calcifediol

Calcifediol, chemically 25-hydroxyvitamin D3 (25(OH)D3), is a vitamin D metabolite formed in the liver from cholecalciferol (vitamin D3) by the enzyme 25-hydroxylase. It is the major circulating form of vitamin D and is commonly measured to assess vitamin D status. A related metabolite, 25-hydroxyvitamin D2 (25(OH)D2), from ergocalciferol, contributes to total 25(OH)D.

Calcifediol is a prehormone, not the active form. It travels in the blood bound to vitamin D binding protein (DBP). In the kidney, 1α-hydroxylase converts calcifediol to calcitriol (1,25-dihydroxyvitamin D), the hormonally active form; extrarenal tissues can also perform 1α-hydroxylation in limited circumstances. Calcifediol has a relatively long circulating half-life, on the order of two to three weeks, which supports its use as a biomarker of vitamin D status.

Serum 25(OH)D concentration reflects vitamin D status from sun exposure, diet, and supplementation and is the standard measure because of its stability and long half-life. Units are ng/mL or nmol/L (1 ng/mL = 2.5 nmol/L). Deficiency definitions vary by organization, but commonly <20 ng/mL (50 nmol/L) is considered deficient, 20–30 ng/mL insufficient, and ≥30 ng/mL sufficient; some guidelines use higher thresholds.

Laboratory assays for 25(OH)D include immunoassays and liquid chromatography–tandem mass spectrometry (LC-MS/MS); results can vary between methods and require standardization. Measurement of calcifediol informs vitamin D status but does not diagnose disease, and interpretation should consider clinical context and risk factors.