Vitamin D3
Cholecalciferol - the form made from sunlight and found in animal sources. Converted to calcitriol, regulating calcium and thousands of genes.
Vitamin D3 (cholecalciferol) is a fat-soluble secosteroid made in skin from 7-dehydrocholesterol via UVB exposure, or obtained from animal-source foods. It is converted to the active hormone calcitriol, which regulates calcium homeostasis and thousands of genes.
Vitamin D metabolism: Skin synthesis or dietary D3 → Calcidiol/25(OH)D (in liver, via CYP2R1) - this is measured for status → Calcitriol/1,25(OH)2D (in kidney via CYP27B1, also in many tissues) - active hormone. The final step is tightly regulated by PTH, calcium, phosphorus, and FGF23.
Functions: Calcium and phosphorus absorption (intestine), Bone health (mineralization, prevents rickets/osteomalacia), Immune function (innate immunity, antimicrobial peptides, immune regulation), Muscle function, Insulin secretion, Blood pressure regulation, Cell differentiation (anti-cancer effects), and Brain function.
Deficiency is pandemic: Estimated 40-75% of people are insufficient.
Risk factors: dark skin, high latitude, indoor lifestyle, obesity (vitamin D trapped in fat), aging, malabsorption, and certain medications. Deficiency consequences: Rickets/osteomalacia, Osteoporosis, Increased infections, Autoimmune disease risk, Muscle weakness, Depression, and Increased cancer risk.
Testing: 25(OH)D is the best indicator. Optimal range is debated: deficient <20 ng/mL, insufficient 20-30 ng/mL, optimal likely 40-60 ng/mL for most people, potential toxicity >100 ng/mL. Supplementation: D3 (not D2) is preferred. Typical doses: 1000-5000 IU daily for maintenance.
Higher doses for deficiency. Take with fat for absorption. Cofactors needed: magnesium (for activation), vitamin K2 (directs calcium to bones), vitamin A (VDR partner).
Metabolic Connections
Vitamin D3 connects to 15 other pathways.
Major Minerals
Calcium
Vitamin D3 promotes intestinal calcium absorption and regulates calcium homeostasis
Most abundant mineral in the body. Essential for bones, muscle contraction, nerve signaling, and blood clotting.
Calcium
Vitamin D3 is essential for intestinal calcium absorption and calcium homeostasis
Most abundant mineral in the body. Essential for bones, muscle contraction, nerve signaling, and blood clotting.
Magnesium
Magnesium is required for converting vitamin D to its active form
Essential mineral involved in 300+ enzymatic reactions. Required for ATP, muscle/nerve function, and blood pressure regulation.
Magnesium
Magnesium is required for vitamin D metabolism and activation
Essential mineral involved in 300+ enzymatic reactions. Required for ATP, muscle/nerve function, and blood pressure regulation.
Processes
Immune Function
Vitamin D activates immune cells and promotes antimicrobial peptide production
The body's defense system against pathogens. Requires zinc, vitamins A/C/D, and proper balance to avoid autoimmunity.
Inflammation
Vitamin D has anti-inflammatory and immunomodulatory effects
Immune response to injury or infection. Acute inflammation heals; chronic inflammation drives disease.
Environmental
Sunlight
UVB radiation from sunlight synthesizes vitamin D3 in the skin
Essential for vitamin D synthesis, circadian rhythm regulation, and nitric oxide release. Impacts mood, immunity, and sleep.
Sunlight
UVB from sunlight converts 7-dehydrocholesterol in skin to vitamin D3
Essential for vitamin D synthesis, circadian rhythm regulation, and nitric oxide release. Impacts mood, immunity, and sleep.
Genes
Vitamin D Receptor (VDR)
Active vitamin D binds VDR to regulate gene expression
Nuclear receptor through which vitamin D exerts its effects on gene expression. Genetic variants affect vitamin D sensitivity.
Vitamin D Receptor (VDR)
VDR is the nuclear receptor through which vitamin D exerts its gene regulatory effects
Nuclear receptor through which vitamin D exerts its effects on gene expression. Genetic variants affect vitamin D sensitivity.
Nutrients
Vitamin K2
K2 activates proteins that direct vitamin D-induced calcium to bones, not arteries
Menaquinone - activates proteins that direct calcium to bones and away from arteries. Works synergistically with vitamin D3.
Vitamin K2
K2 directs vitamin D-induced calcium to bones and away from arteries
Menaquinone - activates proteins that direct calcium to bones and away from arteries. Works synergistically with vitamin D3.