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WHAT IS MAKING US SICK?
Above is an interesting table from the supplementary materials. It shows things patient plasma was uniformly low in (left side, under the heading "down") and things they were high in (right side, under "up).
It also shows whether being low or high was positively or negatively associated with four other factors: age, bmi, steps and self-reported functioning (sf36). What you're looking for is something that if you're low in it, makes you feel worse and take fewer steps each day, but isn't associated with age or bmi. Kynurenate is the best example: me/cfs patients are low in it, and the lower we were ,the less steps taken per 24h. it's not correlated with age or bmi so it is hopefully a pure indicator of severity.
DOGS, TRAPS, PROOF
When you go to
the wikipedia page for kynurenate you learn a couple of things. One is that it was first discovered in dog urine and is in fact named after dog (
Kyn in Greek) urine. But more importantly that it is made by breaking down tryptophan. Does that mean Robert Phair (
@HTester) onto something with his tryptophan metabolic trap work? I'm not sure.
There are two main subgroups defined in this work by Fluge and Mella. One has high tryptophan but low kynurenate. That certainly looks like there might be a failure to break down tryptophan, which is I believe the key idea in the metabolic trap hypothesis. (the other subgroup is low in both). It highlights the importance of defining the subgroup in which that trap might apply.
However (one of) Phair's theories is about the IDO enzyme that breaks tryptophan into the intermediate molecule
kynurenine. Whereas Fluge and Mella's data shows
kynurenine is normal, it is kynurenate which is low.
I know Fluge, Mella and Phair have been at conferences together and I have no doubt Phair has seen this data long before publication.
@HTester if you'd like to weigh in here on whether or not this data makes you want to slide down the catabolic chain to look at the breakdown of kynurenine into kynurenate, please do!
WHAT CAN I DO?
While Phair continues his modelling, you might be thinking about how to get better. Can you raise your kynurenate? one answer: Keto diets may raise levels of kynurenate in the brain (
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359463/).
If you're looking at ways to lift your levels of kynurenate that are plausibly safe and have anecdotal support in me/cfs - that may, maybe, possibly, be one. This has been studied because epilepsy is associated with low kynurenate and keto diets are good for epilepsy. (it makes me wonder if me/cfs is associated with
epilepsy, i must say i've not heard patients mention epilepsy in these pages much.)
Campesterol and also undecenoylcarnitine c111 (no link, science doesn't seem to know anything about this one) show the same pattern as kynurenate: low in patient plasma and the lower you go the less steps you take.
Thyroxine is the opposite: high and the higher you go the fewer steps you take. It is the thyroid hormone. Why is it high? I don't know but the full data shows we are low in the precursor amino acid, tyrosine, so it's not that we have too much of that. Another mystery!
)