is whether you can explain the characteristic psychiatric symptoms as being a consequence of the NO/ONOO- cycle. I do make arguments in my book that these can be explained as being caused by the cycle, but you will have to read the PTSD chapter to see what the arguments are. * * * *

 Q: What part do you think diet and antioxidants can play in controlling depression then, Dr. Pall?

 Dr. Pall: I'm not sure I can answer that, although I think that by down-regulating the NO/ONOO- cycle, all of the symptoms should improve at some point. I suggest in my book that excessive nitric oxide in certain parts of the brain has a role in generating depression, so this suggests that the nitric oxide scavenger hydroxocobalamin (a form of vitamin B12) may be especially useful in lowering depression. Not sure if there is any data on this. * * * *

Q: Realistically, how much benefit do you think the antioxidants you recommend can offer patients? And is there any research showing evidence of benefits yet?

Dr. Pall: I think there is much benefit. But the combinations of antioxidants must be well-chosen. Many people have had the notion that antioxidants are largely interchangeable and that one antioxidant is likely to be as useful as another. In fact, it is much more complex than that. And I think that the antioxidant trials that have been focused on using high dose synthetic alpha-tocopherol (the most commonly used form of vitamin E) and high dose synthetic beta-carotene have not been well thought out. * * * *

Q: Does a treatment plan for the cycle require a physician, or can it be implemented and maintained by the person suffering from the illness?

 Dr. Pall: I have worked with a leading supplement research company to develop an all over-the-counter nutritional protocol to lower the NO/ONOO- cycle biochemistry. [See "Antioxidant Suggestions for Down-regulation of the NO/ONOO- Cycle from Dr. Martin Pall, PhD." [http://www.immunesupport.com/library/showarticle.cfm?id=8075] ProHealth is working with this company to help make these preparations available. Again I must caution that these suggestions are intended as nutritional support, not as a replacement for medical treatment of any condition. Any decisions regarding a change in your healthcare plan or regimen should be made in collaboration with your professional healthcare team. * * * *

Q: How long does it take on the protocol to observe favorable results?

 Dr. Pall: I think as we have gotten better at this, the response has become more rapid. I'd expect to see a response in a few weeks, certainly in less than three months. I would add, however, that the approach requires that one avoid stressors that will otherwise up-regulate the NO/ONOO- cycle biochemistry. In CFS, that would include exercise as such a stressor - and many individuals may also have to avoid foods that they are allergic to, and psychological stress. It is important that the approach not only involves taking certain nutritional supplements but also avoiding anything that might otherwise up-regulate the cycle biochemistry. * * * *

 Q: Must all of the supplements from your protocol be taken to get full benefit, or can you take only a few?

Dr. Pall: I would expect that there will be a better response to all of them, or at least all of them that a person tolerates well. But individual components may, nevertheless, be helpful. For example, I have gotten some feedback from a group of people in Spain who are only taking the MVM-A part of the protocol and report favorable responses to that. I don't suggest that, but it nevertheless seems to be helpful to them. [Note: the MVM-A formulation is a multivitamin/mineral with acetyl-L-carnitine and R-alpha-lipoic acid.] * * * *

Q: In your protocol, do supplement dosages differ? In other words, do you make any distinction between a 200 lb man and a 110 lb woman? Often supplements don't make a distinction, and those of us who are small have problems.

Dr. Pall: No it does not, but clearly you may wish to consider this when deciding on your personal regimen. * * * *

Q: Can you over-use antioxidants?

Dr. Pall: Some antioxidants, especially when used alone and at high dose, can cause problems. And I criticize the use of high dose synthetic alpha-tocopherol (form of vitamin E) as well as high doses of synthetic beta-carotene, in my book. We have tried to consider possible negative effects of antioxidants in developing the Allergy Research Group protocol. * * * *

Q: I am a CFS patient. My uric acid level is typically below normal range. I understand that uric acid in the blood helps protect against peroxynitrite, and that the purine inosine can boost blood levels of uric acid. Do you think that supplementing with inosine might be helpful too?

Dr. Pall: There are three types of agents that may be expected to raise uric acid levels, and they may all be helpful. One is inosine �?others are D-ribose and RNA [ribonucleic acid]. Each has some positive aspects, but each may well have some drawbacks as well. I think that one or more of these may be worth trying. * * * *

Q: During a lecture by Dr. Paul Cheney he said he had seen adverse reactions to NAC [N-acetyl cysteine] supplementation. What dosage of NAC do you consider to be helpful?

Dr. Pall: NAC - N-acetyl cysteine - is well tolerated in most people, but Cheney has found that some of his patients do not tolerate it. We are using a low dose (about 40% of the usual dose) in the Allergy Research Group protocol, and suggest using it after starting to take magnesium. Magnesium should lessen any sensitivity to NAC. * * * *

Q: What can you do if you develop reactions to drugs, herbs, or various vitamins?

Dr. Pall: Avoid them or cut the dose. In some cases reactions may be due to impurities, in which case finding a purer source may be helpful. * * * *

Q: Are there certain amino acids that can be taken which will help the mytochondria to produce more energy?

Dr. Pall: Yes. I have tended to stay away from suggesting using amino acid supplements because they have so many complex interactions. But I may be wrong about this. The Petrovic protocol uses such amino acid supplements. [Note: This refers to a nonprescription CFS protocol developed by Nash Petrovic, MD, that reportedly includes "a complex mixture" of more than 200 microantioxidant compounds.] * * * *

Q: Could you please explain the use of Ecklonia cava extract (SEANOL-F)? It was recommended as a supplement that you use but it was not covered in your book. Thanks.

Dr. Pall: I’ve gotten some recent feedback from physicians that this polyphenolic antioxidant is very useful. It may well act in similar fashion to other phenolic antioxidants discussed in my book. * * * *

Q: Dr. Pall, is cod liver oil a good way to slow down the NO/ONOO- cycle?

Dr. Pall: Cod liver oil contains long chain omega 3 fatty acids, and these lower the induction of the inducible nitric oxide synthase. They should be helpful in this way. * * * * Q: Do you have an opinion on the use of malic acid for FM and/or CFS?

Dr. Pall: I suggest that magnesium malate may be the best form of magnesium to take. * * * *

Q: How does NO/ONOO- theory compare to Dr. Paul Cheney's model of a deficiency of 3 main enzymes, presented on video from 2006?

Dr. Pall: Dr. Cheney and I have spent many hours on the phone discussing CFS. Our views on it are very similar. This is apparent from the comments he kindly made for my book. [Note: Dr. Cheney stated in his review, "A stunning expose on what is surely a central thesis of chronic, unexplained, and fatiguing illness; namely that oxidative stress mechanisms hold the key to any holistic viewpoint....This book could easily mark the end of the beginning of a more complete understanding of this complex field, which is a trillion dollar nightmare of human misery and bio-political inattention."] * * * *

Q: What have other CFS and FM researchers said about your new ideas so far?

Dr. Pall: I got some great responses from the CFS people in England when I presented this recently. I have been invited back to keynote another CFS meeting in October. * * * *

Q: Does this abnormal NO/ONOO- cycle chemistry have any connection to the theory of the abnormal methylation cycle that some Drs. are talking about? [Rich Van Konynenburg, PhD’s glutathione depletion-methylation cycle block theory of CFS.]

Dr. Pall: This methylation concept is a very different concept from the NO/ONOO- cycle. I do think that a number of the agents suggested by those discussing methylation will help to lower the NO/ONOO- cycle �?so they may be useful for reasons that have nothing to do with methylation. In addition, the biochemistry involved in the methylation cycle is impacted by the NO/ONOO- cycle biochemistry. For example, the enzyme methionine synthase is inhibited by nitric oxide. * * * *

Q: Comparing Dr. Rich Van Konynenburg’s methylation cycle theory & the OH/ONOO- cycle, which concept do you think holds most promise for CFS & FM patients, and why?

Dr. Pall: We have communicated on this. The NO/ONOO- cycle mechanism is very extensively documented in my book, which contains about 1,500 references to the scientific literature. I have also published 16 papers on this mechanism. It is also much more complete than is Rich’s proposal, and provides detailed explanations for many features of these illnesses that have never been explained previously. * * * *

Q: I am on the Rich Van Konynenburg protocol. Can I combine yours for MCS with this?

Dr. Pall: There are a lot of overlaps between the two. I’d have to look at them in more detail to see if there any incompatibilities between them, but I suspect they are compatible. * * * *

Q: Isn't peroxynitrite a radical scavenger, which could greatly disrupt the energy production in the mitochondria? Do you think Dr. Robert Suhadolnik's work on the RNase L antiviral pathway could be the trigger which chews up the messenger RNA as well as the viral RNA - could be what is causing the NO and peroxynitrite problem?

Dr. Pall: Peroxynitrite attacks multiple components of mitochondria, and this is an important part of the NO/ONOO- cycle, and also contributes to symptoms. I don’t think we know how the 37 kD RNase L is involved �?at this point, we have a wide ranging explanation of CFS without involving this factor, but that does not mean it does not have a role. * * * *

Q: Do you think a pharmaceutical company could make and patent a drug that would break the free radical cycle?

Dr. Pall: I think there are drugs that are helpful, and others may be developed in the future that may be more so �?I talk about one possibility in my book that has substantial promise. But I think that the "magic bullet" approach to dealing with chronic diseases in general is dysfunctional. * * * *

Q: Is it possible to repair the superoxide dismutase production in the body?

Dr. Pall: There is a lot of experimental work on what are known as "superoxide dismutase mimics" �?relatively small molecules that get rid of superoxide. I don’t know what the prospects are for these being developed as effective drugs. * * * *

Q: Dr. Pall, do you believe the pharmaceutical company industry will lobby the drug insurance companies to block funding for supplements, or do you expect the medical industry in general to embrace your system?

Dr. Pall: The lobbying has been going on vigorously for quite a while. You should look at Dr. Jerome Kassirer’s book entitled On the Take �?it is very enlightening. * * * * Q: Do you think the NO/ONOO- protocol might change any over time?

Dr. Pall: I certainly hope so. I hope we will learn rapidly how to get an improved clinical response. And I think that many physicians and scientists will be involved in this process in the future, as they have been in the past. * * * *

Closing Chat Remark: Thank you, Dr. Pall, for all your hard work, and for helping those of us with MCS [and other unexplained illnesses] have real answers behind a perplexing illness that is "not all in our head." Bless you!

ProHealth also wishes to thank Dr. Pall - and all the patients, researchers, and advocates who participated so generously in this Live Chat Event. Hopefully the information exchanged here will help advance the work to find a cause and a cure. ____ *

Dr. Pall's book, Explaining "Unexplained Illnesses": Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Posttraumatic Stress Disorder, Gulf War Syndrome and Others [http://www.amazon.com/Explaining-Unexplained-Illnesses-Fibromyalgia-Post-Traumatic/dp/078902389X] (Haworth Press, May 2007), is available through Amazon.com [http://www.amazon.com/Explaining-Unexplained-Illnesses-Fibromyalgia-Post-Traumatic/dp/078902389X], and may be ordered at your local bookstore.

Note: This information has not been evaluated by the FDA. It is not medical advice and is not meant to prevent, diagnose, treat, or cure any illness, condition, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

©2007 ProHealth, Inc. By: [http://www.ImmuneSupport.com]