Vitamin D is an essential fat-soluble vitamin that plays a crucial role in maintaining bone health, regulating calcium and phosphate balance, and supporting immune function. Vitamin D deficiency is one of the most common nutritional deficiencies worldwide and can have significant clinical consequences if left untreated. This article discusses the different forms of vitamin D and their pharmacology, including cholecalciferol, ergocalciferol, and alfacalcidol. It also explores the pharmacokinetics of vitamin D, routes of supplementation, indications for use, causes and risk factors for deficiency, and important cautions associated with vitamin D therapy. Mechanism of Action Vitamin D is available as several different analogues; cholecalciferol (vitamin D3) is synthesised by the skin in the presence of sunlight and represents approximately 80-90% of vitamin D production in people in the UK. Ergocalciferol (vitamin D2) is provided mainly through plant based diet. Both vitamin D3 and D2 circulate in the blood. Alfacalcidol is a synthetic prodrug of vitamin D which is converted to the active metabolite, calcitriol, in the liver. Calcidiol is the primary storage form of vitamin D3, and the active metabolite, calcitriol, circulates in the blood, bound to a specific α-globin known as vitamin D-binding protein (DBP). Calcitriol is the active metabolite which acts on the vitamin D receptor (VDR) which is a nuclear receptor, to modulate gene transcription, playing a vital role in bone formation, regulation of calcium and phosphate metabolism and modulation of the immune system. Created in BioRender. Boucher, M. (2026) https://BioRender.com/2ssaitt Fig 1: Biochemistry of Vitamin D Pharmacokinetics Oral Vitamin D Vitamin D is a fat-soluble vitamin and is absorbed alongside bile salts and dietary lipids, therefore oral absorption may be reduced in obstructive liver disease due to a reduction in bile salts. Furthermore, vitamin D absorption is increased when given alongside fatty foods. Patients with intestinal failure may also experience malabsorption of oral vitamin D. Vitamin D analogues are generally well absorbed orally. Cholecalciferol has a half life of ~50 days, whereas the half-life of alfacalcidol is ~4 hours. Alternative Routes of Supplementation A systematic review found buccal vitamin D spray to be an effective alternative to oral vitamin D supplements; however, buccal sprays are not currently regulated or licensed as medicines in the UK. Intramuscular ergocalciferol is also available for supplementation where the oral route is not available. After administration of intramuscular ergocalciferol, maximal hypercalcaemia effects occur at ~ 4 weeks. Indications for Use Vitamin D should be supplemented in patients whom are found to be deficient, and in conditions such as in osteoporosis, pregnancy, breastfeeding and chronic kidney disease (CKD). Vitamin D is often given alongside calcium in osteoporosis and CKD. Topical vitamin D analogues such as calcitriol and calcipotriol can be used to treat psoriasis. Osteoporosis In osteoporosis, vitamin D supplementation helps to restore calcium balance, doses of 400-800 units of vitamin D daily are often used. More information can be found in the corresponding article on osteoporosis. Chronic Kidney Disease In CKD there is reduced activation of vitamin D in the kidney, which can lead to hyperphosphataemia and hypocalcaemia, stimulating secondary hyperparathyroidism, where excess parathyroid hormone (PTH) is released to maintain normal calcium levels. Alfacalcidol is often used in CKD as it does not require activation by the kidneys. Adobe stock: 1781917095 Fig 2: Parathyroid hormone and calcium regulation Vitamin D Deficiency In vitamin D deficiency, a loading dose of vitamin D is often provided over a course of weeks or months. A vitamin D deficiency is diagnosed using the following serum total calcidiol (25-hydroxyvitamin D) concentrations: Total calcidiol level <25nmol/L – increased risk of vitamin D deficiency Total calcidiol level 25-50nmol/L – insufficient vitamin D level in some people (e.g. high risk patients with osteoporosis) Total calcidiol level >50nmol/L – sufficient for most people There are certain risk factors that increase the likelihood of vitamin D deficiency Age > 65years Reduced sunlight exposure Darker skin pigmentation Malabsorption e.g. intestinal failure or gastric bypass surgery CKD Pregnant and/or breastfeeding Obesity Patients taking anticonvulsants such as phenytoin, phenobarbital, sodium valproate and carbamazepine, due to induction of CYP450 enzymes (apart from sodium valproate, for which the mechanism remains unclear) and an increased metabolism and clearance of vitamin D Cautions Vitamin D supplementation should be avoided in hypercalcaemia, as excessive intake can worsen hypercalcaemia. Hypercalcaemia alongside hyperphosphataemia can lead to calcium salt deposition in the kidneys, resulting in renal failure and nephrolithiasis (kidney stones). Vitamin D3 (cholecalciferol) is often derived from animal fats, whereas vitamin D2 (ergocalciferol) is from plant sources, this should be considered if providing vitamin D supplementation to patients with dietary restrictions. References Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan DJ. Rang & Dale’s Pharmacology. 9th ed. London: Elsevier; 2019. Hitchings BSc, M., Lons BSc, M., Lonsdale, D., Burrage, D., Baker, E. (2022). The Top 100 Drugs – E-Book. Netherlands: Elsevier. Vitamin D deficiency in adults | Health topics A to Z | CKS | NICE Accessed 26/06/26 Pritchard, L., Hickson, M. and Lewis, S. (2020). Comparative effectiveness of vitamin D supplementation via buccal spray versus oral supplements on 25(OH)D concentrations: a systematic review. Proceedings of the Nutrition Society, 79(OCE2). doi:https://doi.org/10.1017/s0029665120006096. Colecalciferol 1 000 IU Capsules – Summary of Product Characteristics (SmPC) – (emc) | 7247 Accessed 26/6/26 Ergocalciferol 300,000IU Solution for Injection – Summary of Product Characteristics (SmPC) – (emc) | 9133 Accessed 26/6/26 Alfacalcidol 0.25 microgram soft capsules – Summary of Product Characteristics (SmPC) – (emc) | 14383 Accessed 26/6/26 Do you think you’re ready? Take the quiz below Pro Feature - Quiz Vitamin D Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 200 multiple-choice questions to reinforce learning. Learn More Rate This Article