Calcifediol (25-OH-D3)

Calcifediol (25-hydroxyvitamin D3) is a pre-hormone and the primary circulating metabolite of vitamin D3 (cholecalciferol), not a traditional macronutrient or food-based micronutrient. It is the hepatic hydroxylation product of vitamin D3, formed in the liver via CYP2R1 and CYP27A1 enzymes. Molecular weight: 400.64 g/mol. As a supplement, it is available in soft-gel capsule form, commonly dosed at 10–60 mcg (400–2,400 IU equivalent in vitamin D3 activity terms), though calcifediol has approximately 3.2x greater potency per microgram than cholecalciferol in raising serum 25(OH)D levels. Serum target reference range: 30–60 ng/mL (75–150 nmol/L). Bioavailability is significantly superior to cholecalciferol, particularly in individuals with fat malabsorption syndromes (e.g., Crohn's disease, bariatric surgery patients), as calcifediol is more water-soluble and does not require lymphatic chylomicron transport to the same degree. Half-life in circulation: approximately 15–25 days, considerably longer than the parent compound D3 (~24 hours). It contains no macronutrients (zero protein, fat, or carbohydrates in active form), no dietary fiber, and no caloric value. Key bioactive role: serves as the immediate substrate for renal CYP27B1 enzyme conversion to calcitriol (1,25-dihydroxyvitamin D3), the biologically active hormonal form. Cofactors required for optimal metabolism include magnesium (for enzyme activation), vitamin K2 (for downstream calcium utilization), and zinc. No significant mineral or secondary micronutrient content inherent to the compound itself.