Some thoughts on the article, now I've had time to read it in its entirety:
The authors have read the right people and understand the nature of the illness - Maes, Carruthers, etc. I like that they say that the etiological mechanism has "predisposing, triggering, and maintaining factors".
The study involves 3
4 females with ME/CFS (34.9+/- 1.6 SE y.o.) and 25 non-ME/CFS females (33.0 +/- SE y.o.). Other participants were ruled out, including male patients with ME/CFS (sorry guys!) and people who were outliers age-wise. The dx criteria used was the
Canadian Consensus; the non-ME/CFS patients were examined and it was determined they were not suffering from any major illness.
A limitation of the study is that they appear to have all come from the
same clinician. This may mean the same area, which may mean the same/similar initial insults.
Absolute concentration of six blood metabolites were significantly altered in ME/CFS patients:
- Blood glucose was increased.
- The following were decreased: acetate, glutamate, hypoxanthine, lactate, and phenylalanine
Relative concentration of six metabolites were significantly altered in ME/CFS patients as well:
- Blood glucose and aspartate were increased.
- The following were decreased: acetate, glutamate, hypoxanthine, lactate, and phenylalanine
- ....and were positively correlated to one another for both ME/CFS patients and controls
- ....and were positively correlated to alanine, glycine, ornithine, serine, and total metabolites for both ME/CFS and controls
I find this part especially interesting. I'm not surprised glucose is increased rather than decreased; I think based off of a few experiences that my blood sugar is off. I'd really have to look at the others, though. I've heard of xanthine, but not hypoxanthine (puts on research hat).
In urine rather than blood, all absolute concentration metabolites were found to be decreased in ME/CFS: acetate, alanine, formate, pyruvate and serine. Those plus valine were decreased in the relative concentrations - although there was increased allantoin and creatinine.
I find the latter fascinating. I know allantoin in the context of plants; it's a wound-healer present in comfrey plants, though in this context it's a purine product of uric acid? And I think we have all had our fill regarding what creatinine does.
It also seems that in the non-ME/CFS group, glucose was inversely proportional to hypoxanthine, lactate, and phenylalanine. In the ME/CFS group, acetate showed positive correlation to glutamate, hypoxanthine, lactate, and phenylalanine.
Conclusion?
The altered amino acid concentrations appear to be connected to those important to the citric acid cycle; and other metabolites appear to point to disordered glycolysis.
So... we have trouble processing carbs? Huh. Also not terribly shocking.
If the amino acids that are involved in the citric acid cycle are drastically decreased and glucose is high, this may point to impaired glycolysis... and an over-utilization of the citric acid cycle to compensate, resulting in depleted amino acids.
The article then makes a particular point of how, only in the ME/CFS cohort did glycolysis products go down while amino acid waste went up, implying lower rate of glycolysis and a higher rate of the Krebs (Citric Acid) cycle, instead. In the healthy patients, these values did not directly correlate positively OR negatively.
The authors go on to then postulate that ME/CFS patients have a depletion of non-essential amino acids because they're being used to push the Krebs Cycle...
@Gondwanaland, then they DO go into the oxalate cycle...
They point out that blood glutamate is positively correlated with arginine and negatively correlated with glucose in the ME/CFS group, again implying a compensatory mechanism for impaired glycolysis, this time through the transformation of oxaloacetate to aspartate using aspartate trasaminase, when glutamate is deaminated to 2-oxoglutarate.
Huh. So we have trouble using glucose, so we use glutamate, instead. And the more trouble we have using glucose, the
more we need to rely on glutamate; that is why these, too, are inversely proportional in ME/CFS patients.
THEN THE RESEARCHERS INCLUDED the energy cycle diagrams for glycolysis, and the Citric Acid Cycle, and urea cycle - because they are just that awesome.
(will be continued in a bit, guys).... (and sorry all the pretty (
copyrighted) images disappeared!)
-J