Vitamin D

Vitamin D is a fat-soluble prohormone with receptors in virtually every tissue, supporting calcium and phosphate homeostasis, immune regulation, neuromuscular function, and gene expression. Endogenous production requires UVB exposure to 7-dehydrocholesterol in skin, producing vitamin D3 (cholecalciferol), which then undergoes hepatic hydroxylation to 25-hydroxyvitamin D (the status marker) and renal activation to 1,25-dihydroxyvitamin D (the active hormone).

Deficiency is widespread globally and particularly in higher latitudes or populations with limited sun exposure. Evidence supports target 25-hydroxyvitamin D levels between 30 and 60 ng/mL (75-150 nmol/L) for skeletal and most extraskeletal indications. Associations with depression (Anglin et al., 2013), ADHD (6.55 ng/mL lower in ADHD cohorts, 2025 meta-analysis), autoimmune disease risk, and all-cause mortality support repletion when deficiency is documented. However, vitamin D supplementation in already-replete individuals shows minimal benefit in most outcomes.

Supplementation with D3 (cholecalciferol) at 2000-4000 IU daily is appropriate for most adults with deficiency and is safe without monitoring in healthy adults. Higher doses (5000-10,000 IU) may be needed for severe deficiency or malabsorption and should be accompanied by repeat testing at 3 months. Cofactor sufficiency matters: magnesium is required for vitamin D activation, and vitamin K2 (MK-7, 100-200mcg) directs calcium to bone rather than arterial tissue. Intramuscular or high-dose bolus dosing (300,000 IU or more) is associated with falls and fractures in some populations and should be avoided in favor of daily or weekly oral dosing.