Vitamin D, 25-hydroxy [25(OH)D], is the main circulating storage form of vitamin D. It integrates sun exposure, intake, and liver conversion, and supplies the kidney to make the active hormone calcitriol. Adequate 25(OH)D supports calcium–phosphate balance, bone and tooth mineralization, muscle performance, vascular and insulin signaling, immune modulation, and aspects of reproduction and cognition.Low values usually reflect limited skin synthesis, low intake or absorption, sequestration in adipose tissue, or impaired liver/kidney conversion. Physiology shifts to reduced intestinal calcium uptake, compensatory rise in parathyroid hormone, and bone resorption, leading to poor mineralization (osteomalacia; rickets in children) and proximal muscle weakness with falls. Older adults and people with darker skin are more affected; in pregnancy, fetal skeletal mineralization may be constrained.Being in range suggests adequate substrate for calcitriol, stable calcium–phosphate homeostasis, normal parathyroid tone, efficient bone turnover and muscle function, and balanced innate and adaptive immune signaling. Many groups consider mid-range values sufficient; higher-than-mid values do not consistently add benefit.High values usually reflect excessive supplementation or, less often, extrarenal activation in granulomatous disease or lymphoma. Physiology favors hypercalcemia and hypercalciuria, with thirst, nausea, weakness, arrhythmias, kidney stones, and soft‑tissue calcification. Infants and pregnant individuals are more susceptible to calcium-related effects.Notes: Season, latitude, skin pigmentation, age, adiposity, and acute illness influence levels. Estrogens and pregnancy raise vitamin D–binding protein, altering total concentrations. Anticonvulsants, rifampin, and glucocorticoids accelerate catabolism. Chronic liver or kidney disease reduces conversion. Assay methods vary; LC‑MS/MS is most specific, and lab reference intervals differ.
