Assuming this is the main lead, wouldn't the tryptophan levels be too high in CFS/ME patients? Or wouldn't Niacin supplementation or another NAD+ booster help? Not in my case. My intracellular tryptophan levels were even a bit low.
Here is my opinion. This research is focused on the manifestation pathway of CFS/ME but not on the causality.
Genetics could be a causality. But there is nothing special in my IDO1
gene. No loss of function, major deletion, or rare mutation at least.
Given the assumption that EBV is the major cause of EBV and that it is immunologically mediated, you can find evidence of EBV involvement in the IDO1 pathway. EBV-mutated B cells could produce EBV-IDO which competes with human IDO (10.1016/j.imlet.2011.01.009
). Maybe EBV-IDO even has a greater affinity than human IDO and thereby enhancing its relative concentration factor. Maybe EBV-IDO is not as functional in the Tryptophan metabolism as human IDO but it seems to be functional in suppressing L-kynurenine signaling and thereby evade immune recognition (10.1016/j.imlet.2011.01.009
). I've pointed out similar observations with EBV-IL-10 vs. human IL-10.
This is from another study (10.1128/JVI.03678-13
) on EBV-IDO and I see similarities with the pathology of CFS/ME.
- CFS/ME is associated with a suppressed cytotoxic activity of CD8+ T cells (Selin et Gil).
- CFS/ME is associated with a decrease in CD8+ T cell ratio, indicating a problem with the proliferation or maturation of CD8+ T cells (Selin et Gil).
- CFS/ME is associated with an increase in Foxp3+Helios+ T/-reg cells (Selin et Gil). IDO signaling is known to induce this conversion to Foxp3+ Tregs (10.3892/mmr.2018.8537).
- CFS/ME is associated with elevated NF-κB (10.1016/j.mehy.2012.07.034).
- CFS/ME is associated with enhanced IL-17/Th17 signaling (Selin et Gil). EBV-induced EGR1/p38/MAPK/IL-17 signaling is speculated to be the reason (10.3390/biom10111484).
Another thing to consider. Many CFS/ME patients who report remission, within a few days report a relapse. I recently experienced this myself. Given the assumption that the IDO1 function is the explanation for the major CFS/ME symptoms, why do you have such a fast and immediate relapse? Something must push you back into the metabolic trap and whatever it is, it seems to adapt to the metabolic conditions given by the approached therapy. This also supports my theory that there is an active pathology behind the metabolic trap and this pathology won't disappear by trying to fix the trap only.