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Chronic Fatigue Syndrome is a physiological state in which the patient feels high levels of fatigue without an obvious organic cause, which affects around 1 in 400 people in the developed world.
A wide range of causes have been suggested, including immune or hormonal dysfunction, viral or bacterial infection, and psychological somatization.
It is likely that several causes are needed to trigger the disease, and that the triggers are different from the mechanisms that maintain fatigue over months or years. Many treatments have been tested for CFS, with very limited success – a program of combined CBT and graded exercise shows the most effect.
I suggest that patients with CFS have a reduced ability to increase mitochondrial energy production [mitochondria are tiny energy generators in each cell] when exertion requires it, with fewer mitochondria that are each more efficient, and hence nearer to their maximum energy output, than normal.
A range of indirect evidence suggests that the renin-angiotensin system [RAS] stimulates mitochondrial responsiveness and reduces mitochondrial efficiency: Chronic under-stimulation of this system could contribute to CFS etiology. [Renin, an enzyme produced in the kidney, acts on angiotensinogen produced by the liver to form angiotensin. Angiotensin causes blood vessels to constrict/raises blood pressure.]
If correct, this means that CFS can be successfully treated with RAS agonists (e.g., angiotensin mimetics), or adrenergic agonists. It also suggests that there will be a positive link between the use of adrenergic- and RAS-blocking drugs and CFS incidence, and a negative link between adrenergic agonist use and CFS. [An RAS agonist or mimic would stimulate renin-angiotensin system activity. A blocker would reduce it.]