Dr. Ronald W. Davis Answers Patient Questions: Q and A follow-up to 2/21/17 Research Update

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Aroa

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Could anyone please post a reliable list of substances that may inhibit mTOR and if possible which of them would have a major impact ?
 
nandixon

nandixon

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Murph said:
I see from the link above that mTOR is big.

"Both mTOR complexes are large, with mTORC1 having six and mTORC2 seven known protein components."

(unfortunately Ron's 'filtering solves the problem' finding does not seem to fit with @nandixon's mTor inihibition theory! That would've been neat.)
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Everything still fits! The main thing that I’d originally observed is that the Fluge & Mella study results appeared to show that the mTORC1 pathway leading to the PDH complex is under-activated or inhibited in ME/CFS, which is consistent with the involvement of mTOR that Dr Davis said in the video he'd already discovered is likely present. (This is a nice cross-confirmation between Dr Davis’s and Fluge & Mella’s work!)

Therefore, the filtering of the blood that appears to fix things could, for example, simply be removing an autoantibody or blocking agent directed against mTOR (or another component of the mTORC1 complex) or in fact one directed against any component in the multiple upstream pathways leading to mTOR/mTORC1 (e.g., ones running through Akt or Erk, etc).

The Naviaux study additionally showed that sphingolipids (e.g., ceramides) are low in ME/CFS. The Fluge & Mella and Naviaux studies can fit together in at least two different ways, one in which the low ceramides are upstream of the inhibited PDH and the other in which they're downstream, and both possibilities are still perfectly viable.

In simple graphical terms, the two possibilities (assuming there is in fact a causal relationship between the inhibited PDH and the low ceramides) are:

1. ???--> Low ceramides--> Low S1P--> [S1PR1]--> Under-activated Akt/mTOR (mTORC1)--> Inhibited PDH complex

2. ???--> Under-activated Akt/mTOR (mTORC1)--> Inhibited PDH complex--> Low acetyl-CoA--> [Low palmitoyl-CoA]--> Low ceramides--> Low S1P

(An inhibited PDH causes energy impairment while impaired S1P signaling causes endothelial dysfunction and blood pressure/volume regulation problems; S1P = sphingosine-1-phosphate.)

Option #2 might be more preferred now that Dr Davis has indicated that there seems to be something present in ME/CFS blood that shouldn't be there. (Although I think he said in the video that he couldn't rule out a lack of something. Note that filtering out one thing could make something else that's lacking more effective.)
 
slysaint

slysaint

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eljefe19 said:
mTOR inhibitors and activators in this article.
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Valentijn said:
The list comes from selfhacked, which isn't a particularly reputable site and is heavily associated with the heal-thyself brigade and related spam about various natural remedies. The (R)s link to research, which would need to be carefully read before assuming the listed summary is correct.
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JES

JES

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slysaint said:
This is a rather simplistic question but, if it's an on/off switch scenario why are some more severely affected than others?
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One reason could lie in differences in the ways that our bodies tries to compensate for this problem. According to Fluge and Mella, men and women were observed to have very distinct differences in some key aspects. If I remember correctly, women in their study had massively depleted amino acid levels, whereas men with the disease were much closer to normal. One explanation to this was that men tend to have more muscle mass and can use proteins from their muscle tissue as an energy reserve/source.
 
Daisymay

Daisymay

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slysaint said:
This is a rather simplistic question but, if it's an on/off switch scenario why are some more severely affected than others?
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Just a guess, that is may be partly down to our individual genetics/epigenetics and how that interplays with the disease.

So if my memory serves me correctly, about 75% of the metabolic problems they were finding, were common to all ME patients, but 25% of the problems were down to people's individual genetics. Add those two together and you get the commonality of symptoms plus the differences between us all.

And I guess the different initial causes, differing infections, environmental exposures, diet, those who were told to initially push on, exercise etc all of these sorts of differences, put it all together hence some are more severely affected than others
 
S

Sasha

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dannybex

dannybex

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sue la-la said:
the full transcript is now available. :)

https://www.dropbox.com/s/fh8c5bgezksi5f2/20170308 - Ron Davis - transcript of video Q&A - v0.2.pdf?dl=0
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Thanks Sue. There's was some question earlier in the thread as to whether Dr. Davis is saying "we've tested all FDA drugs in use"...or "in yeast". This is at 12:13 in the video. It's hard to tell, but it does sound more like the latter.

Editing to flag @sue la-la. It should indeed be "all FDA drugs in yeast", as you'll see the next sentence talks about yeast.
 
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P

perrier

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A.B. said:
They need 5$ million a year for several years. :(

Patient donations aren't going to be enough. And the NIH isn't providing enough funding. What should we do? Lobby for specific funding for this project? Go begging to billionaire philantropists?[/
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