Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Long COVID.

Itaconate Trap Study

This project aims to look at metabolic traps in central carbon metabolism that lead to observed altered energy production pathways in ME/CFS.

  • Christopher Armstrong, PhD

  • Rob Phair, PhD

  • Constructed the differential equation model for the TCA cycle.
  • Developed the itaconate trap hypothesis by looking for mechanisms that prioritise the use of amino acids for energy production.
  • Itaconate cycle can be initiated by pathogens specifically via innate immune signals (IFN-alpha).
  • Currently exploring the relationship between IFN-alpha, itaconate, cellular metabolism, and ME/CFS.

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.


  • Explore the itaconate trap and other potential traps in central carbon metabolism.
  • Build pathways of central carbon metabolism.
  • Develop kinetic models to try predict potential “weakness” points.
  • Test the hypothesis experimentally.