Okay so i'm super confused. I thought mTOR was believed to be under-activated in ME/CFS patients and from memory Davis said in his video NOT to inhibit it...but according to
this, inhibiting mTOR does the following:
I realise that the context is different (Leukemic cells), but isn't this what we want and perhaps why Rapamune/Sirolimus helps?
Nandixon beat me to some parts. But there are a lot of nuances. To say anything right now, I have to put aside the fact it's cancer cells, sub-cellular localization of mTor, and relative concentration of the mTor enzyme (cause it's rarely all or nothing). Already a lot of variables, not all of which I grasp, but anyway...
The confusing factor is that mTorC1 itself does in fact increase oxidative phosphorylation in mitos. That comes off counter to the Akt-producer/mTorC1-consumer bastardization from other articles. But in reality a lot of the oxphos from mTorC1 is just there to fuel protein synthesis and proliferation. So it's not free energy, it gets used up simultaneously, and depending how measured it gives different net effect (I was still trying to wrap my head around some of that, so I'll get back to you someday...).
In the case of CFS/ME, since PDH is already ruined, I'd think lowering mTorC1 in those cells
might simply make no significant difference to oxphos from glycolysis. But meanwhile knocking down mTorC1 still lowers the energy-consuming processes. Such that relative to disease, keeping your fuel intake the same, Akt+/mTorC1- still increases net ATP [and through glycolysis].
[You can stick to simpler explanation along what nandixon wrote and say mTorC1 was simply too low such that lowering it makes no difference, while increase in Akt is pure positive... anything along these lines will work out]
I think the story probably doesn't end there, even for healthy people, but that gives another picture.
On related topic, for what it's worth, I was coming to the conclusion that the Akt might not have enough direct effects on PDH/PDK to explain
all the relief, it's depending on what is keeping PDK high, and there are other complications. So, while I'm personally convinced the Akt/mTor direct energy partitioning modulation is significant to maintaining energy high while on rapamycin and alternatives, the specific disease-modifying aspect - or multiple aspects - might likely be something else, immune suppression or other.
About alcohol, I've been coming across so many different possible explanations that it practically fits every theory. I'm not putting stock in it anymore.