Itaconate Trap Study

One of the key metabolic theses aiming to explain ME/CFS symptoms is the dysregulated nitrogen metabolism theory proposed by Armstrong and colleagues. Three features of this theory make it attractive:

1) it is consistent with the observed shift from carbohydrate to alternative sources of energy (amino acids and fatty acids),

2) it predicts a reduction in oxygen consumption consistent with a hypometabolic state, and

3) it predicts overproduction of ammonia, a known neurotoxin that could explain ME/CFS neurological symptoms. One underdeveloped aspect of the nitrogen metabolism theory of ME/CFS is the mechanistic chain of events connecting the initial infectious or traumatic trigger to a chronically altered state of central carbon and mitochondrial metabolism.

This computational proposal aims to fill that gap by testing mechanisms that have the potential for switch-like or bistable behavior.