CalcidiolEdit
Calcidiol, more formally known as 25-hydroxyvitamin D, is the principal circulating form of vitamin D and the field standard for assessing an individual’s vitamin D status. It is produced in the liver by hydroxylation of vitamin D obtained from sun exposure, diet, or supplements. Although calcidiol reflects overall vitamin D stores, it is not the active hormone itself; that role belongs to calcitriol (1,25-dihydroxyvitamin D), which is generated primarily in the kidneys and other tissues in response to hormonal signaling. In clinical practice, measuring calcidiol levels provides a practical proxy for how much vitamin D is available to the body for bone and other physiologic functions. Vitamin D 25-hydroxyvitamin D Liver Kidney
Calcidiol as a circulating reservoir is bound predominantly to vitamin D binding protein and, to a lesser extent, to albumin. Its half-life is measured in weeks, making it a useful indicator of longer-term vitamin D status rather than short-term fluctuations. Because calcidiol integrates input from sun exposure, dietary intake, and supplementation, it serves as a composite biomarker that clinicians use to gauge risk for bone diseases such as osteomalacia in adults and rickets in children, as well as for broader aspects of calcium and phosphorus metabolism regulated by the vitamin D axis. The active hormone calcitriol exerts rapid, local effects in target tissues through the vitamin D receptor, but calcidiol itself acts mainly as a stored pool that can be converted when conditions require. Calcitriol Parathyroid hormone Bone Calcium Phosphate
Biochemistry and physiology
Calcidiol is produced in the liver through the action of enzymes such as 25-hydroxylase on vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol). The resulting 25-hydroxyvitamin D circulates bound to vitamin D binding protein and can be taken up by various organs where it may be further hydroxylated to calcitriol by 1α-hydroxylase, most prominently in the kidney but also in other tissues under specific conditions. Calcitriol then modulates intestinal calcium and phosphate absorption, bone mineralization, and other metabolic processes through the vitamin D receptor. Because calcidiol levels are influenced by sun exposure, diet, skin pigmentation, age, body mass, and liver function, interpretation must consider both lifestyle and medical context. Liver Kidney Vitamin D receptor Ultraviolet radiation Lipid-soluble vitamins
Measurement of calcidiol is typically performed by blood tests using immunoassays or more precise chromatographic methods such as liquid chromatography–tandem mass spectrometry. Results are commonly reported in nanograms per milliliter (ng/mL) or nanomoles per liter (nmol/L). While there is broad agreement that very low calcidiol levels are associated with bone problems, the exact cutpoints for deficiency, sufficiency, and optimal health vary among professional societies, reflecting ongoing debate about how high calcidiol should be for non-skeletal benefits and how to balance individual risk with public health goals. 25-hydroxyvitamin D Hypervitaminosis D Osteomalacia Osteoporosis
Sources, storage, and variability
Sunlight is a major natural source of vitamin D, as ultraviolet B (UVB) radiation converts 7-dehydrocholesterol in the skin to previtamin D3 and then to vitamin D3. Factors such as latitude, season, time outdoors, sunscreen use, and skin pigmentation influence the amount of vitamin D synthesized. People with darker skin colors (in general) require longer sun exposure to achieve the same production of vitamin D as people with lighter skin, all else being equal. Dietary sources contribute modestly in most populations, with fatty fish, cod liver oil, egg yolks, and fortified foods playing supporting roles. Fortification programs and voluntary supplementation help maintain calcidiol levels in populations where sun exposure or dietary intake is insufficient. Sunscreen Ultraviolet radiation Fortification (food) Diet Fat-soluble vitamins Vitamin D
Population-level guidance on sun exposure and supplementation aims to prevent bone disease while minimizing risks such as skin cancer, but the policy landscape is constantly debated. Some argue for targeted supplementation and testing in at‑risk groups (the elderly, individuals with malabsorption, or certain medical conditions) rather than broad, routine screening, which can drive costs without proportional health gains. Others advocate more aggressive fortification and screening as a public health measure. Osteoporosis Osteomalacia Vitamin D deficiency Public health policy
Measurement, interpretation, and clinical relevance
Calcidiol interpretation depends on the context. Low levels correlate with increased risk of bone demineralization and fractures, particularly in older adults, and can signal inadequate calcium absorption or insufficient sun exposure. Adequate calcidiol levels support bone health and may contribute to immune and muscular function, though evidence for non-skeletal benefits remains mixed and is a subject of ongoing research and debate. In clinical practice, determining whether a patient should begin or adjust vitamin D supplementation involves reviewing dietary intake, sun exposure, liver and kidney function, obesity (which can lower circulating calcidiol due to sequestration in adipose tissue), and potential drug interactions that affect vitamin D metabolism. Osteoporosis Rickets Calcitriol Liver Kidney Parathyroid hormone
Controversies in the field include how to define “adequate” calcidiol, whether universal screening is cost-effective, and how aggressively to pursue fortification versus targeted supplementation. Skeptics of broad public-health campaigns argue that personal responsibility and sensible supplementation guidelines can achieve most health goals without expanding governmental mandates or distorting markets. Proponents counter that well-designed fortification and screening programs can reduce disparities in vitamin D status and prevent costly bone and metabolic problems, particularly among vulnerable populations. In this debate, some critics insist that emphasis on structural or societal factors should not overshadow straightforward medical guidance, while others contend that policies should reflect broader social considerations. Critics of what they view as excessive emphasis on systemic causes sometimes frame vitamin D status as primarily a matter of lifestyle and access to sunlight, a stance that, from their perspective, prioritizes practical solutions over expansive social theory. Fortification (food) Vitamin D deficiency Public health policy Endocrine Society