Vitamin D3

Vitamin D3 (cholecalciferol) is a fat-soluble secosteroid hormone precursor synthesized in the skin upon UVB exposure. Deficiency affects an estimated 1 billion people worldwide and is associated with increased risk of infections, autoimmune disease, osteoporosis, cardiovascular disease, depression, and cancer. It functions more like a hormone than a traditional vitamin, regulating over 1,000 genes.

Converted in the liver to 25(OH)D (calcidiol, the storage form measured in blood tests), then in the kidneys to 1,25(OH)₂D (calcitriol, the active hormone). Calcitriol binds the Vitamin D Receptor (VDR) present in nearly every tissue, regulating gene expression. Enhances calcium absorption (gut), promotes bone mineralization, activates innate immune defenses (cathelicidin/LL-37 production), modulates T-cell and B-cell function, and suppresses excessive inflammatory responses.

Cholecalciferol: half-life approximately 15 days. 25(OH)D (storage form): half-life approximately 2–3 weeks. Calcitriol (active form): half-life approximately 4–6 hours. Peak blood levels of supplemental D3 reached in 12–24 hours. Steady-state 25(OH)D levels reached in 3–4 months of consistent dosing.

Bone health and osteoporosis prevention, immune system modulation, infectious disease resistance (COVID-19, respiratory infections), cancer prevention, cardiovascular health, depression and mood, autoimmune disease.

Essential nutrient with FDA Daily Value established. Extensively studied in RCTs for multiple indications. VITAL trial (25,000+ participants) tested cancer and cardiovascular prevention. Endocrine Society recommends 1,500–2,000 IU daily for adults. Target 25(OH)D: 30–60 ng/mL.

• Vitamin D — MedlinePlus · medlineplus.gov
• VITAL trial — Vitamin D and health outcomes — NEJM · doi.org
• Vitamin D and immune function — BMJ · doi.org
• Vitamin D pharmacokinetics review · doi.org