Neither vitamin D3 cholecalciferol nor 25-hydroxyvitamin D (calcifediol, AKA, confusingly, "calcidiol") act as hormones. A hormone is a substance which by its level in the bloodstream (and perhaps the cerebrospinal fluid) affects the behaviour of cells, potentially anywhere in the body. This is endocrine signaling.
1,25-dihyrdoxyvitamin D calcitriol activates the vitamin D receptor much more than the other two compounds. It acts as a hormone when it is produced in the kidneys and goes into circulation, to control cells which are involved in several aspects of calcium-phosphate-bone metabolism. This is a genuine hormonal function, with a very low circulating level (usually below 1 ng/mL) - and it is the one hormonal function of the three vitamin D compounds.
Vitamin D3 (from UV-B skin exposure or supplements - there is very little in food or multivitamins) is hydroxylated over a period of days to a week in the liver and goes into long-term circulation as 25-hydroxyvitamin D. A good level of this is 50 ng/mL 125 nmol/L or more, because this is what the immune system needs to function properly.
Please see the Quraishi et al. 2014 https://jamanetwork.com/journals/jamasurgery/fullarticle/1782085 graph at the start of this page, where you will find link to and discussion of the vitamin D research articles which are most important to the proper functioning immune system: https://vitamindstopscovid.info/00-evi/ . The section there: 02-compounds - explains the three compounds properly, and shows why the immune system's use of 25-hydroxyvitamin D, to be converted (by individual cells, in particular cell-type specific circumstances) _intracellularly_ to 1,25-dihydroxyvitamin D, has nothing to do with hormonal signaling. This intracrine and paracrine signaling is within individual cells, or to nearby cells. Vitamin D (here using the term to refer collectively to the three compounds, though it is only 25-hydoxyvitamin D and 1,25-dihydroxyvitamin D which are involved) based intracrine (AKA, not quite correctly "autocrine") and paracrine signaling play a crucial role in the ability of immune cells to respond to their individual circumstances. The immune system is unaffected by the relatively stable, very low, hormonal level of circulating 1,25-dihydroxyvitamin D.
The most important thing to measure is 25-hydroxyvitamin D, since immune cells need 50 ng/mL or more to function properly, and while the kidneys can often get by with half this. The level of circulating, hormonal, 1,25-dihydroxyvitamin D is important for calcium-phosphate-bone metabolism, but this does not affect the immune system. If there are concerns about calcium-phosphate-bone metabolism, circulating 1,25-dihydroxyvitamin D should be measured, but as far as I know (I am an electronic technician and computer programmer, not a doctor) its level varies a lot between individuals and so on its own, the level does not tell us much about what might be wrong with calcium-phosphate-bone metabolism. Calcium and parathyroid hormone levels provide more more information.
Please read the research articles at: https://vitamindstopscovid.info/00-evi/ including on bodyweight ratios of vitamin D3 to supplement with per day, and the use of calcifediol to boost 25-hydroxyvitamin D levels safely over 50 ng/mL in clinical emergencies such as sepsis, COVID-19, Kawasaki disease and MIS-C. Also, though I have not cited it yet this page, please see Prof. Sunil Wimalawansa's recent article in Nutrients:
But it is not true that immune cells are not influenced by 1,25. It depends on the immune cell and activation state, but may be doubtful that 25 can fuel the majority of the needs even in cells where it is significant.
The models people are using are hypothetical and mostly based on cell studies. No one can claim definitive answers on this topic.
Neither vitamin D3 cholecalciferol nor 25-hydroxyvitamin D (calcifediol, AKA, confusingly, "calcidiol") act as hormones. A hormone is a substance which by its level in the bloodstream (and perhaps the cerebrospinal fluid) affects the behaviour of cells, potentially anywhere in the body. This is endocrine signaling.
1,25-dihyrdoxyvitamin D calcitriol activates the vitamin D receptor much more than the other two compounds. It acts as a hormone when it is produced in the kidneys and goes into circulation, to control cells which are involved in several aspects of calcium-phosphate-bone metabolism. This is a genuine hormonal function, with a very low circulating level (usually below 1 ng/mL) - and it is the one hormonal function of the three vitamin D compounds.
Vitamin D3 (from UV-B skin exposure or supplements - there is very little in food or multivitamins) is hydroxylated over a period of days to a week in the liver and goes into long-term circulation as 25-hydroxyvitamin D. A good level of this is 50 ng/mL 125 nmol/L or more, because this is what the immune system needs to function properly.
Please see the Quraishi et al. 2014 https://jamanetwork.com/journals/jamasurgery/fullarticle/1782085 graph at the start of this page, where you will find link to and discussion of the vitamin D research articles which are most important to the proper functioning immune system: https://vitamindstopscovid.info/00-evi/ . The section there: 02-compounds - explains the three compounds properly, and shows why the immune system's use of 25-hydroxyvitamin D, to be converted (by individual cells, in particular cell-type specific circumstances) _intracellularly_ to 1,25-dihydroxyvitamin D, has nothing to do with hormonal signaling. This intracrine and paracrine signaling is within individual cells, or to nearby cells. Vitamin D (here using the term to refer collectively to the three compounds, though it is only 25-hydoxyvitamin D and 1,25-dihydroxyvitamin D which are involved) based intracrine (AKA, not quite correctly "autocrine") and paracrine signaling play a crucial role in the ability of immune cells to respond to their individual circumstances. The immune system is unaffected by the relatively stable, very low, hormonal level of circulating 1,25-dihydroxyvitamin D.
The most important thing to measure is 25-hydroxyvitamin D, since immune cells need 50 ng/mL or more to function properly, and while the kidneys can often get by with half this. The level of circulating, hormonal, 1,25-dihydroxyvitamin D is important for calcium-phosphate-bone metabolism, but this does not affect the immune system. If there are concerns about calcium-phosphate-bone metabolism, circulating 1,25-dihydroxyvitamin D should be measured, but as far as I know (I am an electronic technician and computer programmer, not a doctor) its level varies a lot between individuals and so on its own, the level does not tell us much about what might be wrong with calcium-phosphate-bone metabolism. Calcium and parathyroid hormone levels provide more more information.
Please read the research articles at: https://vitamindstopscovid.info/00-evi/ including on bodyweight ratios of vitamin D3 to supplement with per day, and the use of calcifediol to boost 25-hydroxyvitamin D levels safely over 50 ng/mL in clinical emergencies such as sepsis, COVID-19, Kawasaki disease and MIS-C. Also, though I have not cited it yet this page, please see Prof. Sunil Wimalawansa's recent article in Nutrients:
"Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19" 2022-07-21 https://www.mdpi.com/2072-6643/14/14/2997 .
I didn’t say anything about hormones.
But it is not true that immune cells are not influenced by 1,25. It depends on the immune cell and activation state, but may be doubtful that 25 can fuel the majority of the needs even in cells where it is significant.
The models people are using are hypothetical and mostly based on cell studies. No one can claim definitive answers on this topic.
See chrismasterjohnphd.com/vitamind and scroll to the section on PTH and calcitriol for some references.