Ron Davis Update

Janet Dafoe

Board Member

1) will the test of the FDA drugs be published eventually? if so, is that in the works? time line?

2) chinese traditional herbs: are they still going to also be examined and if so, when might that occur?
Yes, the plan is to publish this work. At the moment they are focusing on the FDA drugs and the Chinese herbs are a fall back in case they can’t make those work.

Janet Dafoe

Board Member
I have no issues with the OMF research at Stanford. I support it.

I wish I could understand how an actual drug could become available to us for treatments. The process is very unclear to me, but thats my problem not theirs.

Same with one or more diagnostics. How exactly something becomes diagnostic, is very unclear to me.
Diagnostics: first you have to do enough tests to demonstrate that it’s reliable in discriminating between MECFS patients and others.
Then you submit this data to the FDA with a request for it to become an approved diagnostic test.
If it’s approved, then the only labs that can do it are CLIA certified labs.

Drugs: after some FDA approved drugs have been tested enough that the researchers feel it may be helping and not having bad side effects, then it will be announced and it would be up to doctors to figure out whether to prescribe it off label. In order for it to be prescribed on label, it needs to be FDA approved as a drug for MECFS. When that happens insurance companies would cover it.


Senior Member
@Janet Dafoe so are you guys going to share some (eg the safest 10 or something.?) drug names for us to try with our doctors etc?

It is a little unclear to me from @BrightCandle's notes - it sounds like you are planning to release some based on what he wrote, but I was not being quite so optimistic as to bet on that happening this early..


Senior Member
I had a chance to listen to some excellent teachings from the PhDs about the Itaconate Pathway. For what it is worth, I thought I would break it down into simpler terms.

1/ The body produces energy through a complex biochemical process. This is also known as the Kreb's Cycle. Again, this is a very complex cycle that involves a number of raw materials to function.

2/ When this cycle is interrupted then cells cannot be efficient in performing their duties.

3/ When the cells cannot manufacture energy, then problems arise. For instance, immune cells use this cycle (as do neurological cells, skin cells etc). If the immune cells are not functioning correctly because the complex metabolic cycles are broken, then your immune system will not be robust. Copy and paste this same concept to the other cells of the body (neurological, detoxification etc.)

4/ The Itaconate Pathway is switched on by Immune activation.

5/ It is the Itaconate Pathway that disrupts the Kreb's Cycle.

6/ If the Kreb's Cycle is interrupted, then all kinds of wonky things* happen. Example, I see some pronounced cycles that occur, then disappear then reappear such as sleep (quality), circadian rhythms, energy production etc. These are from disruptive changes in the system due to some "event". The body learns this pattern then make changes to return to center.

* "wonky things" is not a scientific term :>)


Senior Member
The obvious solution to the problem is to eliminate the bug(s) that are stimulating the immune system or #2, use supportive therapies to help modulate the body. Obviously, the first solution is preferable.


Senior Member
Let's face it. We have been trying everything on ourselves by ourselves for a long long time. Every now and then a doctor pops up who won't lose their medical license for trying to help.. Such as the story told by Sara in another thread about her husband Jonas. They are in Sweden I think. That doctor accepted that 'do no harm' means 'don't wait.' That being said, I understand why no one wants to be held responsible for our experiments. The good thing about what may be published is that the field is research - not medical practice. No harm in that. We're adults. Children are a different story.


Senior Member
Oh dear...look at the price for the hair tests. Hopefully some people have some money to do it.


The good news is patients don't die the bad news..
If he's right I wonder if taking acetyl coA would give us a bit more energy. He mentions it can be bought as a supplement...I don't feel I know enough yet to try it.
Would a viral, bacterial or fungal reservoir potentially keep the shunt on? Surely in those cells only though. Could there be a cell-danger response like reaction of cells elsewhere that initiate the shunt to protect themselves? I look forward to next week's video to learn more.

Ben H

OMF Volunteer Correspondent
If you're unable to view on Twitter, here is the contents of the tweets:

Itaconate shunt

ME/CFS hypothesis by @RDPhair, Ron Davis and @C_W_Armstrong.

Based on a proposal of bistability/on-off switches in amino acid metabolism. Prior research by Chris Armstrong showing ME/CFS patient's metabolism preferentially favouring amino-acids over glucose and fatty acids.

What could cause this change-the burning of amino acids instead of sugar?

What makes this state chronic?

*Diagram of the Krebs cycle/TCA showing related metabolism*

Importance of overall diagram:

In basic-fuels comes in, ATP comes out. ATP is the energy currency of the cell. Used to do all work cells must do (pump ions across membranes, synthesise proteins).

*The Itaconate shunt pathway is added to diagram*.

Not normally operating in mitochondria.

Initiated by innate immune system.

It is 'shunting' away metabolism significantly from the normal Krebs cycle processes that rely on sugars, fatty acids and amino acids.

Why would the body want to do this?

To prevent energy for the virus/bacterial infection for long enough to hand off responsibility to the adaptive immune system.

Mechanism for slowing the ability of viruses/bacteria to replicate inside the cell.

Hypothesis is that this Itaconate shunt pathway is on chronically in ME/CFS patients. It's been turned on but not been turned off.

This sequesters coA molecule away from reactions needed for normal metabolism-slows glycolysis, beta-oxidation and BCAA's entering Krebs cycle.

Nowhere to go (metabolically)!

*GABA shunt diagram shown*

This is where the 'GABA shunt' pathway comes into play. Glutamate (and transaminated amino acids) can enter via 2-OG. Glutamate can convert to GABA in this pathway.

Can partially compensate-calculated at about 43% efficiency compared to normal Krebs cycle. Can still create NADH to be used by the ETC (electron transport chain) to create ATP. So some ATP is still created.

However this lack of energy only the tip of the 'problem iceberg'!

An example of this problem-the brain.

The brain with the rewired Krebs cycle/GABA shunt will now be using the glutamate + GABA mentioned above to make energy.

This is an issue because you are burning your neurotransmitters for energy (!) as is the only way to make ATP.

Hypothesises this will cause brain fog.

Thinks this pathway can explain PEM because a byproduct of ATP usage and physical activity is a conversion to ADP. In the process of this happening, ammonia is produced.

Ammonia is a known neurotoxin.

It's a hypothesis, needs testing.

What makes (the Itaconate shunt) chronic? That is the topic of the next video.

Research funded by Vinod Khosla's Amar foundation.

Hope that helps. The video is well, well worth checking out, it goes into far more detail and is beautiful biochemically! Though I realise many are unable/struggle cognitively so the above is a condensed alternative.

Hope it helps,