Cholecalciferol

CAS No:	67-97-0
EINECS No:	200-673-2
Synonyms:	Activated 7-dehydrocholesterol, calciol, colecalciferol, (3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-3-ol, Vit D3

Product Summary

Cholecalciferol (vitamin D₃) is a lipophilic prohormone (C₂₇H₄₄O, 384.64 g/mol) typically produced by UV conversion of lanolin-derived 7-dehydrocholesterol. After metabolic activation to calcitriol, it binds VDR to regulate genes controlling calcium absorption, bone health, and diverse extra-skeletal pathways. In research, it’s used from basic VDR signaling studies to nutrition, immunology, oncology, and analytical assay development. Because it is highly light/oxygen-sensitive, store it cold in amber, airtight containers, under inert gas when possible, and prepare protected aliquots for consistent activity.

Function

Cholecalciferol is a prohormone that maintains calcium–phosphate homeostasis and supports bone mineralization, neuromuscular function, and many extra-skeletal processes via the vitamin D endocrine system.

Mechanism of Action

The activity mechanism of cholecalciferol involves a multi-step activation process and genomic/non-genomic actions to regulate calcium-phospohorus homeostasis, bone health, and other physiological functions:

Synthesis and activation
Cholecalciferol is synthesized in the skin when 7-dehydrocholesterol reacts with UVB radiation. Inactive cholecalciferol is transported to the liver, where 25-hydroxylase (CYP2R1/CYP27A1) converts it to 25-hydroxycholecalciferol (calcifediol, 25(OH)₃D₃). In kidney proximal tubules, 1α-hydroxylase (CYP27B1) further hydroxylates 25(OH)₃D₃ to 1,25-dihydroxycholecalciferol (calcitriol; 1,25(OH)₂D₃).
Genomic pathway
Calcitriol binds the vitamin D receptor (VDR), a ligand-activated nuclear receptor that heterodimerizes with RXR and binds VDREs in DNA to regulate transcription. The key outcomes include upregulating intestinal calcium transporters (e.g., TRPV6, calbindin-D), promoting bone remodeling/mineralization, modulating PTH, and exerting immunomodulatory and anti-proliferative/differentiation effects in various cell types.
Non-genomic actions
Rapid membrane-associated effects (e.g., activation of protein kinases) for acute calcium flux.
Feedback control
Calcitriol inhibits CYP27B1 in kidney and induces CYP24A1, promoting its own degradation to inactive forms.

Applications in Scientific Research

Bone & mineral metabolism: Models of rickets/osteoporosis; osteoblast/osteoclast gene programs; calcium absorption studies.
Endocrinology & renal research: PTH–vitamin D axis; CKD-MBD (mineral bone disorder) pathways; regulation of CYP27B1/CYP24A1.
Immunology: VDR-mediated modulation of innate/adaptive responses; macrophage/monocyte function; autoimmune disease models.
Oncology & cell biology: VDR signaling in cell cycle control, differentiation, EMT; studies of calcitriol analogs with reduced calcemic liability.
Cardiometabolic & neurology: Investigations into cardiometabolic markers, insulin signaling, neurodevelopment/neuromodulation (preclinical/observational).
Dermatology/photobiology: UV-B synthesis pathways; keratinocyte biology; barrier function.
Nutrition & fortification science: Bioavailability from different matrices; microencapsulation, nanoemulsions, lipid carriers.
Analytical chemistry: Reference standard in LC-MS/MS assays for serum 25(OH)D quantification and stability/photolysis studies.
Toxicology/High-dose studies: Hypervitaminosis D mechanisms (hypercalcemia, soft-tissue calcification) and, at very high doses, its historical use as a rodenticide active—handled under appropriate controls.

Packaging & Storage

Sources: Photochemical conversion of 7-dehydrocholesterol derived from lanolin (sheep wool grease)
White to off-white crystalline powder
Storage: at room temperature, protect from light and moisture

References

Cashman KD, et al. 2012: Relative effectiveness of oral 25-hydroxyvitamin D₃ and vitamin D₃ in raising wintertime serum 25-hydroxyvitamin D in older adults, Am J Clin Nutr. 95(6): 1350-6.
Heaney RP, et al. 2003: Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol, Am J Clin Nutr. 77(1): 204-10.
Tripkovic L, et al. 2012: Comparison of vitamin D₂ and vitamin D₃ supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis, Am J Clin Nutr. 95(6): 1357-64.
Sosa Henríquez M, et al. 2020: Cholecalciferol or calcifediol in the management of vitamin D deficiency, Nutrients. 12(6): 1617.
Alshahawey M, et al. 2021: The impact of cholecalciferol on markers of vascular calcification in hemodialysis patients: A randomized placebo controlled study, Nutr Metab Cardiovasc Dis. 1(2): 626-633.
Reynolds NA, Curran MP. 2005: Alendronate/colecalciferol, Treat Endocrinol. 4(6): 371-7.
Kuznia S, et al. 2023: Efficacy of vitamin D₃ supplementation on cancer mortality: Systematic review and individual patient data meta-analysis of randomised controlled trials, Ageing Res Rev. 87: 101923.
Oluwole DT, Ajayi AF. 2025: Vitamin D₃, cholecalciferol via its hydroxylmetabolites, receptors and metabolizing enzymes modulates male reproductive functions, Life Sci. 373: 123680.
Dzavakwa NV, et al. 2024: Update: Vitamin D₃ and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial, Trials. 25(1): 499.
Swierczyński J, et al. 1987: Calcium content in some organs of rats treated with a toxic calciol dosis, Pharmacology. 34(1): 57-60.
Asfour MH, et al. 2023: Vitamin D₃-loaded nanoemulsions as a potential drug delivery system for autistic children: Formulation development, safety, and pharmacokinetic studies, AAPS PharmSciTech. 24(2): 58.
Christakos S, et al. 2016: Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects, Physiol Rev. 96(1): 365-408.
Pike JW, Christakos S. 2017: Biology and mechanisms of action of the vitamin D hormone, Endocrinol Metab Clin North Am. 46(4): 815-843.