Calcifediol

By Jens Allmer

July 15, 2024

[Vitamin D](vitamin-d), also called calcifediol (the short-term storage form), is made in the liver from another form of vitamin D. It usually binds to a protein in the blood, which helps it stay in the body for weeks. If there's not enough of this protein, vitamin D can be broken down and removed from the body through the kidneys. When the body needs more of the active form of vitamin D (/vitamins/vitamin-d/calcitriol), especially for things like low calcium or immune system support, stored vitamin D is quickly converted. [Vitamin D](vitamin-d) levels in the blood can indicate if someone has a deficiency or not. If levels are too low (see table below), the body may struggle to make enough active vitamin D, leading to various diseases.

For more technical details, read on.

The name Calcifediol (aka vitamin D) refers to a hormone that is produced via hydroxylation of Cholecalciferol in the human liver. Calcifediol is typically bound to the D-binding protein (DBP) but can be unbound if there is not enough DBP. If unbound, it is typically degraded and excreted via the kidneys. When bound to DBP, Calcifediol is relatively stable and can circulate in the human blood for weeks. Unless it is converted to Calcitriol and used by downstream processes. If demand for Calcitriol is high, e.g., low calcium or challenges to the immune system, ‘stored’ Calcifediol is converted to Calcitriol quicker.

Chemical structure of Calcifediol

Chemical structure of Calcifediol. Calcifediol has a hydroxy group in position 25 where Cholecalciferol only has a hydrogen atom. This conversion typically happens in the human liver. Muscle cells can also perform this conversion, though.


Study	ng/ml	nmol/L	Interpretation
Guidelines	<12	<30	Severe deficiency
Guidelines	12-20	30-50	Deficiency
Guidelines	20-30	50-75	Insufficiency
Guidelines	30-50	75-125	Sufficiency
Guidelines	>50	>125	Excess?
Jones 2008	<100	<250	Likely safe.
Judson et al. 2001 Sommerville	100-140	250-350	optimal

Guidelines for Calcifediol levels in the blood and their clinical interpretation. Alternative explanations are given in the cited studies. The guidelines assume toxicity above 50 ng/ml. I personally side with the studies below and other studies that show higher blood levels without toxicity.

Calcifediol levels don’t refer to the active form of the hormone which is Calcitriol. However, with low levels of Calcifediol, the conversion to Calcitriol may be hampered, and the resulting levels of Calcitriol will also be low. Hence, Calcifediol is a good marker for the sufficiency of vitamin D in the human body.

In addition to Calcifediol, Calcitriol should also be measured in diseases where the conversion from calcifediol to Calcitriol is out of control. Examples are sarcoidosis, where too much Calcitriol is produced, and conditions like chronic kidney disease, where the conversion to calcitriol is often hampered, leading to lower levels of the active form of vitamin D.