The itaconate shunt hypothesis

[Verity]

My apologies if this has already been posted somewhere! I couldn’t find it. Dr. Phair is a very clear speaker, and I appreciated hearing an update on this hypothesis that I was at least sort of able to follow as someone without the relevant background.

 

[Hutan]

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.

 

[Mij]

My OAT 'energy production" panel:

Citrate levels- 263 (ref ref range: 400-2000)
Cis-Aconitase- 150 (ref range: 25-400) *within normal range
Isocitrate- 37 (ref range: 50-300)
2-Ketoglutarate 1 (ref range: 5-80)
Oxaloacetate 337 (ref range: 950-2800)

 

[Jaybee00]

X thread on trap hypothesis

 

[Trish]

X thread on trap hypothesis

Many of us can't see Twitter threads.
Can someone say whether this is just chat or has some valid scientific content?

 

[Jonathan Edwards]

Can someone say whether this is just chat or has some valid scientific content?

I thought even Robert had given up the metabolic trap idea.

 

[Mij]

Can someone say whether this is just chat or has some valid scientific content?

There are 24 tweets following his original. He goes on to explain the "tryptophan metabolism" theory and the "trap hypothesis".

 

[salin]

My apologies if this has already been posted somewhere! I couldn’t find it. Dr. Phair is a very clear speaker, and I appreciated hearing an update on this hypothesis that I was at least sort of able to follow as someone without the relevant background.

Have the studies cited here been discussed before – and have they been validated or rejected?

 

[Laurie P]

Many of us can't see Twitter threads.
Can someone say whether this is just chat or has some valid scientific content?

If you replace the x.com in the URL with nitter.net you'll be able to read the thread.

https://nitter.net/ZdenekVrozina/status/2036517833538994670?ref_src=twsrc^tfw|twcamp^tweetembed|twterm^2036517833538994670|twgr^|twcon^s1_&ref_url=

 

[Jonathan Edwards]

Have the studies cited here been discussed before – and have they been validated or rejected?

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.

 

[salin]

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]

Were there any ideas as to what scientists could test to prove or disprove the hypothesis?

Further tests ? I think you would have to ask Robert. I forget.

 

[wigglethemouse]

Just on the genetic possibilities, Rob did mention that there were gene mutations that might predispose someone to problems with the itaconate shunt. He mentioned for example that there are common mutations in CLYBL, an enzyme that acts on citramalyl-CoA, that reduce its effectiveness.

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.