ME/CFS Research Roundup: Brief highlights of biomedical research to date
DISABILITY & QUALITY OF LIFE
People with ME/CFS score lower on measures of physical function and overall quality of life than most other chronic disease groups, including MS, cancer and stroke, and the experience of patients with severe ME/CFS is comparable to end stage HIV or heart failure (
Nacul 2011,
Falik Hvidberg 2015).
METABOLIC DYSFUNCTION
Observed modifications in the status of cellular metabolism genes (
deVega 2017,
Billing-Ross 2016) and analysis of metabolites and proteins in the blood have shown marked abnormalities in metabolic pathways (
Germain 2017,
Naviaux 2016,
Armstrong 2012), demonstrating that basic energy production mechanisms are dysfunctional and, thus, ME/CFS patients exist in a persistent state of energetic conservation at the cellular level.
A more extensive exploration of this phenomenon specifically identified impaired function of a protein called pyruvate dehydrogenase, a critical enzyme in the pathway that generates ATP, the body’s energy currency (
Fluge 2016). For every 28 ATP molecules generated via aerobic metabolism in a healthy person, only 2 ATP are produced by a ME/CFS’s patient’s mitochondria via anaerobic processes, meaning their energy budget for all survival functions is drastically reduced, consistent with patients’ reported experience of profound and unrelenting fatigue.
Collectively, these studies demonstrate that the quantity of physical energy available for cellular functions is severely restricted in ME/CFS patients and their cells are forced to convert to a less efficient mode of energy production, though the root cause of this impairment has not been identified (
Morris 2014).
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POST-EXERTIONAL MALAISE
The hallmark feature defining ME/CFS is the experience of worsening of all symptoms [fatigue, feeling “unwell” (malaise), cognitive impairment, sensory hypersensitivity, pain, etc.] following physical or cognitive exertion, often at extremely minimal thresholds of activity (
VanNess 2010). This is known as post-exertional malaise (PEM) and distinguishes ME/CFS from confounding disorders, such as depression, where patients conversely feel better after exertion. Carefully constructed studies of ME/CFS patients’ physiologic response to exertion at several time intervals have revealed objective biologic measures of oxygen utilization which pinpoint the metabolic switch from aerobic to anaerobic metabolism (
Snell 2013,
Keller 2014), corroborating patients’ reported PEM symptoms and other researchers’ findings of metabolic dysfunction.
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here.
NEUROLOGIC INFLAMMATION
A sizable and longstanding body of evidence from imaging studies demonstrates abnormalities in the central nervous systems of ME/CFS patients. Several brain MRI analyses have shown reduced white and gray matter volumes indicating long-term damage to neurologic tissues, a finding which is consistent with the poor memory and cognitive impairment experienced by patients (
Finkelmeyer 2017,
Shan 2016,
Barnden 2011,
Zeineh 2015,
Puri 2012,
Lange 1999).
More specifically, PET scans of ME/CFS patient brains showed evidence of neuroinflammation indicated by an elevated presence of activated microglial cells, and these levels correlated with the severity of cognitive impairment and pain (
Nakatomi 2014). This finding is consistent with reports that some glial cell inhibitors can improve patients’ condition (
Younger 2014).
The vagus nerve, which travels from the brainstem through the abdomen and interfaces with many major organ systems, delivers the “rest and digest” signal from the parasympathetic nervous system as an antidote to the activated “fight or flight” state induced by the sympathetic nervous system. Dysfunction in these processes is thought to be at the root of symptoms such as heart rate variability, sleep disturbance and orthostatic intolerance experienced in ME/CFS (
Morris 2013), and this has been recently postulated to be caused impaired function of the vagus nerve, possibly due to direct vagal nerve infection (
VanElzakker 2013).
