This is my first pass review, though I would love to see further discussion and checking by someone with a stronger stats background than I have, particularly with regard to checking for false positives:
Metabolic features of chronic fatigue syndrome
Naviaux et. al. , published in PNAS Plus.
22 males and 23 females met Fukuda, CCC and IOM criteria. There were 18 and 21 controls respectively.
The data clustering appears to be non-overlapping between controls and patients. (Figure 1), though this might not be an accurately reflection given that ranges are not shown.
A heading in the results section summarizes the paper in one line: Homogeneous Metabolic Response to Heterogeneous Triggers. You can find detailed discussion of those findings in the appendix here:
http://www.pnas.org/content/suppl/2016/08/24/1607571113.DCSupplemental/pnas.1607571113.sapp.pdf
This is exciting for me because many of the speculations about biochemistry that I was debating with people in the late 90s and early 2000s touched on these things from time to time. They identified over 60 candidate metabolites, and later looked at which were most diagnostic.
The next heading is particularly important: Metabolites Correlated with the Clinical Severity of CFS. They have attempted to control for false discovery, though I have not looked at that level of detail in the appendix just yet. They conclude:
I am not going to discuss all findings, just the ones I currently find interesting. Its a really long list, and I don't want to just quote huge lists of issues and hypothesized issues.
The decreased sphingolipid and glycosphingolipid findings are different from found in the metabolic syndrome and the acute cell danger response, and it looks like CFS is the opposite of an acute cell danger response. I found this bit very interesting, and might indicate that the ME or CFS response is a conserved evolutionary response:
Later on they said as much, here:
This is one of the things I recall being discussed in the 90s. Indeed, I have commented many many times that CFS might be triggered in an attempt to combat potentially life threatening infections, especially in heart and brain.
Cholesterol synthesis is lowered? This is surprising to me.
Uric acid was low in males, and adenosine in females. I wonder what this implies for me as my uric acid is always high.
Two of the amino acid findings are not what you would expect from acute inflammation or infection. However other findings in the paper suggest otherwise. Its not a clear issue.
FAD, or flavin adenine dinucleotide, appears to be low, and so you might expect B vitamin issues and especially problems with lipoic acid and glutathione.
Increased arginine, which I think is suspected in susceptibility to herpes virus infections, seems to be associated with decreased post operative infection as well. Hmmmmm ...
HICA, or 2-Hydoxyisocaproic acid, was low, which might mean suseptibility to bacterial and fungal infection.
There is an interesting quote that reflects possible treatments: Our clinical experience suggests that symptom improvements can be achieved more reliably by addressing the personalized abnormalities rather than by assuming a chemical abnormality without actual measurement.
They write about similarities to the dauer state, a type of hibernation, but in a fast look at some literature it appears to be more about dormant nematodes (worms) and not bears. They survive hostile conditions this way. They say this:
This I found very interesting given my personal health:
One long term therapeutic research direction is to investigate the role of NADPH.
The importance of this study is summed up near the end:
If validated I think these findings will change ME research forever. I really hope they can be shown to be accurate, and that further studies will expand on these findings, lead to better patient cohort selection, and selected biochemical targets for intervention. Exciting times ...
