There are 9 current paradigms for disease such as infections, genetic mistakes, nutritional deficiencies, hormone dysfunctions, allergies, autoimmune conditions, cellular mutations, ischemic cardiovascular disease and amyloid (prion) diseases. Martin L. Pall Ph.D., in his book, Explaining “Unexplained Illnesses,” proposes a 10th. This paradigm proposes an explanation for such conditions as Chronic Fatigue Syndrome, Fibromyalgia, Multiple Chemical Sensitivity, Post-Traumatic Stress Disorder, and Gulf War Syndrome. He calls these illnesses, “multisystem illnesses.”

In addition, other illnesses may be due wholly or in part to this new paradigm. Among the candidates are tinnitus, post-radiation syndrome, multiple sclerosis, autism, overtraining syndrome, silicone implant associated syndrome, Sudeck’s atrophy, postherpetic neuralgia, chronic whiplash-associated disorder, amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease.

Dr. Pall’s book is quite technical and extensive and most of it is devoted to proving his theory which (very simplified) goes something like this:

Usually, an initial stressor such as infection, trauma, psychological distress, etc. in people genetically disposed to it, increases bodily nitric oxide (NO) production. Through a feedback mechanism, this level of nitric oxide remains high, whereas in those less disposed it returns to normal. High NO levels through many mechanisms cause oxidative stress and mitochondrial damage resulting in the many symptoms related to these illnesses. Since the NO level rise is local, the symptoms depend upon where the malfunction occurs.

Excess NO is acted upon by the free radical superoxide to form peroxynitrite, hence Dr. Pall’s name for his paradigm, the NO/ONOO¯ cycle (pronounced No! Oh No!)

Peroxinitrite is the main bad actor in this play but others are also formed in a rather complicated web of interrelated interactions. If you are interested in sorting out these interactions, how they affect the body, and why these unexplained illnesses can be explained by them, buy the book.

Some of the other results of this web are increases in inflammatory cytokines such as Il-6, Il-8, Il-1β, TNF-α, and INF-γ.

It also causes an increase in NF-κβ, increases in the activity of brain receptors NMDA, and Vanilloid, and increases in the NO synthases that make more NO.

Dr. Pall says there are no magic bullets that return the cycle to normal. It requires attacking each of these biochemical excesses to lower them and to protect and repair the mitochondria, the organelle in the cell that creates energy. In other words, a multimodal approach is needed. This approach should lower NO and peroxinitrate, lower NF-κβ and the inflammatory cytokines, supply powerful antioxidants, and lessen the NMDA and vanilloid receptors.

Based upon his “best guess” list of therapeutic substances and the lists he mentions which are used successful by various physicians, here are the basic nutriceuticals:

1. Glutathione. He recommends inhaled but liposomal may do as well.Acetyl glutathione is probably best.
2. Hydroxycobalamin is a form of Vitamin B12. He recommends inhaled, injected or sublingual forms. He says others such as cyanocobalamin or methylcobalamin will not work as well as NO scavengers.
3. Mixed natural tocopherols, especially the γ-tocopherol form of Vitamin E.
4. Buffered Vitamin C.
5. Magnesium as malate. It is presumed that Krebs cycle forms of magnesium or the addition of Malic acid would also help.
6. Four different forms of flavonoids including Ginkgo biloba, Cranberry, Silymarin, and Bilberry. Better than these (not in the book but endorsed by the doctor) is a form of Brown Kelp called Ecklonia cava.
7. Selenium as selenium grown yeast.
8. Coenzyme Q10.
9. Folic Acid.
10. Carotenoids such as Lycopene,Lutein, and Beta Carotene.
11. Alpha Lipoic Acid.
12. Zinc, Manganese, and Copper (modest dose for zinc and low dose for the others.)
13. Vitamin B6 in the form of Pyridoxyl Phosphate.
14. Vitamin B2 (Riboflavin) as Riboflavin 5’ –phosphate (FMN).
15. Betaine (Trimethylglycine).
16. Taurine.
17. Polyunsatured Phosphatidylcholine.
18. Acetyl-L-Carnitine.
19. Carnosine.
20. SOD.
21. To the book’s list might be added Shrubby Sophora, and Pyrroloquinoline quinone (PQQ).

What all these substances do and the reason for them may be found in the book. It also describes some outcomes from using them.