PRIME International Symposium, September 28-29 2026

[Dude]

There’s actually a pretty interesting connection to Wirth’s HIF-1α model. He proposes that hypoxia/ROS could activate HIF-1α, leading to increased extracellular matrix/collagen production and thickening of the capillary basement membrane. That could then further impair microcirculation, creating a kind of vicious cycle.

Of course, this is Wirth’s hypothesis and hasn’t been demonstrated by the Wüst study itself.

 

[Jonathan Edwards]

He proposes that hypoxia/ROS could activate HIF-1α, leading to increased extracellular matrix/collagen production and thickening of the capillary basement membrane.

Except that 150 years of histopathology of basement membranes has not shown this happening in any other hypoxic situation, as far as I am aware.

In other branches of medicine one doesn't get this sort of smog of evidence-free theorising.

 

[obeat]

The other problem with the basement membrane theory is that if you improve you have to then explain how the membrane "unthickens".

I also cannot see how these microclot /microcirculation theories can explain intraday fluctuations.

How does it explain alcohol intolerance present in about 75% of sufferers?

ETA if it's constitutional why have no connective tissues genes shown up in GWAS studies?

 

[Andy]

I also cannot see how these microclot /microcirculation theories can explain intraday fluctuations.

Or how they cause ME/CFS when it is claimed they appear in other conditions as well.

 

[Jonathan Edwards]

Or how they cause ME/CFS when it is claimed they appear in other conditions as well.

And of course, being in the systemic circulation, they would have effects on all tissues, not just muscle.

 

[hotblack]

Or how they cause ME/CFS when it is claimed they appear in other conditions as well.

Does it need to be causal though? I can see how they could exist as a downstream effect of other things and so still interesting/useful.

 

[Andy]

Does it need to be causal though? I can see how they could exist as a downstream effect of other things and so still interesting/useful.

I agree, if they exist at all. However, as I understand it, the microclots enthusiasts believe they are causal for whatever condition they happen to be studying.

 

[Jonathan Edwards]

Does it need to be causal though? I can see how they could exist as a downstream effect of other things and so still interesting/useful.

Everyone talking about them assumes they are causal.
And if nobody has yet worked out why these lumps are there in the thioflavine T preparations I am not sure how useful they are going to be.

 

[hotblack]

I agree, if they exist at all. However, as I understand it, the microclots enthusiasts believe they are causal for whatever condition they happen to be studying.

Ah. Yeah, that doesn’t seem a convincing conclusion.

I don’t know what it would mean if they exist. It’s not an area I’ve paid much attention to and have little understanding of. I’ve been doing s bit more reading recently but it’s pretty basic stuff.

But some sort of subtle changes caused by other changes is I think what @jnmaciuch is talking about?