Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients 2023, Glass, Hanson et al

[forestglip]

Some of the above about how normalization might affect this gets a bit out of my comfort zone, but overall, I think we're basically coming back around to the idea that there may be more variability in deltas in specific metabolites. Exemplified by this amazing illustration:



Scenario #1 with ME/CFS, where there is a much smaller mean change, and a similar spread, is what would make you more confident about a "lack of change". In scenario #2, where even though the overall mean change is zero, there is a wildly larger spread in changes. Making you think it's not simply a "lack" of change, but more like some patients are changing just as much as HC, while others are changing just as much in the opposite direction.

And there still might be an interesting difference between groups (or maybe not super interesting), but where the difference is more like the ME/CFS group's metabolites are dysregulated and go all over the place while the HC group's metabolites consistently increase, as opposed to a "lack of adaptation".

Getting closer?

 

[jnmaciuch]

Some of the above about how normalization might affect this gets a bit out of my comfort zone, but overall, I think we're basically coming back around to the idea that there may be more variability in deltas in specific metabolites. Exemplified by this amazing illustration:

View attachment 30403

Scenario #1 with ME/CFS, where there is a much smaller mean change, and a similar spread, is what would make you more confident about a "lack of change". In scenario #2, where even though the overall mean change is zero, there is a wildly larger spread in changes. Making you think it's not simply a "lack" of change, but more like some patients are changing just as much as HC, while others are changing just as much in the opposite direction.

And there still might be an interesting difference between groups (or maybe not super interesting), but where the difference is more like the ME/CFS group's metabolites are dysregulated and go all over the place while the HC group's metabolites consistently increase, as opposed to a "lack of adaptation".

Getting closer?

Yep pretty much. The reason I keep harping on the distinction is because its the only way I can see to reconcile these results with the plasma findings—i.e. there are changes after exercise, but what comes out in the urine has more layers of complication for the analysis, making it look like there’s “no change.”

Otherwise we’re just kind of left with completely opposite conclusions from two papers and less reason to trust either set of findings

 

[forestglip]

Gotcha.

i.e. there are changes after exercise, but what comes out in the urine is has more layers of complication for the analysis, making it look like there’s “no change.”

Can it just be metabolites related to two different systems? As in the metabolites in plasma that change due to exercise being involved in pathways that are unrelated to the pathways that make urine metabolites increase.

 

[jnmaciuch]

As in the metabolites in plasma that change due to exercise being involved in pathways that are unrelated to the pathways that make urine metabolites increase.

You expect that specific metabolites would be significant in one analysis and not the other. But the kidneys exist to keep blood concentrations within specific ranges by filtering out excess, so one kinda has to be an echo of the other unless kidney function is just breaking down (in which case you’d have other issues)