25-OH-D (calcidiol)
The biomarker that reveals your true vitamin D reserves
Definition
25-hydroxyvitamin D, or calcidiol, is the circulating storage form of vitamin D and the reference biomarker used to assess whole-body vitamin D status on a blood panel. It is produced in the liver from cholecalciferol (D3) — synthesized in the skin or obtained from diet — and is later converted in the kidney into the active hormonal form, calcitriol. Unlike calcitriol, which is under tight homeostatic control with a half-life of hours, calcidiol stably reflects cumulative vitamin D supply, with a half-life of two to three weeks. This is precisely why clinical guidelines measure 25-OH-D, not calcitriol, to diagnose deficiency.
Detailed explanation
Metabolic pathway: cutaneous 7-dehydrocholesterol exposed to UVB radiation (or dietary vitamin D) yields cholecalciferol (D3), which travels to the liver bound to vitamin D binding protein (DBP). There the enzyme CYP2R1 hydroxylates it at position 25 to produce 25-OH-D (calcidiol). A second, renal step (CYP27B1) generates 1,25-OH-D (calcitriol), the active form that binds the VDR receptor.
Why calcidiol is measured instead of calcitriol: calcitriol has a half-life under 4 hours and is regulated so tightly by PTH, calcium and phosphate that it can remain normal even in overt deficiency — making it useless for assessing status. Calcidiol, with a half-life of roughly 2-3 weeks, integrates weeks of sun exposure and dietary intake, which makes it the reliable marker.
Interpretive thresholds (serum 25-OH-D): deficiency <20 ng/mL (<50 nmol/L), insufficiency 20-30 ng/mL, sufficiency 30-50 ng/mL, and a range widely regarded as optimal for longevity of 40-60 ng/mL. Chronic toxicity (>150 ng/mL) can cause hypercalcemia. The conversion is 1 ng/mL = 2.5 nmol/L. Factors that lower calcidiol include high latitude, winter, darker skin pigmentation, obesity (adipose sequestration), aging, malabsorption, and CYP2R1/DBP polymorphisms.
Scientific sources
- PubMed — Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline (Holick, JCEM 2011)
- PubMed — Pharmacokinetics of vitamin D toxicity (Jones, Am J Clin Nutr 2008)
- Source — Vitamin D — StatPearls, NCBI Bookshelf
- PubMed — Vitamin D for the Prevention of Disease: an Endocrine Society Clinical Practice Guideline (2024)
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