Abstract
Aim The reference nutrient intake for vitamin D in people aged ≥4 years
is 10 μg/day (400 IU/day) in the UK, but the recommended daily allowance
is 15 μg/day (600 IU/day) for people aged 1-70 years in the US. Here, we
aim to compare the 25-hydroxyvitamin D3 (25(OH)D3) serum concentration
profiles between the two doses. Methods With adult trial data, we
constructed a physiologically based pharmacokinetics (PBPK) model of
serum concentrations of vitamin D3 and 25(OH)D3 using nonlinear mixed
effects (NLME) modelling. We used this model to forecast the mean, 5%
and 95% percentiles for serum 25(OH)D3 concentrations. Results Our
final model uses bodyweight to adjust volume of each compartment and
maximum clearance of 25(OH)D. No other covariate was identified. The
model accurately predicted data from trials of a broad range of dose
regimens. We simulated subjects of the average UK male and female
weights with baseline 25(OH)D < 25 nmol/L. Simulation suggests
circulating 25(OH)D concentrations in >5% of men and women
taking 10 μg/day for a year might fail to reach 50 nmol/L, while those
on 15 μg/day were predicted to attain this threshold. Conclusion The two
doses generate significant difference in serum 25(OH)D3 concentrations.
This needs to be considered for choosing the right dose for the public
health guideline.