Professor Martin Pall’s Research

As some of my readers may have already gathered: I’m really excited about Martin Pall’s research findings. If you watched the last video, The NO/ONOO-Cycle, a New Disease Paradigm, by Pall, you’ll know there’s a heck of a lot of stuff there. From the latest gene testing for hereditary markers and gene mutations to balancing our supplements and getting control of our reactions, this is Science-based treatment, peeps:


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.

More from Martin Pall:

“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 aetiology (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.”

A Summary of Pall’s 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.

Pall’s Research 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.

(This information is credited to Professor Martin Pall, provided by Clinical Education.)

Michellina Van Loder is a Professional Writer, Journalist and Blogger. This is where she shares her tales about trail blazing her way out of the Labyrinth of Chemical Sensitivities and Mould. This is also where you will find the latest Research on related topics.

The NO/ONOO-Cycle, a New Disease Paradigm, by Martin L. Pall

Today, I bring you this mind-riveting lecture on The NO/ONOO Cycle, a New Disease Paradigm from Professor Martin Pall, presented March 5, 2014 at the Bispebjerg Hospital in Copenhagen:

This is a 2.5 hour lecture by Dr. Martin Pall. Dr. Pall developed a protocol to correct problems with nitric oxide/peroxynitrite. His protocol overlaps quite a bit with the methylation protocols that many are familiar with, but has additional emphasis on nitric oxide, peroxynitrites, and antioxidants.

Dr. Pall believes NO/ONOO dysfunction lies at the heart of several disorders (heart disease, hypertension, fatigue syndrome, fibromyalgia, multiple chemical sensitivity, PTSD). Most of this lecture is a detailed explanation as to how these diseases relate to the NO/ONOO cycle.

I’ve [Judi Brooks] noted waypoints to save everyone time in accessing the video’s contents.

start……Intro to ideas and cycles
20:00…Downregulating cycle to reverse disease
25.38…Brief mention of systemic BH4 depletion
27:00…tendency for doctors to dismiss problems as psychological
29:40…treating cause rather than symptoms
30:45…34 mechanisms make up the NO/ONOO cycle, looking at heart disease
42.30…discussion of specific illnesses and how they relate to cycle

47:00…genetic basis of chronic fatigue (cortisol, ACE/angiotensin, inflammation, mitochondrial, superoxide)
50.30…testing his theory against new data (including BH4 depletion)
55.17…low BH4 in CFS, raised by sauna therapy
55.38…discusses GTPCH1 (i.e. GCH1), HSP90 protein and heat, sauna therapy
59.00…thalamus and cortisol and exercise
1.00.00…Saurez study on CFS and dramatic nitric oxide rise on exercise (rest!)

1.02.00…MCS pathways of action (pesticides, mercury), NMDA receptors
1.06.00…discussion of MCS, MSG sensitivity, CCK-B gene, dextromethorphan
1.09.30…Meggs study on inflammation, TRPV1 and TRPA1 receptors in MCS
1.11.00…Millqvist study on capsaicin, cough results in MCS
1.17.00…MCS genes (PON1 CYP2D6 NAT2 GSTM1 GSTT1 GSTP1 UGT1A1)
1.26.00…studies: Binkley’s CCK-B gene, Cui’s SOD-2 (superoxide dismutase)

1.35.00…discussion of Hetherington and Battershill, and rebuttal of criticisms

1.49.00…Electromagnetic hypersensitivity, microwaves, low-energy EMF fields
1.50.00…voltage-gated calcium channels; EMF opens cellular calcium channels
1.51.00…Released calcium causes effects; similarities between Ca & NDMA

1.54.00…Therapy ideas: 5-MTHF (methyfolate) as peroxynitrite scavenger
1.55.17…more on 5-MTHF; it increases methylation and lowers peroxynitrite
1.56.00…possible difficulty in tolerating high doses of 5-MTHF
1.58.00…high dose vitamin C helps 5-MTHF; 1 – 2.5g vit C will reduce ONOO
2.01.00…high vit C (1 – 2g) raises BH4 by converting BH3 back into BH4
2.02.00…IV vit C tried by some
2.03.10…hydrogen peroxide produced by IV vit C, may be anticancer in theory
2.04.00…H2O2 induces NRF2; as does zinc, curcumin, tocepherols (avoid alpha-tocepherol), silymarin, ellagic acid, green tea
2.06.00…sauna/heat’s main benefit may not be “detox” but by raising BH4
2.07.20…resveratrol raises SIRT1, which then raises BH4 and lowers superoxide, ONOO, and others
2.09.00…SIRT1 is NAD-dependent, but NAD is often low in NO/ONOO problem 2.09.14…take resveratrol with nicotinic acid (not nicotinamide) to raise NAD (Question: doesn’t nicotinic acid damage liver??)
2.11.00…use Mg-malate; magnesium deficiency increases NO/ONOO disease
2.13.00…omega-3 fatty acids; fish oil DHA and EPA;
2.14.00…cardiolipin, super oxide problem, heart failure
2.15.00…phosphlipids, phosphatidyl serine may go directly into mitochondria
2.16.00…L-carnitine and acetyl-l-carnitine help heart but may be mixed blessing
2.18.00…carotenoids useful, especially lycopene (tomatoes); activates NRF2
2.20.00… addendum slides on carotenoids, phenolic and thiol antioxidants
2.20.12…addendum slide on sauna therapy, BH4, and GTPCH-1 (GCH1)
2.20.17…addendum slide on glutathione, riboflavin, niacin, NADPH; using high-dose thiamine to increase NADPH via the pentose phosphate shunt
2.20.24…addendum slide on vitamin E (tocopherols and tocotrienols); 12-lipoxygenase enzyme
2.20.31…addendum slide on high-dose B12. HyroxyB12 is a NO scavenger.


International Sholarly Research Articles: (The 44 distinct mechanisms that make up the NO/ONOO-Cycle) Pulmonary Hypertension Is a Probable NO/ONOO Cycle Disease: A Review

The Labyrinth: Glutathione Nasal Spray

Michellina Van Loder is a Professional Writer, Journalist and Blogger. This is where she shares her tales about trail blazing her way out of the Labyrinth of Chemical Sensitivities and Mould. This is also where you will find the latest Research on related topics.

Information, products and views presented by guest bloggers @The Labyrinth are not necessarily the same as those held by this blog's author, Michellina van Loder. Reviews are my own personal opinions (unless stated otherwise); and satire is used throughout personal posts. Any health topics discussed are not to be taken as medical advice. Seek out medical attention if needed and do your own research; however, you're welcome to use mine as a start.
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