25(OH)D2 Half-Life Is Shorter Than 25(OH)D3 Half-Life and Is Influenced by DBP Concentration and Genotype

• Published in: The journal of clinical endocrinology and metabolism Vol. 99; no. 9; pp. 3373 - 3381
• Main Authors: Jones, K. S, Assar, S, Harnpanich, D, Bouillon, R, Lambrechts, D, Prentice, A, Schoenmakers, I
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.09.2014
• Subjects: 24,25-Dihydroxyvitamin D 3 - blood; 25-Hydroxyvitamin D 2 - blood; 25-Hydroxyvitamin D 2 - pharmacokinetics; Adult; Calcifediol - blood; Calcifediol - pharmacokinetics; Calcium, Dietary - metabolism; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450 Family 27; Deuterium; Endocrine Research; Gambia; Genotype; Humans; Linear Models; Male; Models, Biological; Parathyroid Hormone - genetics; Parathyroid Hormone - metabolism; United Kingdom; Vitamin D-Binding Protein - genetics; Vitamin D-Binding Protein - metabolism; Vitamin D3 24-Hydroxylase - genetics; Vitamin D3 24-Hydroxylase - metabolism; Vitamins - blood; Vitamins - pharmacokinetics; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2014-1714

Context: There is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D). Objective: The objective of the study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status. Participants: Healthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study. Interventions: The intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days. Main Outcome Measures: 25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured. Results: 25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country. Conclusions: 25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.