25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype

Abstract

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.

Figure 1.

Mean, SD, and individual values for the half-lives of 25(OH)D₂ (▴) and 25(OH)D₃ (●) for countries combined [18 Gambian (solid symbols) and 18 UK (open symbols) participants] (A) and the countries separated (B). Differences between the half-lives of 25(OH)D₂ and 25(OH)D₃ and country differences are displayed as P values.

Figure 2.

Country-specific relationships between the half-lives and total 25(OH)D, DBP, and b25(OH)D concentrations for 25(OH)D₂ (▴, Gambia; ▵, UK) and 25(OH)D₃ (●, Gambia; ○, UK) in 18 Gambian and 18 UK participants, and Gc-b25(OH)D in 16 Gambian and 12 UK participants. The charts show individual values and country-specific regression lines. Regression line statistics are shown in Table 2.