Vitamin D3

Category: vitamin

Aliases: Cholecalciferol, Vitamin D3, vit-d3, vitamin-d3, cholecalciferol

Pharmacological Mechanism

Cholecalciferol is the pro-hormone produced from 7-dehydrocholesterol by UVB in skin. Sequentially hydroxylated (see vitamin d metabolism) in liver (CYP2R1 → 25-OH-D / calcifediol) and kidney (CYP27B1 → 1,25-(OH)₂D / calcitriol, the active hormone). Calcitriol binds VDR to regulate ~500 genes controlling intestinal Ca²⁺ absorption, bone remodelling, and innate-immune LL-37 / CAMP expression. magnesium is a cofactor for both hydroxylation steps.

Half-Life (t½)

PO: 360h

Dosing Guidelines

PO: Typical 2333 IU (Range: 1000–5000 IU)

Target Organ Systems

endocrine
digestive
renal
musculoskeletal
integumentary
immune-hematologic

Interactions

Magnesium (synergistic): Bidirectional cofactor requirement.
Calcium (synergistic): D3 drives Ca absorption; their doses should rise together in bone-health stacks.
LL-37 (synergistic): D3 is the principal transcriptional driver of cathelicidin (CAMP gene) expression.
Orlistat (caution): Fat-soluble vitamin malabsorption — supplement.
Calcifediol (synergistic): Same pathway — calcifediol is the hepatic metabolite of D3. Generally pick one unless rapid 25(OH)D correction is needed.
Calcitriol (caution): Concomitant D3 can unmask hypercalcemia; use only under monitoring.
Vitamin D2 (synergistic): Same pathway; D3 is more efficient per IU at raising 25(OH)D. Generally pick one.
Menaquinone-4 (MK-4) (synergistic): D3 raises Ca²⁺ absorption; K2 directs deposition to bone vs. vasculature. Classic bone-health pair.
Menaquinone-7 (MK-7) (synergistic): Same bone-health directional synergy as MK-4.

Pathways It Modulates

Calcium / phosphate / PTH / vitamin D axis (substrate) — axis component (supports gut Ca absorption)
Klotho / FGF23 phosphate axis (substrate) — D₃ substrate; calcitriol drives FGF23 secretion (feedback)
TLR (Toll-like receptor) innate signaling (inhibitor) — TLR2/4 expression (vitamin D dampens innate)
Vitamin D activation cascade (substrate) — cascade entry (vitamin D3 supplementation)
Vitamin D receptor genomic signaling (VDR) (substrate) — D₃ substrate; needs 25-hydroxylation + 1α-hydroxylation
Wnt / β-catenin canonical signaling (inhibitor) — pro-VDR → Wnt cross-talk

Chemical Identifiers

PubChem CID: 5280795
Formula: C27H44O
Molecular weight: 384.64 g/mol
InChIKey: QYSXJUFSXHHAJI-YRZJJWOYSA-N
SMILES: C[C@H](CCCC(C)C)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](CCC3=C)O)C