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Chronic fatigue Syndrome (CFS): An objective metabolic disorder that affects at least seven body systems. Applications to manual therapy.

More than 2 million people in the United States have Chronic Fatigue Syndrome (CFS). CFS is a disease difficult to diagnose or treat. RK Naviaux published a ground-breaking study on CFS (1). He discovered a chemical signature showing that CFS is an objective metabolic disorder that affects at least seven systems (including mitochondrial energy metabolism, immune function, GI function, the microbiome, the autonomic nervous system, neuroendocrine, and brain functions).

The main discoveries of Robert Naviaux, PhD in virology and human genetics, is that CFS patients showed abnormalities in 20 metabolic pathways. 80% of the diagnostic metabolites were decreased. This is consistent with a hypometabolic syndrome, a hypometabolic strategy for the body, similar to a situation that permits survival and persistence under conditions of environmental stress.

For Robert Naviaux the brain controls the body metabolism. “Any factor that causes a chronic change in how the brain works will produce objective chemical changes in the blood. Reciprocally, any chronic change in any of the 7 systems…will produce compensatory chemical changes in the blood that are coordinated by the brain, but can also change brain function.

Mitochondria (the little powerhouse of the cell) lie at the center of cellular metabolism, coordinating over 500 different chemical reactions. To simplify, mitochondria have two main jobs in the cell: energy metabolism and cellular defense.

For Naviaux, all complex chronic disease as being the result of either mitochondrial hypermetabolism (underfunction) or mitochondrial hypometabolism (overfunction).

A lot of these reactions, for the students that took the brain class, is controlled at the level of the brain, especially the brainstem. “Beginning in the first trimester, the brainstem is responsible for the chemosensory integration of whole body metabolism.”

CFS, also called ME (Myalgic Encephalomyelitis) is related to a hypometabolic process called “dauer”. Benjamin Lant and Kenneth B. Storey (2) describe: “Entry into a hypometabolic state, where metabolic rate is strongly suppressed and normal activities are suspended, is actually a widespread response to stress across phylogeny providing organisms with a greater chance to survive through stressful times. As an example, entry into a dormant state where metabolic rate falls to just 10% of normal resting rate provides an automatic 10-fold extension of the time that organisms can survive using only stored endogenous fuel reserves to support their energy needs. Such a time extension is typically more than enough to ensure survival through predictable seasonal periods of environmental stress…A hypometabolic state where metabolic rate is typically suppressed by at least 70% and in many cases to >95% or greater is a critical part of phenomena including winter hibernation by mammals, nightly torpor by small birds and mammals…under summer drought conditions, anaerobiosis in response to oxygen depletion, cold-hardiness and many other forms of dormancy or diapause…

Just to go over some of his concepts. Naviaux take the example of the cell danger response (which not the same process of hypometabolism involved in CFS/ME).

He explains: “The cell danger response (CDR) is a…cellular metabolic response that is activated when a cell encounters a chemical, physical, or microbial threat that could injure or kill the cell. Common microbial threats are viruses, bacteria, fungi, and parasites. Physical threats include heat, salt, or pH shock, or UV or ionizing radiation. Chemical forms of danger include heavy and trace metals like lead, mercury, cadmium, arsenic, and nickel, certain electrophilic aromatic chemicals like the plasticizer bisphenol A, the chemical flame retardants like the brominated diphenyl ethers (BDEs), and certain halogenated pesticides like chlorpyrifos and DDT. Psychological trauma, particularly during childhood, can also activate the cell danger response, produce chronic inflammation, and increase the risk of many disorders...Mitochondria are evolved to sense all of these threats according to the induced changes in electron flow available for normal metabolism. The cell danger response is coordinated in the brain via chemosensory integration of whole body and microbiome metabolism. Abnormal persistence of the CDR ultimately leads to altered organ function and behavior, and results in chronic disease.

…The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm…after the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results.”
When the CDR fails to resolve, chronic disease results.
CFS/ME may be a hypometabolic process that took place after a phase of chronic neuroinflammation.

In conclusion: A new study showing that CFS is a specific disease with very consistent biomarkers. If affects at least seven body systems including immune function, mitochondria, the microbiome, the ANS, neuroendocrine and brain functions. It may explain why we use many brain techniques to help alleviate CFS/ME (as well as fibromyalgia), including to a great extent releasing the brainstem, that has shown to present abnormalities in these conditions (4, 5).

(1) Naviaux RK et al. Metabolic features of chronic fatigue syndrome.
(2) Lant B, Storey KB. An Overview of Stress Response and Hypometabolic Strategies in Caenorhabditis elegans: Conserved and Contrasting Signals with the Mammalian System. Int J Biol Sci. 2010; 6(1): 9–50. PMCID: PMC2808051.
(3) Naviaux RK. Metabolic features of the cell danger response. Mitochondrion. 2014 May;16:7-17.
(4) Barnden LR, Kwiatek R, Crouch B, Burnet R, Del Fante. Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome. Neuroimage Clin. 2016 Mar 31;11:530-7. doi: 10.1016/j.nicl.2016.03.017. eCollection 2016.
(5) Barnden, L. R., Crouch B, Kwiatek R, R. et al. 2011. A brain MRI study of chronic fatigue syndrome: Evidence of brainstem dysfunction and altered homeostasis. NMR in Biomedicine 24(10):1302-1312.




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