Vitamin D
By Jens Allmer
Vitamin D, technically a hormone, is made in the skin when UVB rays convert a cholesterol compound into D3 (Cholecalciferol, or Calciol). Many people don’t make enough due to lack of sun exposure, so we rely on food (like fatty fish) or supplements. Plants provide D2 (Ergocalciferol), but D3 works better in our bodies.
D3 has three key forms:
- Calciol: Stored in fat for long-term use; this is the form we produce or ingest.
- Calcifediol: Formed in the liver for short-term storage, circulating in blood and commonly tested to check D3 levels.
- Calcitriol: The active form, made in the kidneys, with a short lifespan but crucial for biological effects.
We’ll be using the terms Calciol → Calcifediol → Calcitriol throughout future discussions.
For more technical details, read on.
Vitamin D is actually a hormone that the body can produce in relatively large amounts, so it should not be called a vitamin. It is produced in the skin, where some form of cholesterol is converted to D3 by UVB.
That said, today, due to a lack of sun exposure, protective clothing, and sunscreen, most of us do not produce sufficient D3. Hence, we could rightfully name it a vitamin now. It can be ingested (fatty fish is an OK option that can give you 1000 IU / 100g), but some supplements provide far higher doses. Some plants contain vitamin D2, but D2 is inferior to D3 in the human body.
So far, we have heard of D2 and D3. Let’s look at their other names. D2 is also called Ergocalciferol, and D3 is called Calciol (another name is Cholecalciferol). There is just a small chemical difference between them. Remember Contergan? Minor chemical differences can have significant effects. Ergocalciferol seems relatively benign, though, and the pharmaceutical industry offers medications containing high doses (50000 IU) of It (D2). Examples of such drugs are Drisdol, Calciferol, Calcidiol, and Ergocal.
We need to explore D3 a bit more. Although everything I will discuss also applies to D2, only the names would differ, and the biological effect would be somewhat diminished. Otherwise, D2 and D3 look and act similarly.
Cholecalciferol is what we produce, eat, or supplement. That is one name for D3. Cholecalciferol can enter our fat cells and may be stored there until the fat is processed (historically on the order of months but today on the order of years). If so, it will be released alongside the energy. That worked great some thousands of years ago to provide enough D3 during the winter when the sun is weak in temperate areas.
Cholecalciferol can be stored in fat cells for later usage, but it is not the active form of the hormone. In the liver, Cholecalciferol is hydroxylated. That basically means the chemical structure is altered just a little bit. We then name the new molecule Calcifediol but also: 25-Hydroxyvitamin D3, 25-Hydroxycholecalciferol, 25-OH VitD3, and 25(OH)D3. This form of D3 is preferentially bound by a protein named D-binding protein (DBP) in the blood. In its DBP-bound form, Calcifediol can circulate in the blood for weeks. This is the form of D3 that we want to have checked when we look at our blood D3 levels.
Calcifediol is still not the active form of the hormone. Calcifediol must be hydroxylated again, this time in the kidney, to become active. Thereby, the active hormone D3 is produced. We name it Calcitriol but also: 1,25-Dihydroxycholecalciferol, 1,25-Dihydroxyvitamin D3, and 1,25(OH)2D3. This could also be tested in the blood to see whether you can produce the active version of the hormone. This would not be a good test to check whether your D3 levels are good since the turnover of Calcitriol is relatively fast (on the order of hours).
So we get the following recipe (Enough mention of Cholecalciferol; let’s use an alias I found that is shorter and makes more sense: Calciol.):
| Calciol + OH –> | Calcifediol + OH –> | Calcitriol |
|---|---|---|
| long term storage | short term storage | active form |
| produced in skin food, supplements |
Supplements exist | Medication (kidney failure) |
Vitamin D refers to all of these molecules which makes discussing the topic cumbersome since we don’t know whether we talk about D2 or D3, or any of the chemical modifications we just mentioned. Therefore, it would be good if we could use the names Calciol, Calcifediol, and Calcitriol to refer to the three forms of the hormone in the human body.
I realized that the amount of information on Vitamin D, I provide here and on all the linked posts, got a bit out of hand, but I am so intrigued that I just keep researching. An index might make the information more palatable.
Vitamin D Index
- Supplementing Vitamin D
- Vitamin D is a hormone (this page)
- Calciol
- Calcifediol
- Calcitriol
- Vitamin D production
- Ergocalciferol
- Solubility of D3
- Vitamin D Regulation
- Calcium
- Magnesium
- Vitamin K
Diseases associated with vitamin D
There is an abundance of diseases that have been associated with low Vitamin D levels. Some diseases are associated with high Vitamin D levels. Still, it seems the latter have additional underlying conditions, so high Vitamin D levels may not be causal but only constitute an association.
Diseases associated with high Calcitriol
Diseases associated with low Calcitriol
Osteoporosis Hashimoto’s
