Hi all, I couldn't find the specific area for the discussion around the D3 regimen thus the new thread.

I will start by saying that I have had wonderful results following Batch's regimen.

I am specifically interested to ask about the relationship between Vitamins A, D, E and K and how have the levels that are considered in the regimen been calculated / attained? I know Batch fondly, but I thought I'd post publicly for anyone else that was interested in the science / discussion.

I understand that Vitamin D is hydroxylated into an active steroid hormone, 1,25(OH)D, calcitriol, this active metabolite has been well studied for its effect to influence macrophage activation and the upregulation and expression of beta defensins and cathelicidens, two of many of the ways Vitamin D influences immune system function to protect against pathogenic bacteria and viruses etc. I note at this point it is interesting to see a U shaped curve in some of the literature (Chris Masterjohns review of Cochranes systemic Vitamin D / COVID studies) as 25(OH)D levels elevate above 70ng/ml with a negative correlation on outcomes at levels above 100ng/ml in respect to the current virus.

I also understand that in order for this to occur, the same process for how calcitriol downregulates neuroinflammatory peptides, calcitriol enters the cell, binds with the Vitamin D receptor, forms a heterodimer with the retinoid X receptor and then enters the nucleus to influence the Vitamin D response elements, in our case - the down regulation of CGRP, PACAP, VIP, SP etc.

What I did not understand until recently was that Vitamin A also behaves in much the same manner. Cells take up all-trans-retinol from retinol-binding protein or from retinyl esters transported by lipoproteins. Intracellularly, retinol is converted via isomerization into either 9-cis-retinol or 11-cis-retinol, followed by  oxidation into retinal and retinoic acid. It is the two metabolites of retinoic acid that activate the nuclear retinoid receptors, RARs and RXRs (sound familiar) - in this regard they too are able to enter the cells nucleus and influence the retinoic acid response elements referred RARE and control target gene transcription.

With that being said, if calcitriol via the nuclear Vitamin D receptor, as well as the isomers of Vitamin A, as well as AR, FXR, LXR, PPAR, PXR, RAR, TR - all have affinity for the RXR receptor, are they not then competing with each other in order to bind with RXR, form the heterodimer and influence genetic transcription, thus my question becomes how do we know what ratios of A, D, E, K (the fat soluble vitamins) were intended to be "floating" around fighting to access the RXR by natures standard and is that aligned in the regimen?

Whilst I have a confirmational bias that suggests Vitamin Ds active metabolite winning the fight for affinity with the RXR receptor is a very good thing for me - it stopped my cluster headaches, at what cost may I be preventing the other hormones from influencing their signalling pathways?

Food for thought, I just wondered if any brain box out there was able to explain to me how a selection is made as to what binds with the RXR in order to influence genetic transcription, i.e. by serum concentration? by lucky dip? by preferential selection based on other signalling pathways? Your answer will help me sleep tonight.

Thanks guys, love yourself, love your friends, love your family.

VR, Craig.