25Hydroxyvitamin

25-hydroxyvitamin D, commonly referred to as 25(OH)D and also called calcidiol, is a prehormone produced in the liver by hydroxylation of vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). It is the major circulating form of vitamin D and serves as the best overall indicator of vitamin D status in the body.

Biochemical role and metabolism: In the liver, enzymes such as CYP2R1 and CYP27A1 add a hydroxyl group at the 25 position to cholecalciferol or ergocalciferol, yielding 25(OH)D. This circulating form binds predominantly to vitamin D–binding protein and has a relatively long half-life, enabling it to reflect vitamin D input from skin synthesis and diet. A smaller pool remains free or loosely bound. 25(OH)D can be further hydroxylated in the kidney and other tissues by 1α-hydroxylase to form the hormonally active 1,25-dihydroxyvitamin D.

Clinical use and interpretation: Serum 25(OH)D measurement is used to assess vitamin D status. Assays include immunoassays and LC-MS/MS, with results reported in ng/mL or nmol/L. Typical thresholds vary by guideline, but commonly ≥30 ng/mL (75 nmol/L) is cited as sufficient, 20–29 ng/mL as insufficient, and <20 ng/mL as deficient. Values can be influenced by assay type and population.

Health relevance: Adequate 25(OH)D supports calcium and phosphate homeostasis and bone health, reducing risks of rickets in children and osteomalacia in adults. Observational links with other health outcomes exist, but causality and benefits of supplementation beyond deficiency are still under study.