Vitamin D

What it is

Vitamin D₃ (cholecalciferol) is synthesised in skin from 7-dehydrocholesterol on UVB exposure, then hydroxylated to 25(OH)D (circulating form) and 1,25(OH)₂D (active hormone). It regulates intestinal calcium absorption, bone remodelling, and immune function.

What the evidence shows

• Bone: replacement in deficiency prevents osteomalacia; adequate vitamin D and calcium reduce fracture risk in older adults.
• Cardiovascular and cancer: VITAL and DO-HEALTH trials in largely-replete populations showed no benefit of routine supplementation for cardiovascular events, cancer incidence, or healthspan composite endpoints.
• Immune / respiratory infections: meta-analyses suggest small benefit in deficient individuals; little in replete ones.
• Autoimmune disease: VITAL secondary analysis showed reduced autoimmune-disease incidence over 5 years.

Who benefits most

Adults with measured 25(OH)D <50 nmol/L (~20 ng/mL), particularly older, darker-skinned, or sun-deprived. For everyone else, supplementation is unlikely to produce hard-endpoint benefit.

Practical use

• Test 25(OH)D; aim for ~75–125 nmol/L (30–50 ng/mL).
• Typical supplementation: 1000–2000 IU/day vitamin D₃; higher (4000 IU/day) for deficient adults.
• Co-supplement vitamin K₂ if relying on high-dose D, particularly with calcium.

Safety

Toxicity is rare at typical doses; hypercalcaemia from very high doses (>50,000 IU/day chronic) is well-documented.

Related entries

DO-HEALTH, VITAL, Osteoporosis.