Prof. Martin Pall PhD: Nutritional Updates on Complex Diseases

Professor Martin Pall presented his hypothesis on complex disease management for us in 2007 and three years later has returned to bring us up to date on the clinical and research developments that have taken place during this time.

His one day seminar was held at the Royal Society of Medicine on the 16th of April 2010.

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Prof. Martin Pall

Prof Martin PallIs Professor Emeritus of Biochemistry and Basic Medical Sciences, Washington State University and Research Director, The Tenth Paradigm Research Group. After personally developing chronic fatigue he began to investigate the biochemistry of the illness. His work allowed him to construct a well received theoretical hypothesis, which has been explored in thousands of patients with good outcomes. Martins continued intellectual pursuit of improving the NO-ONOO theory has created additional strategies designed to hasten recovery from a variety of complex, but biochemically related illnesses. This one day seminar will discuss the mechanisms behind the chronic state people become locked into, uncouple the therapeutic interventions, describe case histories and research experiences and discuss clinical strategies available today.

Testimonial

Having had CFS/ME for nearly 17 years, with fibromyalgia for the past 9 years, I have tried all manner of treatments with varying degrees of success. After the first 2 months on Martin Pall’s protocol, I began to experience good and sustained results: the ‘brain fog’, muscle twitching, tinnitus and fibromyalgia I had suffered daily had all eased greatly.

I still suffer symptoms daily, but they are not omnipresent. They are much milder and less troublesome than before using the protocol. This is the most convenient and consistently effective treatment I have used since badly relapsing in 2001, and 18 months after beginning the protocol, I continue to use it and benefit from it.

In the interests of greater convenience and product freshness, I wonder whether having the pills packaged in blister packs, rather than the several containers currently in use, might be more advantageous. If that is a criticism, then it is my only one.

D Moore, County Durham

Summary of Hypothesis

The NO/ONOO- cycle is a biochemical vicious cycle that is thought to cause such diseases as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), multiple chemical sensitivity (MCS), fibromyalgia (FM) and possibly a large number of other chronic inflammatory diseases.

figure 1

Vicious (NO/ONOO-) cycle diagram. Each arrow represents one or more mechanisms by which the variable at the foot of the arrow can stimulate the level of the variable at the head of the arrow. It can be seen that these arrows form a series of loops that can potentially continue to stimulate each other. An example of this would be that nitric oxide can increase peroxynitrite which can stimulate oxidative stress which can stimulate NF-kappaB which can increase the production of iNOS which can, in turn increase nitric oxide. This loop alone constitutes a potential vicious cycle and there are a number of other loops, diagrammed in the figure that can collectively make up a much larger vicious cycle. The challenge, according to this view, in these illnesses is to lower this whole pattern of elevations to get back into a normal range. You will note that the cycle not only includes the compounds nitric oxide, superoxide and peroxynitrite but a series of other elements, including the transcription factor NF-kappaB, oxidative stress, inflammatory cytokines (in box, upper right), the three different forms of the enzymes that make nitric oxide (the nitric oxide synthases iNOS, nNOS and eNOS), and two neurological receptors the vanilloid (TRPV1) receptor and the NMDA receptor.

These four illnesses, chronic fatigue syndrome (CFS/ME), multiple chemical sensitivity (MCS), fibromyalgia (FM) and post-traumatic stress disorder (PTSD) often occur together in the same individuals (they are comorbid) and share many symptoms in common (1,2).  They also share a common pattern of case initiation:  Each is often initiated (that is started) by a short-term stressor only to be followed by chronic illness that typically lasts for years and most often for life.  These various similarities and overlaps among these four have led many scientists to suggest that they may share a common etiology (cause), however they have been uncertain what the cause may be.  I will call these four illnesses multisystem illnesses, following the lead of some others, and will challenge here the claims they are unexplained and that even their symptoms are unexplained.  What many have called the Gulf War Syndrome is a combination of all four.

  1. Short-term stressors that initiate cases of multisystem illnesses act by raising nitric oxide synthesis and consequent levels of nitric oxide and/or other cycle elements.
  2. Initiation is converted into a chronic illness through the action of vicious cycle mechanisms, through which chronic elevation of nitric oxide and peroxynitrite and other cycle elements is produced and maintained.  This principle predicts that the various elements of the NO/ONOO- cycle will be elevated in the chronic phase of illness.
  3. Symptoms and signs of these illnesses are generated by elevated levels of nitric oxide and/or other important consequences of the proposed mechanism, i.e. elevated levels of peroxynitrite or inflammatory cytokines, oxidative stress and elevated NMDA and vanilloid receptor activity.
  4. Because the compounds involved, nitric oxide, superoxide and peroxynitrite have quite limited diffusion distances in biological tissues and because the mechanisms involved in the cycle act at the level of individual cells, the fundamental mechanisms are local. The consequences of this primarily local mechanism show up in the multisystem illnesses through the stunning variations one sees in symptoms and signs from one patient to another.  Different tissue impact of the NO/ONOO- cycle mechanism is predicted to lead to exactly such variations in symptoms and signs.  One also sees evidence for this fourth principle in published brain scan studies where one can directly visualize the variable tissue distribution in the brains of patients suffering from one of these illnesses.
  5. Therapy should focus on down-regulating the NO/ONOO- cycle biochemistry.  In other words, we should be treating the cause, not just the symptoms.
CPD Approval Credits/hours
British Association for Applied Nutrition and Nutritional Therapy British Association for Applied Nutrition and Nutritional Therapy 4.5
The Royal College of Physicians has awarded CPD credits for the seminar: Royal College of Physicans (RCP) 5

Publications include

  1. Pall M.L.  (2007)  Explaining “Unexplained Illnesses”:  Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromylagia, Post-Traumatic Stress Disorder, Gulf War Syndrome and Others.  Harrington Park (Haworth) Press, New York. Purchase from Nutri-Link
  2. Pall M.L.  (2000)  Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome.  Med Hypotheses 54,115-125. View Abstract
  3. Pall M.L.  (2001)  Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite.  Med Hypotheses 57,139-145. View Abstract
  4. Pall M.L.  (2002)  NMDA sensitization and stimulation by peroxynitrite, nitric oxide and organic solvents at the mechanism of chemical sensitivity in multiple chemical sensitivity.  FASEB J 16,1407-1417. View Abstract
  5. Pall M.L.  (2008)  Post-radiation syndrome as a NO/ONOO(-) cycle, chronic fatigue syndrome-like disease.  Med Hypotheses 71: 537-541. View Abstract
  6. Pall M.L.  (2006)  The NO/ONOO- cycle as the cause of fibromyalgia and related illnesses:  Etiology, explanation and effective therapy.  In:  New Research in Fibromyalgia, John A. Pederson, Ed., pp 39-59, Nova Science Publishers, Inc., Hauppauge, NY.
  7. Pall M.L., Anderson J.H.  (2004)  The vanilloid receptor as a putative target of diverse chemicals in multiple chemical sensitivity.  Arch Environ Health 59,363-372. View Abstract
  8. Pall M.L., Satterlee J.D.  (2001)  Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress disorder.  Ann N Y Acad Sci 933,323-329. View Abstract
  9. Pall M.L.  (2009)  The NO/ONOO- cycle mechanism as the cause chronic fatigue syndrome/myalgic encephalomyelitis.  In:  New Research in Chronic Fatigue Syndrome, John A. Pederson, Ed.,  Nova Science Publishers, Inc., Hauppauge, NY, in Press. View Abstract
  10. Pall M.L.  (2009)  Multiple chemical sensitivity:  toxicological questions and mechanisms.  Wiley & Sons, New York, in press.
  11. Pall M.L.  (2007)  Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO- cycle.  Med Hypotheses 69,821-825. View Abstract
  12. Pall M.L., Bedient S.A.  (2007) The NO/ONOO- cycle as the etiological mechanism of tinnitus. Int Tinnitus J 13,99-104. View Abstract

Publications include

1.Pall M.L.(2007)Explaining “Unexplained Illnesses”:Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromylagia, Post-Traumatic Stress Disorder, Gulf War Syndrome and Others.Harrington Park (Haworth) Press, New York. Purchase from Nutri-Link

2.Pall M.L.(2000)Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome.Med Hypotheses 54,115-125. View Abstract

3.Pall M.L.(2001)Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite.Med Hypotheses 57,139-145. View Abstract

4.Pall M.L.(2002)NMDA sensitization and stimulation by peroxynitrite, nitric oxide and organic solvents at the mechanism of chemical sensitivity in multiple chemical sensitivity.FASEB J 16,1407-1417. View Abstract

5.Pall M.L.(2008)Post-radiation syndrome as a NO/ONOO(-) cycle, chronic fatigue syndrome-like disease.Med Hypotheses 71: 537-541. View Abstract

6.Pall M.L.(2006)The NO/ONOO- cycle as the cause of fibromyalgia and related illnesses:Etiology, explanation and effective therapy.In:New Research in Fibromyalgia, John A. Pederson, Ed., pp 39-59, Nova Science Publishers, Inc., Hauppauge, NY.

7.Pall M.L., Anderson J.H.(2004)The vanilloid receptor as a putative target of diverse chemicals in multiple chemical sensitivity.Arch Environ Health 59,363-372. View Abstract

8.Pall M.L., Satterlee J.D.(2001)Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress disorder.Ann N Y Acad Sci 933,323-329. View Abstract

9. Pall M.L.(2009)The NO/ONOO- cycle mechanism as the cause chronic fatigue syndrome/myalgic encephalomyelitis.In:New Research in Chronic Fatigue Syndrome, John A. Pederson, Ed.,Nova Science Publishers, Inc., Hauppauge, NY, in Press. View Abstract

10.Pall M.L.(2009)Multiple chemical sensitivity:toxicological questions and mechanisms.Wiley & Sons, New York, in press.

11.Pall M.L.(2007)Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO- cycle.Med Hypotheses 69,821-825. View Abstract

12.Pall M.L., Bedient S.A.(2007) The NO/ONOO- cycle as the etiological mechanism of tinnitus. Int Tinnitus J 13,99-104. View Abstract

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