Digging deeper into the B6 metabolism and riboflavin connection..
B6 metabolism relies heavily on riboflavin metabolites, as FMN (and cofactors magnesium, zinc):
Therefore, if riboflavin (as FAD, FMN) is being depleted you could expect LARGE bottlenecks in B6 metabolism and accumulation of B6 metabolites.. which leads to neuropathy.. and more.
Some recent metabolomics work that looks ..hauntingly familiar.. to the disease model I've been describing also noted a-KGDH and
succinate dehydrogenase (SDH) impairments -
https://www.medrxiv.org/content/10.1101/2021.06.14.21258895v1 So let's take another look at the TCA cycle again and examine what may happen if ROS is high and therefore a-KGDH is proportionally low.. and if riboflavin is now decreased:
Riboflavin metabolism consumes magnesium and riboflavin->FAD depletion can
further impair a-KGDH, putting more pressure on P5P via [B12, folate + P5P] (and BCAAs)
and [GABA + P5P] (GABA shunt) to fill in the shortfall at succinate, creating a riboflavin-based
"metabolic trap" at a-KGDH, by continuing the cycle of depletion involving P5P.
https://www.sciencedirect.com/science/article/pii/S0005272816300597Riboflavin is particularly
difficult to absorb from diet/supplements -
Riboflavin depletion may create a further bottleneck at SDH, which may increase ROS.. which further reduces a-KGDH:
Which then puts more pressure on the urea cycle to perform and "fill in the gap" at fumarate.. which is fine for a while, as we have plenty of nitrogen to get rid of:
However, this then puts more pressure on aspartate and argininosuccinate until that fails also. We now have hypoxia, potential lactate issues + connective tissue disorders downstream of HIF-1a signalling and prolyl hydroxylases.
So in this way, chronically high ROS can becoming a trap that causes B6 toxicity and all of the downstream cascade of issues we see in CFS/ME, if P5P is able to be maintained.
If the initial ROS is being created by viral mTOR activity, the best solution is to
turn that off.For HHV-related activity, the triterpenes and beta-glucans in reishi have provided some rather good early results, as has spironolactone, however these don't do anything useful for
other infections that subvert a different energy pathway, eg. fatty acid oxidation (FAO).
If anything, the metabolic patches which normalise HHV behaviour can
exacerbate the problems created by these other pathogens.
This is where I'm heavily focused at the moment.For now, as a
temporary patch - aspects of v1 and v2 protocol may be appropriate for managing these other infections.
https://www.hindawi.com/journals/sci/2020/2016809/Regular small doses of succinate (as also found in
high-dose apple cider vinegar capsules) and high dose R-ALA (both 3-4 x day), plus an initial increased frequent intake of riboflavin to help unblock the "metabolic trap" and keep things balanced, may be quite useful in preventing B vitamins was being turned into nitrogen and urine, unblocking other metabolic pathways.
By supplementing succinate directly (and not overdosing on it), this prevents the drain on all of the metabolites.
(This may be around 75-100mg of succinate, 3-4x a day.)
A reportedly successful "lite" of v2 simply consisted of 2-3 high dose ACV capsules + 400mg R-ALA, 3-4x day, some eggs and otherwise maintaining a clean diet.
"Brute-forcing" a-KGDH with "very high" doses of thiamine (reports of 1g/day), or more usually as derivatives such as benfotiamine, sulbutiamine has also been reported by people as very helpful.
