Vitamin D (25-OH)

25-hydroxyvitamin D (25-OH-D, calcidiol) is the major circulating form of vitamin D and the standard clinical biomarker for assessing vitamin D status, produced in the liver by hydroxylation of cholecalciferol (D3) or ergocalciferol (D2). It reflects both dietary intake and skin synthesis from UVB exposure; its half-life of roughly 2–3 weeks makes it a reliable index of longer-term status compared with the active hormonal form 1,25-(OH)₂D. Deficiency (commonly defined as <50 nmol/L or <20 ng/mL) is associated with impaired bone mineralization, falls, increased susceptibility to respiratory infection, and observationally with higher all-cause and cardiovascular mortality, although randomized trials have shown mixed results for supplementation on hard outcomes. The 2024 Endocrine Society clinical practice guideline (Demay et al., JCEM) moved away from threshold-based deficiency definitions for asymptomatic adults — finding insufficient clinical-trial evidence to tie specific 25(OH)D cutoffs to outcomes — and recommended empiric supplementation for selected groups (<18 years, >75 years, pregnancy, high-risk prediabetes) rather than universal screening. Many longevity-oriented practitioners still target 75–100 nmol/L despite the guideline shift.