Cutaneous vitamin D synthesis

Step 1 — skin. 7-Dehydrocholesterol in the plasma membranes of keratinocytes of the stratum basale and spinosum absorbs UVB (≈290–315 nm), opening its B ring to form previtamin D3, which isomerises over hours at body temperature to vitamin D3 (cholecalciferol). This diffuses into dermal capillaries bound to vitamin D-binding protein. Continued UV exposure converts surplus previtamin D3 into biologically inert lumisterol and tachysterol, so sunlight never causes vitamin D intoxication. Dietary vitamin D2 (ergocalciferol) and D3 enter the same pathway.

Step 2 — liver. 25-Hydroxylase (CYP2R1) forms 25-hydroxyvitamin D (calcidiol), the main circulating form (half-life ≈2–3 weeks) and the best laboratory measure of vitamin D status.

Step 3 — kidney. In the proximal tubule, 1α-hydroxylase (CYP27B1) forms the active hormone 1,25-dihydroxyvitamin D (calcitriol). This step is tightly regulated: stimulated by PTH, hypocalcaemia and hypophosphataemia; inhibited by FGF23 and calcitriol itself. Calcitriol increases intestinal calcium and phosphate absorption, promotes bone mineralisation and acts with PTH on bone and kidney. Keratinocytes also express 1α-hydroxylase, producing calcitriol locally to regulate their own differentiation and innate immunity (cathelicidin induction).

Synthesis is reduced by dark skin pigmentation (melanin competes for UVB), high latitude and winter (low solar angle), sunscreen, clothing, air pollution, obesity (sequestration in fat) and ageing (less 7-dehydrocholesterol).