Martin L. Pall, PhD, is a Professor Emeritus of Biochemistry and Basic Medical Sciences, Washington State University, Pullman, Washington, U.S.A. He states that he developed Chronic Fatigue Syndrome (CFS) from a varicella zoster virus infection in the later 1990s but has made a full recovery by following a program of avoiding exercise, diet changes, and taking supplements that decrease inflammation.
- 1962 - B.A., Johns Hopkins University, Baltimore, MD
- 1968 - Ph.D., California Institute of Technology, Pasadena, CA
Dr. Pall developed the Nitric Oxide Cycle Theory, also, called the NO/ONOO-cycle (pronounced "no-oh-no" cycle) which states that this biochemical cycle causes the inflammation present in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), Multiple Chemical Sensitivity (MCS), fibromyalgia (FM) and possibly a large number of other chronic inflammatory diseases such as heart disease. "Nitric oxide, acting via its product peroxynitrite, a potent oxidant, acts to initiate a biochemical vicious cycle which is the cause of illness," explains Dr. Pall.
He believes that certain over-the-counter supplements, such as fish oil, CoQ10, vitamin E, NAC (N-acetylcysteine), magnesium, and other antioxidants, can help downregulate the oxidation caused by the nitric oxide cycle. He believes Vitamin B12 injections can also be a potent nitric oxide scavenger.
- 2007, Explaining "Unexplained Illnesses": Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, and Gulf War Syndrome
- 2010, How Can We Cure NO/ONOO− Cycle Diseases? Approaches to Curing Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Fibromyalgia, Multiple Chemical Sensitivity, Gulf War Syndrome and Possibly Many Others" by Martin Pall in Townsend Letter
- 2009, Dr. Pall Debuts Website on 'Tenth-Paradigm' Diseases Including FM, ME/CFS, and MCS
- 2007, Nitric Oxide Cycle Theory: Will It Explain CFS, FM, and Other ‘Unexplained’ Illnesses? - Q&A with Martin L. Pall, PhD
Talks and interviews
- 2014, Martin Pall explains "Unexplained Illnesses" (English with French subtitles)
- 2007, "Live Chat with Martin L. Pall, PhD – July 6, 2007: Professor of Biochemistry Explains Mechanisms of Chronic Fatigue Syndrome and Fibromyalgia & Suggested Protocol"
- 2007, Speaker at the 2nd Invest in ME International ME Conference - Biochemical Underpinnings of ME/CFS - DVD available
Publications on ME/CFS
- 2011, Myalgic encephalomyelitis: International Consensus Criteria.
- 2011, Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue?
Summary: "Chronic NF-κB activation has been supposed as a key event in chronic fatigue syndrome (CFS) and many other better-defined pro-inflammatory diseases. Knowledge about the impact of deficiency vitamin D on chronic NF-κB activation could open a new disease approach. Whereas NF-κB activation leads at first to a pro-inflammatory immune response, later on a vitamin D-dependent anti-inflammatory response ensues. Binding of the active vitamin D metabolite 1,25(OH)2D3 to vitamin D receptor (VDR) yields a transcription factor which represses NF-κB activation, and additionally modulates and down-regulates adaptive, but enhances innate immune responses, and improves redox balance, thus counterbalancing inflammation on multiple levels. However, this built-in late counterbalance against inflammation works only when stores of calcium and 25(OH)D3 are abundant. Therefore a connection between lowered vitamin D-metabolism and persistent NF-κB activation, augmented nitrosative-oxidative stress, redox imbalance, chronic inflammation, and concomitant fatigue can be postulated. In order to confirm this hypothesis, randomized controlled clinical studies about the clinical effects of supplementation of calcium and vitamin D3 would be necessary in diseases characterized by persistent NF-κB activation and chronic inflammation and fatigue."
- 2008, Post-radiation syndrome as a NO/ONOO- cycle, chronic fatigue syndrome-like disease.
- 2005, Nitric oxide and the etiology of chronic fatigue syndrome: giving credit where credit is due.
- 2003, Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients.
- 2002, Levels of Nitric Oxide Synthase Product Citrulline Are Elevated in Sera of Chronic Fatigue Syndrome Patients
"Abstract - Serum levels of citrulline, a product of nitric oxide synthase activity, were measured in 36 CFS patients and 16 controls to determine whether synthase activity may be elevated in CFS patients. Serum citrulline levels were found to be significantly elevated in CFS patients and, in addition, there was a trend towards higher levels in CFS patients with stronger symptoms. These results provide support for the view that nitric oxide synthase activity tends to be elevated in CFS patients, thus supporting a prediction of the elevated nitric oxide/peroxynitrite theory of CFS etiology."
- 2002, Chronic fatigue syndrome/myalgic encephalitis.
- 2001, Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite.
- 2001, Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress disorder.
- 2000, Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome.
"ABSTRACT: The etiology of chronic fatigue syndrome (CFS) has been both obscure and highly contentious, leading to substantial barriers to both clear diagnosis and effective treatment. I propose here a novel hypothesis of CFS in which either viral or bacterial infection induces one or more cytokines, IL-1beta IL-6, TNF-alpha and IFN-gamma. These induce nitric oxide synthase (iNOS), leading to increased nitric oxide levels. Nitric oxide, in turn, reacts with superoxide radical to generate the potent oxidant peroxynitrite. Multiple amplification and positive feedback mechanisms are proposed by which once peroxynitrite levels are elevated, they tend to be sustained at a high level. This proposed mechanism may lower the HPA axis activity and be maintained by consequent lowered glucocorticoid levels. Similarities are discussed among CFS and autoimmune and other diseases previously shown to be associated with elevated peroxynitrite. Multiple pharmacological approaches to the treatment of CFS are suggested by this hypothesis."
- Elevated Peroxynitrite as the Cause of Chronic Fatigue Syndrome: Other Inducers and Mechanisms of Symptom Generation
"Abstract - In an earlier paper, I proposed that chronic fatigue syndrome (CFS) is caused by a response to infection, involving the induction of inflammatory cytokines which induce, in turn, the inducible nitric oxide synthase, producing elevated nitric oxide. Nitric oxide reacts with superoxide to form the potent oxidant, peroxynitrite. Six positive feedback loops were proposed by which peroxynitrite may stay elevated, acting to increase levels of both nitric oxide and superoxide, which react to form more peroxynitrite. This vicious cycle based on known biochemistry is proposed to be the central cause of CFS. The current paper discusses additional inducers which may act by increasing nitric oxide (physical or psychological trauma) or increasing superoxide (hypoxia) and the role of orthostatic intolerance, Ehlers-Danlos syndrome, excessive exercise, exercise intolerance and carbon monoxide in inducing hypoxia and consequently superoxide and peroxynitrite. The major symptoms of CFS can all be interpreted as relatively direct consequences of the pathophysiology predicted by the elevated peroxynitrite theory of CFS. Attractive mechanisms are proposed by which elevated peroxynitrite, nitric oxide and/or related physiological changes may induce CFS symptoms including fatigue, immune dysfunction, learning and memory dysfunction, multi-organ pain, exercise intoler-ance/postexertional malaise and orthostatic intolerance. Roles are discussed for six factors likely to influence the frequency of CFS induction in response to infection or other inducing events."
- 2000, Cobalamin Used in Chronic Fatigue Syndrome Therapy Is a Nitric Oxide Scavenger
"ABSTRACT: Cobalamin (vitamin B12) in the form of hydroxocobalamin or cyanocobalamin injections has been widely used to treat chronic fatigue syndrome (CFS). Hydroxocobalamin is a nitric oxide scavenger and is proposed here to act as such a scavenger in CFS treatment. Its possible efficacy in CFS treatment, if further substantiated, may provide confirmation of a prediction of the elevated nitric oxide/peroxynitrite theory of CFS etiology. This interpretation of the possible role of cobalamin in CFS treatment suggests a useful perspective for confirming and optimizing this treatment."
- Carruthers, BM; van de Sande, MI; De Meirleir, KL; Klimas, NG; Broderick, G; Mitchell, T; Staines, D; Powles, A C P; Speight, N; Vallings, R; Bateman, L; Baumgarten-Austrheim, B; Bell, DS; Carlo-Stella, N; Chia, J; Darragh, A; Jo, D; Lewis, D; Light, A; Marshall-Gradisnik, S; Mena, I; Mikovits, JA; Miwa, K; Murovska, M; Pall, ML; Stevens, S (2011), "Myalgic encephalomyelitis: International Consensus Criteria.", Journal of Internal Medicine, 270 (4): 327-38, PMID 21777306, doi:10.1111/j.1365-2796.2011.02428.x
- Pall, Matin L. (2007), Explaining 'Unexplained Illnesses': Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, and Gulf War Syndrome (book), ISBN 978-0789023889
- Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AC, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S. (2011). Myalgic encephalomyelitis: International Consensus Criteria. Journal of Internal Medicine, 270 (4):327-38. doi: 10.1111/j.1365-2796.2011.02428.x. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21777306
- Höck, Anna Dorothea; Pall, Martin L. (2011), "Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue?", Medical Hypotheses, 76 (2): 208-13, PMID 20980105, doi:10.1016/j.mehy.2010.09.032
- Pall, ML. (2008). Post-radiation syndrome as a NO/ONOO- cycle, chronic fatigue syndrome-like disease. Medical Hypotheses, 71 (4):537-41. doi:10.1016/j.mehy.2008.05.023. Epub 2008 Jul 29. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18667279
- Pall ML. (2005). Nitric oxide and the etiology of chronic fatigue syndrome: giving credit where credit is due. Medical Hypotheses, 65 (3):631-3. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15936892.
- Smirnova IV, Pall ML. (2003). Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients. Molecular and Cellular Biochemistry, 248 (1-2):93-5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12870659
- Martin L. Pall. (2002). Levels of Nitric Oxide Synthase Product Citrulline Are Elevated in Sera of Chronic Fatigue Syndrome Patients. Journal of Chronic Fatigue Syndrome, Vol. 10, Iss. 2, pp. 37-41. http://dx.doi.org/10.1300/J092v10n03_04
- Pall, ML. (2002). Chronic fatigue syndrome/myalgic encephalitis. British Journal of General Practice, 52 (482):762. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12236283.
- Pall, ML. (2001). Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite. Medical Hypotheses, 57 (2):139-45. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11461161
- Pall ML, Satterlee JD. (2001). Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress disorder. Annals of the New York Academy of Science, 933.323-9. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12000033
- Pall, Martin (2000), "Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome", Medical Hypotheses, 54 (1): 115-125, PMID 10790736, doi:10.1054/mehy.1998.0825
- Martin L. Pall. (2000). Differential Diagnosis: The Challenge of Chronic Fatigue, Vol. 7, Iss. 4, pp. 45-58. http://dx.doi.org/10.1300/J092v07n04_05
- Pall, Martin (2000), "Cobalamin Used in Chronic Fatigue Syndrome Therapy Is a Nitric Oxide Scavenger", Journal of Chronic Fatigue Syndrome, 8 (2): 39-44, doi:10.1300/J092v08n02_04