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Gets samples from the clinic (Haukeland University Hospitals) from RituxME and CycloME clinical trials
Did metabolomics on the samples
Did metabolomics on the samples
Energy metabolism
main energy pathway under aerobic conditions
glucose ->pyruvate->Acetyl-CoA goes into Kreb cycle
(dependent on presence of oxygen)
main energy pathway under aerobic conditions
glucose ->pyruvate->Acetyl-CoA goes into Kreb cycle
(dependent on presence of oxygen)
Under anaerobic conditions, hypoxia
glucose->pyruvate->lactate (high lactate is clue having hypoxic conditions)
"We think this (high lactate) is very relevant."
#TheAcidTest
glucose->pyruvate->lactate (high lactate is clue having hypoxic conditions)
"We think this (high lactate) is very relevant."
#TheAcidTest
#MECFS similarity to anaerobic metabolism
PDH inhibition leads to more lactate, less energy, altered use of fuels
PDH inhibition leads to more lactate, less energy, altered use of fuels
measure molecules in the blood like glucose, lactate, amino acids, lipids, ketones, vitamins, etc.
Same papers looking at changes in lipid metabolism:
Naviaux, 2016
Germain, 2017
Nagy-Szakal, 2018
Che, 2022
Same papers looking at changes in lipid metabolism:
Naviaux, 2016
Germain, 2017
Nagy-Szakal, 2018
Che, 2022
changed levels of energy fuels in the blood can show signs of stressed energy metabolism
Some hypotheses:
organelle dysfunction, oxygen and fuel supply, PDH inhibition, kynurenine pathway
Unifying metabolic phenotype for #MECFS hasn't been found and so far no biomarkers
Some hypotheses:
organelle dysfunction, oxygen and fuel supply, PDH inhibition, kynurenine pathway
Unifying metabolic phenotype for #MECFS hasn't been found and so far no biomarkers
Papers finding reduced amino acids:
Niblett, 2007
Armstrong, 2012, 2015
[missed others]
Niblett, 2007
Armstrong, 2012, 2015
[missed others]
Lien 2019 - abnormal lactate levels during exercise in #MECFS
Believe that this is not due to deconditioning
Baseline levels patients have a little higher than controls
Believe that this is not due to deconditioning
Baseline levels patients have a little higher than controls
Studying fuel switching mechanisms
Something in #MECFS blood stresses cellular energy metabolism (Fluge et al., 2016)
Led to increase in lactate and oxygen consumption
Something in #MECFS blood stresses cellular energy metabolism (Fluge et al., 2016)
Led to increase in lactate and oxygen consumption
Saw increase in PDK5 (inhibits PDH), cells shift to fatty acid degradation as an energy pathway
Data support a metabolic switch to an energy restricted state
ME patients look like intermediate state of starvation
Data support a metabolic switch to an energy restricted state
ME patients look like intermediate state of starvation
Hoel et al., 2021 - map of metabolic phenotypes in patients with #MECFS
measured 610 metabolites - 159 significant differences found
Found 3 subtypes (one of them is closer to healthy controls), can see difference in function score between types
measured 610 metabolites - 159 significant differences found
Found 3 subtypes (one of them is closer to healthy controls), can see difference in function score between types
Looked at confounders, sex, BMI, meds, diet, age, fasting effects
Conclusion: subgrouping wasn't due to these
Conclusion: subgrouping wasn't due to these
There's a struggle for energy, decreased oxygen extraction, lactate overproduction, physical debilitation
Activity can lead to worse Sx (PEM) - what factors?
Maybe autoimmune mechanism -> vascular dysregulation -> adaptations
Activity can lead to worse Sx (PEM) - what factors?
Maybe autoimmune mechanism -> vascular dysregulation -> adaptations
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