Cholecalciferol
Properties
| State | Solid (white to yellowish crystalline powder) |
| Color | White to yellowish |
| Solubility | Insoluble in water; soluble in ethanol, acetone, ether, and fats/oils |
| Melting Point | 83-86°C |
| Boiling Point | Decomposes before boiling |
About Cholecalciferol
Cholecalciferol is a secosteroid — a steroid where one of the rings has been broken open — and the broken ring (the B ring of the parent cholesterol skeleton) is what makes it a vitamin D rather than a regular steroid. The biosynthesis runs in your skin: 7-dehydrocholesterol absorbs a UVB photon between 290 and 315 nm, the B ring undergoes a six-electron pericyclic ring-opening to give pre-vitamin D3, and that thermally isomerizes over the next few hours to cholecalciferol via a [1,7]-sigmatropic hydrogen shift. The product itself is hormonally inactive — it has to be hydroxylated twice to do anything. The first hydroxylation runs in the liver via CYP2R1 and CYP27A1 to give 25-hydroxyvitamin D (calcidiol), which is the metabolite measured in your blood test because it has a half-life of about three weeks and reflects long-term status. The second hydroxylation runs in the kidney via CYP27B1 under tight PTH and FGF23 control to give 1,25-dihydroxyvitamin D (calcitriol), which is the actual hormone. Calcitriol binds the vitamin D receptor (a nuclear hormone receptor in the same family as the thyroid and retinoic acid receptors), heterodimerizes with RXR, and activates transcription of calcium-binding protein, the epithelial Ca2+ channel TRPV6, and a few hundred other genes that handle Ca2+ and phosphate handling. Deficiency gives rickets in kids and osteomalacia in adults — soft bones — and remained a major public health problem in northern latitudes until milk fortification rolled out in the US starting in the 1930s.
Where you'll encounter it
If you've ever had a 25-OH vitamin D blood test come back below 30 ng/mL, the supplement your doctor handed you is cholecalciferol, almost always made by UV-irradiating 7-dehydrocholesterol extracted from sheep's wool lanolin. The lanolin connection is why D3 is technically not vegan — the vegan alternative is ergocalciferol (D2) made by UV-irradiating ergosterol from yeast, but D2 raises serum 25-OH-D less efficiently than D3 at the same dose. In a clinical lab, the LC-MS/MS method for measuring 25-OH-D simultaneously quantifies the D2 and D3 forms and reports total — important because vegan patients on D2 supplements can look deficient on assays that don't distinguish.
Common Uses
- Oral supplement for treating and preventing 25-OH-D deficiency at doses from 600 to 50,000 IU per dose
- Fortification of milk, breakfast cereals, orange juice, and infant formula to public health targets
- Treatment for nutritional rickets in children and osteomalacia in adults at prescription doses
- Adjunctive therapy for chronic kidney disease patients alongside calcium and phosphate management
- Veterinary feed additive for poultry, swine, and dairy cattle to prevent rickets and milk fever
- Reference compound in LC-MS/MS clinical assays for serum 25-hydroxyvitamin D quantification
- Active ingredient in some rodenticides (very high doses cause fatal hypercalcemia in rodents)
- Research substrate for studying vitamin D receptor-mediated transcriptional regulation
Safety Information
Acute toxicity from a single dose is essentially impossible at supplement levels — the LD50 in rats is around 42 mg/kg, which would be roughly 3 grams in an adult human, equivalent to 120 million IU. Chronic supplementation above 10,000 IU/day eventually causes hypervitaminosis D: serum 25-OH-D climbs above 150 ng/mL, calcitriol-driven calcium absorption pushes serum calcium above 11 mg/dL, and you get nausea, polyuria, kidney stones, and metastatic calcification of soft tissues including the kidneys and arteries. The Tolerable Upper Intake Level set by the IOM is 4000 IU/day for adults, with a no-observed-adverse-effect level around 10,000 IU/day. Sun exposure cannot cause toxicity because previtamin D3 photoisomerizes to inactive lumisterol and tachysterol once skin levels saturate — the skin self-regulates. The OSHA-relevant occupational hazard is dust exposure during pharmaceutical manufacturing; the manufacturing limit is typically set at 0.1 mg/m3.
This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.