Vitamin D3 — The Sunshine Hormone
Vitamin D3 (cholecalciferol) is a secosteroid hormone with receptors in virtually every cell type. Deficiency affects ~40% of adults globally and is associated with increased all-cause mortality, cardiovascular disease, cancer, and immune dysfunction.
Mechanism of Action
Vitamin D3 is hydroxylated in the liver to 25(OH)D3 and then in the kidney to the active form 1,25(OH)2D3 (calcitriol). Calcitriol binds the vitamin D receptor (VDR) to regulate >1,000 genes involved in immune modulation, calcium homeostasis, cell proliferation, and inflammation. It also activates telomerase.
Human Trial Evidence
4,120+ trials. The VITAL trial (2019, NEJM, n=25,871) showed vitamin D3 (2,000 IU/day) reduced cancer mortality by 25% and cardiovascular events in people with low BMI. A 2014 BMJ meta-analysis of 26 cohorts showed low 25(OH)D was associated with 1.57× higher all-cause mortality.
Dosing Protocol
2,000–4,000 IU/day for most adults. Optimal serum 25(OH)D: 40–60 ng/mL. Test before supplementing — some individuals need 5,000–10,000 IU/day to reach optimal levels. Always take with Vitamin K2 MK-7 (prevents soft tissue calcification). Take with fat for absorption.
Safety & Contraindications
Toxicity (hypercalcemia) only occurs at sustained doses >10,000 IU/day for months. At 4,000 IU/day, no toxicity in healthy adults. Monitor 25(OH)D levels annually. Vitamin D increases calcium absorption — ensure adequate hydration.