Simmaron Research blog post, by Cort Johnson, 1 January 2018: Could Chronic Fatigue Syndrome (ME/CFS) Be a Chronic Form of Sepsis?

“In this monograph I would like to explore the concept of neuro-immune fatigue as a metabolic illness resulting from a series of events beginning with an infection, toxic exposure or neurologic injury.” Dr. David Bell, 2007

This is one of a series of blogs highlighting hypotheses mostly written by doctors or other professionals with ME/CFS, or in this case, doctors who have cared for them. The hypothesis examined in this case: Dr. Bell’s idea, produced in his monograph, “Cellular Hypoxia and Neuro-immune Fatigue”, that chronic fatigue syndrome (ME/CFS) could be a kind of “slow sepsis”.

Bell’s “Cellular Hypoxia” book was published in 2007, long before he was probably acquainted with Dr. Naviaux’s and others’ work and before the recent explosion of interest in cellular energy production in ME/CFS. Naviaux and others would probably smile, though, at Bell’s prediction that with ME/CFS and other diseases, “we may be witnessing the emergence of the next era of medicine: the diagnosis and treatment of cellular metabolic diseases”.

Sepsis is a life-threatening response to infection or trauma that can lead to tissue damage, organ failure, and death. In some ways, sepsis sounds similar to autoimmunity. For reasons the medical profession does not understand, sepsis begins when the immune system resets itself, stops fighting pathogens, and turns on the body.

The results are often devastating. The near complete body breakdown that results makes sepsis the most expensive disease hospitals treat.  Forty percent of patients with severe sepsis do not survive.

Chronic Fatigue Syndrome (ME/CFS) – A Mild but Chronic State of Septic Shock?

ME/CFS is obviously not sepsis, but it does share some interesting characteristics.  With his “cellular hypoxia” monograph published in 2007, Dr. David Bell suggested that people with ME/CFS may exist in a “mild, but chronic state of septic shock”. Bell came to this conclusion after finding that sepsis and ME/CFS produces what he believed is a similar kind of oxygen dysfunction. In sepsis and in ME/CFS, Dr. Bell notes that oxygen is actually abundant: it’s abundant in the air, the lungs and the blood of ME/CFS patients, but it’s just not getting taken up by the tissues.

Bell reports that in septic shock, the following events occur (note the last one):

• a serious infection occurs which –
• results in the production of cytokines which –
• increases nitric oxide levels which then –
• interfere with the production of cellular energy.

Bell noted that when nitric oxide blocks the flow of oxygen in severe septic shock, a patient can still die despite doctors giving him/her as much blood and oxygen as they need.

Bell suggests a similar process to sepsis occurs more gradually in ME/CFS. First, an initiating infection or toxic exposure triggers the immune system to produce pro-inflammatory cytokines and nitric oxide (NO). From there, NO increases peroxynitrite and superoxide (Martin Pall’s hypothesis), which causes oxidative stress and interferes with mitochondrial function.

Ultimately, the cell becomes hypoxic (oxygen-starved), and neuropathies and autoimmune and other problems develop.

The idea that impaired oxygen intake might be limiting energy production has gained some currency since Bell wrote his monograph.  Vermoulen’s exercise studies suggest that impaired oxygen intake, not mitochondrial problems, is the key issue in energy generation. The early stages of Ron Davis’s collaboration with an San Jose State University bio-engineer suggest that the red blood cells may have difficulty getting to the tissues. Other researchers have found autoantibodies to receptors that open and close the blood vessels in a subset of ME/CFS patients.

Last year, Chris Armstrong in, The “Starvation” Disease? Metabolomics Meets Chronic Fatigue Syndrome Down Under“, took the sepsis/ME/CFS notion one step further when he noted that many of the metabolomic anomalies (reduced amino acids, reduced lipids and increased glucose levels) found in ME/CFS are also found in sepsis and starvation.

Remarking that during sepsis, immune cells rely entirely on glycolysis to proliferate, Armstrong speculated, much as Bell did years earlier, that an infection or autoimmune process might have triggered a sepsis-like condition which lead to a state of chronic metabolic starvation.

A last tie to sepsis is an incidental one.  Ron Davis and Ron Tompkins of the Open Medicine Foundation worked on sepsis together. Based on his work there, Davis has said ME/CFS could be a kind of atypical sepsis.

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