Thanks for this. I've just read the stressed mice study about first decreased, then significantly increased BA levels in the ileum, alongside drastically decreased free amino acids and a microbiotic shift.
So actually increased (ileal) BA levels associated with bad outcomes... ileal bacterial dysbiosis and overgrowth... Free-amino-acid starvation of beneficial ileal bacterial species... Due to lack of digestive functions in the more proximal parts of the GI system? Which more BA in the proximal parts would prevent and heal? Hence indeed the preference for uncoated BA instead of slow-release formulas as you suggest. I'll heed that founded advice.
At first, that study turned me somewhat angry for contradicting the model about lack of BA. But I take it's a cascade of which it is best to start at the top.
That study actually touches on and summarizes so many crucial elements of health. Not least when thinking about sprue or disaccharide intolerances or the vaguely ominous biogenic amines burden. Look at those dwindling goblet cells and exploding serum LPS and villous atrophy:
alt text
In the black-and-white bar graph above: Obliterated H3-acetylation by chemical injury (DSS).
Where did you derive or read the <200mg Na-But dose from? In that mice study they used 20mg∙kg−1.
Reduced BA uptake in the chronically inflamed states. So it'd be better to really blast up the dosage? Perhaps even so much as to provide BA through serum circulation and the basal membrane (from within the body) instead of the apical side (from the intestinal lumen)?
From Protective CO2 and aging:
Prolonged lack of CO2, i.e. also hypoxic states -> epigenetic silencing/hibernation. Got it! That seems sensible to apply!
I'm not fan of methionine. E.g. a high methionine, low cysteine ratio in many vegan protein powders feels very unsatisfactory for me. Betaine or trimethylglycine don't feel well either. Accordingly, red beets are a horror. IME, after a 2-3 days' subjective boost, those methyl donors can really worsen things. Yet merely avoiding their overabundance is insufficient in itself to put things back on a right track. The same with the idea of nicotinamide to deplete methyl-groups: That never worked for me. Choline however is really important for liver functions, chylomicrons etc. That thinking about the absolute dietary supply of methyl groups must either be way too simplistic or a mere drop in the ocean of stronger factors.
Speaking methylation: That's an ambiguous mechanism because whilst we don't want excessive methylation of DNA CpG sites which prevent genetic transcription, methylation of the lysine groups on histone bodies either contributes to their unfolding OR to genetic silencing.
On H3K9 tri-methylation (reportedly a stubbornly long-term, transgenerational impact!) acts silencing so directly opposes the effects of acetylation or bOHB. Which makes HDACis like butyrate or beta-hydroxybutyrate direct antagonists to overmethylation. I wish Peat had followed that up.
It could be rewarding to find out about the histone demethylation mechanisms for H3K9 specifically.