LC, POTS, and ME/CFS: Lifting the Fog

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine (Hcy) is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, gamma aminobutyric acid (GABA), and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and varicella zoster virus (VZV), due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by Hcy, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.