Vitamin D3 (Cholecalciferol)
Cholecalciferol doesn't work as-is. It has to get converted twice: first to 25-hydroxyvitamin D, then to the active form, 1,25-dihydroxyvitamin D. That active form binds the nuclear vitamin D receptor and from there runs calcium and phosphate homeostasis, bone mineralization, and immune modulation. Fix a deficiency and you support musculoskeletal health directly. In older adults who were genuinely low, it can cut fall and fracture risk too.
Evidence
The observational studies keep saying the same thing: low 25(OH)D, higher all-cause mortality. Consistently. So of course everyone assumed supplementing would fix it. Then VITAL and D-Health, two large randomized trials, tested it directly and found no significant reduction in all-cause mortality, cardiovascular events, or cancer incidence in people who were already replete. The benefit lives in fixing a deficiency. It does not live in topping off someone who was never low to begin with.
Interactions
Thiazide diuretics plus vitamin D can raise calcium (hypercalcemia risk); may interact with digoxin via calcium. Corticosteroids, orlistat, and some anticonvulsants can lower vitamin D levels. Combine cautiously with high-dose calcium.
Cautions
Excess is stored (fat-soluble) and can cause hypercalcemia; do not exceed tolerable upper intake (4000 IU/day) without monitoring. Caution in sarcoidosis, granulomatous disease, and hyperparathyroidism. Test levels rather than mega-dosing blindly.
Food sources
Fatty fish, cod liver oil, egg yolk, UV-exposed mushrooms (D2), and fortified milk/plant milks and cereals; cutaneous synthesis from sunlight.
