What is free 25OH Vitamin D?
Due to its hydrophobic nature 25OH Vitamin D, and other Vitamin D metabolites, circulate on binding proteins. About 90% of the total circulating 25OH Vitamin D is bound to the so-called Vitamin D Binding Protein (VDBP or DBP). The remaining 10% are bound to albumin, the main protein of human blood plasma. Although the affinity of albumin towards 25OH Vitamin D is much lower than the affinity of VDBP, the high concentration of albumin compensates for this difference.
A tiny fraction representing 0.04% of the total 25OH Vitamin D concentration circulates as the free form, or free 25OH Vitamin D.
Why is free 25OH Vitamin D important?
The conversion of 25OH Vitamin D into the biologically active 1,25(OH)2 Vitamin D takes place into the cells and so requires the internalization of 25OH Vitamin D from the extracellular fluid. Different transport mechanisms are likely to be involved and some of them involve the concentration of the free ligand as one of the important parameters. In these cases the fraction of free 25OH Vitamin D relates to the biological activity of Vitamin D and therefore may better reflect the physiological action of Vitamin D than the total concentration of 25OH Vitamin D.
The fraction of free 25OH Vitamin D represents about 0.04% of the total concentration of 25OH Vitamin D. However this percentage is not constant and varies according to different conditions. Although the level of albumin tends to be stable amongst individuals the concentration of VDBP can fluctuate in several conditions, therefore influencing the fraction of free 25OH Vitamin D. In these conditions the measurement of free 25OH Vitamin D is thought to be a better marker of individual’s Vitamin D status than the routine measurement of total 25OH Vitamin D.
In addition to variable concentrations VDBP also exists as different polymorphic forms. The affinity of the different VDBP forms towards 25OH Vitamin D may vary although this is still under debate. A polymorphic form with a high affinity for 25OH Vitamin D will decrease the fraction of free 25OH Vitamin D available. Conversely, a low affinity VDBP form will result in higher levels of free 25OH Vitamin D. The major form of VDBP present in individuals depends on the ethnicity. E.g. among blacks the predominant form is Gc1F, while among whites, the predominant form is Gc1S. If the difference in affinity really exists, the measurement of free 25OH Vitamin D may again be a better marker of the Vitamin D action than the measurement of total 25OH Vitamin D.