Vit D and calcifediol

With Dr. David Grimes.
During the Covid-19 pandemic of 2020 there was a great deal of pressure on the intensive care units of our hospitals to admit patients who were seriously ill, and there appeared to be no way of preventing this.
However, there was good news from Córdoba in Spain.
Before the pandemic I was aware of the importance of optimising defensive immunity so as to minimise the effect of infection on our bodies. The way to achieve this was to correct vitamin D deficiency, knowing of the vital importance of vitamin D in initiating and maintaining the necessary escalation of the defensive immune process at the time of infection. It was also known that vitamin D deficiency is very common.
When I was attempting to advocate the use of vitamin D in the community and in the hospitals at the time of the emergence of the Covid-19 pandemic, my attention was drawn to a research paper published in the New England Journal of Medicine in
December 2019. This paper described the use of vitamin D when given to patients in an intensive care unit, and it conferred no advantage compared to patients who had not received vitamin D.
The study was a randomised controlled trial (RCT) involving 1360 patients who were vitamin D deficient and who required intensive care support. 1078 were severely deficient with blood levels of vitamin D less than 20ng/ml (50nmol/L). The half randomised to receive vitamin D were given a single dose of 540,000 units by mouth or by feeding tube.
https://www.nejm.org/doi/full/10.1056...
The result was very discouraging as it was clear in my mind that vitamin D should have been of considerable benefit. Information from Brazil became available later during the pandemic and the conclusion was the same, that vitamin D conferred no benefit when given to Covid-19 patients on admission to intensive care units.
But there was information available at the time explaining that it was inevitable that vitamin D given to critically ill patients was unlikely to be of benefit.
All became clear when we received the results of two randomised controlled clinical trials from Spain, from Córdoba and then from Barcelona.
Hydroxylation of Vitamin D to Calcifediol
What was known (by a few) before the pandemic is that the process of partial activation of vitamin D in the liver is very slow. When vitamin D is produced in the skin as the pre-hormone cholecalciferol, or when it is taken by mouth or by injection, it is taken in the blood to the liver. It is then hydroxylated, that is a hydroxyl group (-OH) is added to the molecule, which then becomes 25(OH)D, which is also known as calcifediol (or calcidiol). It then circulates in the the blood as this reservoir form. When necessary, it is taken up by appropriate cells (such as the cells of the immune system, especially T-lymphocytes) to be converted immediately into the active form 1,25(OH)D, also known as calcitriol.
Within the cells 1,25(OH)D attaches to and completes the Vitamin D Receptor (VDR) molecule, thus enabling activation of the genes that escalate the defensive immune process. At this stage the escalation process is very rapid. The cells can synthesise any number of VDR molecules, but the 1,25(OH)D molecules can be used only once and then they are inactivated by conversion into 24,25(OH)D. This means that there must be a constant supply of 25(OH)D, calcifediol, available from its reservoir in the blood.
Unfortunately most people have sub-optimal blood levels of vitamin D as 25(OH)D, and so the supply might not be adequate to maintain the immune process at a time of crisis. A further supply would be essential during a serious illness, for example sepsis or Covid-19, in which the risk of death is high if admission to hospital has been necessary.