The itaconate shunt hypothesis
- Thread starter Jaybee00
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I agree, it's a nice presentation and the idea is appealing in many ways.
Towards the end there are some hypotheses of what should be able to be found if the idea is true. Robert says that a number of the hypotheses have already been found to be correct - it would be good to have a good look at those.
I'm glad Robert's team continues to work on the idea.
Towards the end there are some hypotheses of what should be able to be found if the idea is true. Robert says that a number of the hypotheses have already been found to be correct - it would be good to have a good look at those.
I'm glad Robert's team continues to work on the idea.
Many of us can't see Twitter threads.
Can someone say whether this is just chat or has some valid scientific content?
Jonathan Edwards
Senior Member (Voting Rights)
I thought even Robert had given up the metabolic trap idea.
Mij
Senior Member (Voting Rights)
There are 24 tweets following his original. He goes on to explain the "tryptophan metabolism" theory and the "trap hypothesis".
Have the studies cited here been discussed before – and have they been validated or rejected?
If you replace the x.com in the URL with nitter.net you'll be able to read the thread.
Jonathan Edwards
Senior Member (Voting Rights)
We had quite. lengthy discussion with Robert in a thread here. The itaconate idea is intriguing and the implication of alpha interferon makes some sense. However, inasmuch as it has been tested I think the results for the interferon were negative. That does not kill the theory but I don't think we have any strong evidence in favour of it.
Were there any ideas as to what scientists could test to prove or disprove the hypothesis?
Jonathan Edwards
Senior Member (Voting Rights)
Further tests ? I think you would have to ask Robert. I forget.
wigglethemouse
Senior Member (Voting Rights)
Sjoerd Beentjes, PhD, University of Edinburgh presented "Seven replicated genomic associations of ME/CFS: A biobank study" at the Stanford ME/CFS community symposium on 11 Sept 2026. He only presented one of the 7 genes by name which turned out to be CLYBL which Robert Phair also discussed today again as a part of the Itaconate shunt hypothesis talk.
DMissa
Senior Member (Voting Rights)
which talk? it would be good to see the current version of rob's ideas
wigglethemouse
Senior Member (Voting Rights)
Last years talk is here
And a support talk also from last year about a zebra fish model here
This years talk was at the Stanford Symposium 11 Sept 2026 and should be posted to the same YouTube channel.
Link to a copy of the slides is in this post (hosted on google share drive)
This was a key slide showing separation between 10 patients and 10 controls.
DMissa
Senior Member (Voting Rights)
I am watching the talk. The pictured experiment was done using mixed PBMC by the sound of it. If so, these observations cannot be attributed directly to mitochondrial or metabolic differences because differences in the composition of those mixed PBMC will confound these measurements (different types of cells comprising mixed PBMC can have very different metabolic states and preferences to each other). The proportions of these different cell types naturally shift between individuals and even within individuals depending on many common factors. Greatly so.
This is the same confounder plaguing all of the PBMC seahorse work or that recent Long COVID PBMC omics paper that made the claim of mitochondrial problems.
The model is interesting and of course is very well thought out by Rob (especially the estrogen link) but I remain unaware of reliable evidence supporting the suspected mitochondrial issues. This needs to be tested in a homogeneous and comparable sample type. This can easily be done - this experiment is extremely cheap and easy. Put some cells into a few hundred bucks worth of biolog plates with some dye and press a button on a plate reader. You just need the cells to not have this confounding factor present. Well-sorted PBMC would be a good start since the question revolves around immune cells. With and without immune stimuli would be even better. I will write to Rob about this.
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DMissa
Senior Member (Voting Rights)
PS I want to add separately that monocytes and NKs are probably the biggest source of any sort of mitochondrial signal from mixed PBMC. If mitochondrial gene expression, rates of oxygen consumption or production of XYZ thing are often measured to be down in pwME this would instead suggest to me that NKs and/or monocytes are less functionally active or present (for both possibilities; proportional to the entire PBMC background. This is critical. There may be relatively more of the other stuff rather than less of these ones. Or maybe a combination.).