Comment by emsign
4 days ago
It is definitely a thing. It all fits with the mitochondria theory: after physical or mental exhaustion (increased metabolic turnover provided by mitochondria) the recovery time (sleep) for ME/CFS patients is increased to such a degree that normal daily tasks gets them into a energy low they can't recover from anymore.
Except there isn't any evidence of mitochondria problems in ME/CFS, even though a lot of studies have looked at them.
I don't think that's quite right? There's been a fair amount of evidence pointing at possible issues, but there's no clear answer due to poor (or just different) study design, small sample sizes, different criteria across studies, different sample groups, etc.
So eg https://translational-medicine.biomedcentral.com/articles/10... reviewed 19 studies, many of which did find "evidence of mitochondria problems", but concluded:
> ...it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID. [...] There is consistent genomic research suggesting that ME/CFS/SEID is not a primary mitochondrial disorder, however, mitochondrial decline might occur due to secondary effects of other disrupted pathways. [...] As population samples were small, these results should be interpreted cautiously.
I wouldn't summarise that as "no evidence". It's more like "ME/CFS doesn't seem to be a genetic disorder causing defective mitochondria, and the mitochondria look the same, but they seem to function differently for some reason even if we lack enough data to figure out why yet". Note that, eg, of the 19 studies reviews, 5 tried to check for differences in mitochondrial respiration between ME/CFS patients and healthy controls, and 4 of the 5 found notable differences; one study was able to reliably detect if a cell sample came from a ME/CFS patient or a healthy control based on measuring mitochondrial respiration.
I don't know that's enough to fully reject the null hypothesis just yet, but it's certainly not clear we can accept it either.
No well replicated studies.
>they seem to function differently
Except there isn't evidence showing this.
>5 tried to check for differences in mitochondrial respiration between ME/CFS patients and healthy controls, and 4 of the 5 found notable differences
But did they look at the same thing? I also don't think that includes all the studies that failed to show mitochondrial differences, and failures to replicate previous studies.
There is the recent Ryback study (currently a preprint) which failed to replicate Fluge and Mella's result, and showed no difference from controls. There is the Tomas study which showed no difference in the ATP profile test from controls. Also, a 2019 Tomas study showed no difference in respiration between patients and controls.