What dose of vitamin D is required to achieve target serum 25-hydroxyvitamin D levels in children?

Student thesis: Doctoral ThesisDoctor of Philosophy


Vitamin D supplementation is an effective intervention in the management of vitamin D deficiency. However, there is no consensus on the optimal dosing strategy in children, and the plethora of products, which vary widely in strength, only adds to the confusion. Beyond data showing a substantial increase in healthcare spending on vitamin D prescriptions in recent years, little is known about vitamin D use in clinical practice. The aim of this thesis was to investigate vitamin D prescribing practices, with the goal of identifying opportunities for optimisation. As few pharmacokinetic (PK) studies have been performed to support current vitamin D dosing recommendations, the PK of vitamin D in children was investigated using the method of population PK modelling.

Analysis of data from The Health Improvement Network showed a 26-fold (10.8 to 276.8 per 100 000 person-years) increase in annual incidence of vitamin D prescribing in children between 2008 and 2016 in the United Kingdom (UK). An increasing trend of prescribing pharmacological doses was observed, including to children for whom UK guidelines recommend prevention doses (0% in 2008 to 53% in 2016). Results from high performance liquid chromatography analysis showed that the vitamin D content in food supplement products ranged from 41.2% to 165.3% of labelled claim. Despite the availability of quality assured medicinal grade products, these lower quality food supplement products have continued to be used to fulfil vitamin D prescriptions, accounting for 39.7% of all vitamin D prescriptions dispensed in primary care in England in 2018.

Using population PK modelling, the PK of vitamin D was explored in a cohort of 83 children with chronic kidney disease. The data were best described using a one-compartment allometric model with a basal concentration parameter reflecting endogenous 25-hydroxyvitamin D production and a proportional error model for residual variability. Model-based simulations support the use of a weight-based vitamin D dosing regimen in this population.

The broad discussion on vitamin D use in this thesis provides compelling evidence for the need to optimise vitamin D supplementation use in children.
Date of Award1 Dec 2021
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorJignesh Patel (Supervisor), Rukshana Shroff (Supervisor) & Greta Rait (Supervisor)

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