Notably, in vivo treatment with 1,25(OH)2D3 is associated with increased metabolic clearance of 25(OH)D3, decreased serum 25(OH)D3 levels, and a higher 25(OH)D3 to 24,25(OH)2D3 conversion rate in humans and animals. This suggests that use of 25(OH)D as single biomarker of vitamin D status does not fully capture the entire picture. Paradoxically, one individual may be classified with 'low' 25(OH)D as a consequence of low dietary intake and little sun exposure while yet another individual classified with 'low' 25(OH)D may actually have a higher concentration of the 1,25(OH)2D3 metabolite—possibly due to genetic differences in enzymes that metabolize vitamin D (CYP2R1, CYP27B1, and CYP24A1).