After 23 years of this malady and having tried many different things. I am more leaning towards a neurotransmitter problem and/or a inflammation issue. I am also leaning towards a methylation problem.
I keep on telling people on the forum that the POIS symptoms are identical to a crash episode of a Chronic Fatigue Syndrome.
Which can also taper in at least 48 hours, but can last longer. The parallels are uncanny. The difference is that although some people have both POIS and CFS, most people with CFS do not have POIS.
However I believe the underlying mechanisms are the same.
CFS is now know to be a severe inflammatory disorder with inflammation of the brain. Inflammation markers are chronically elevated.
The brain inflammation can not be detected by current regular patient tests, but has been clearly identified in research papers using advanced technologies not commonly used outside research. The inflammatory markers in question are not tested in the usual testss doctors ran. Mine were test at NOVA's center for neuroimmune medicine and they were categorically off and clearly show that there is sever chronic inflammation in many key markers;.
All the brain issues are for POIS and CFS. POIS being in my case more severe but shorter. The flu like symptoms as well. Fatigue etc.
I have both POIS and CFS. I already posted what works for me. Helps eliminate some does not eliminate issue:
Keep in mind that am writing this on day zero of an O, also on day 2 of another 0, and on day 4 of 2 Os. Without the support below I would be in big trouble.
immunocal whey protein. NOT regular whey protein. NOT any other brand (immuplus worked but no longer produced).
Take half a pack to start with in empty stomach before breakfast. Increase to a pack a week. Second half pack at about 2:30 PM on empty stomach.
After a week on a full pack per day you can experiment on increasing to two packs per day. It is important not to eat for at leas 15 minutes after taking it. And it is very important no to start at full dose!
Improvement is noticeable at about one pack a day. It works within 20 minutes for me. It makes me want to sleep for 15 minutes after taking it. I obey. Afterwards my neurotransmitters are far improved and I can deal with life a lot better.
I just had 3 Os in 4 days, (married 26 years), I take a full pack afterwards now in addition to regular pack. Eat chicken and red quinoa for protein with two eggs with sunny side up (liquid yokes). It removes a lot of the misery. Specially the mental misery.