Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases, 2019, McGregor et al

Open access at https://www.mdpi.com/2075-4418/9/3/70

 

What does this tell us about the illness?

 

This looks like a really interesting lead. I hope more research follows!

 

@Jonathan Edwards, @MEMarge

 

Yes, although I would suggest GET has not been proven safe for any ME severity level. There seems to be a lot of anecdotal evidence that those severely affected might not have become severe, if they had avoided GET whilst still mild or moderate.

 

Sounds really interesting

 

So that would make it independent validation of this? I don't see Shukla on this paper.



From the wikiwikiwik:

Abnormal, but how much so?

 

There now exists plenty of evidence that something is going wrong with exertion in ME even if it has not been pinned down.

 

I do get the impression there may be a correlation between food intolerances and ME. So many pwME seem to have a variety of food intolerances, including my wife; seems the prevalence could be higher in pwME than the general population? Could certain foods provoke certain bacterial gut leakages in certain people? And more so in pwME? Or could some pwME experience something that masquerades as food intolerance, but is actually different? Or is food intolerance a generic term, that can include gut leakage issues anyway?

And note I am not confusing intolerance with allergy, which I'm fully aware are very different.

 

It seems to have been started in 2010!

 

I find this interesting. Study sample collection started 2010 - a long time ago.

and the results were previously published

And this paper looked at the results of the previous study to try and derive a hypothesis

That in addition to saying replication is needed, they suggest avenues to follow up on in future studies

So how did this hypothesis come about now, many years later. (from Video Link : https://mecfsconference.org.au/videos/neil-mcgregor/ )

The power of collaboration, sharing, discussion, challenging!

 

cc : @wigglethemouse @ScottTriGuy @Perrier


Another close call by Network Analysis in 2017. Observe the node named "Xanthine Oxidase", next to Urea Cycle :

Below, snapshot from one page from a document i sent to several ME/CFS researchers, March 2018 :

 

From Wikipedia:

Inosine pranobex = Imunovir. This and the supplement inosine have have both been used anecdotally by patients and clinicians. (This isn't a recommendation, by the way.)

If this adds up, it could be interesting and might suggest treatments.

Of course, it's a tiny sample, so we shouldn't get our hopes up. But it is interesting.

 

I think they are suggesting that the energy metabolism problems might be a downstream effect of a problem affecting the purine metabolism.

 

Tweet from Dr. John Whiting who I believe is closely connected with the researchers of this paper
https://twitter.com/user/status/1146762215254401024

https://twitter.com/user/status/1146783659380240384

https://twitter.com/user/status/1146783384414216192

https://twitter.com/user/status/1146791311103668224

 

@mariovitali Can you take a look at the supplementary data to see if any of those genes pop out to you.

Supplementary data. Post Exertional Malaise, Hypoacetylation and Purine metabolism
deregulation in ME/CFS Cases
https://www.mdpi.com/2075-4418/9/3/70/s1

 

As far as I can tell, the science on food intolerances is about as chaotic as that on "chronic fatigue", the symptom™. So really impossible to say until that moves forward from the starting line of "there may or may not be such a thing as food intolerance, or something like it".

It's quite likely that the thinking about food, rather than specific compounds and their interaction with gut microbes, may be the issue here. Food is made up a crapton of smaller stuff and the science is just far too immature to help guide us.

Kinda similar to the exosome and microbiome hypotheses, the science of ME is opening all sorts of possible avenues but they're all freaking unexplored and need to do some maturing all on their own before they are of use to us.

 

There are some things I don't quite understand in this paper. For example, it reads that "hypoxanthine was the prime predictive variable for alterations in the PEM scores". But if you look at the data, the ME/CFS group with no PEM after 7 days had larger differences for hypoxanthine compared to controls, than the ME/CFS group with PEM.

Also not sure what this means (my bolding):

So these markers did not correlate with PEM in the ME/CSF group? What do they mean with the whole group analysis- the analysis that includes healthy controls?

Even if these abnormalities compared to healthy controls (it isn't that difficult to find differences between ME/CFS patients and healthy controls) are robust, I don't see how they would have to be associated with PEM. If I wanted to figure out the biological correlates of PEM, I would test patients and controls in rest and then after exertion. If a marker is normal in all states except for ME/CFS patients after exertion, that would suggest that it might have something to do with PEM. As far as I can see, the abnormalities found here could be unrelated to exertion. Or did I miss something?