Uncovering hidden vitamin D deficiency in overweight children

Table 1 Mechanisms of functional vitamin D deficiency in pediatric obesity

Mechanism (Ref.)	Description	Clinical implications
Adipose sequestration[1,2,6-9]	Vitamin D accumulates in adipose tissue, reducing its availability in circulation	Standard supplementation may be inadequate; requires higher doses for efficacy
Expanded volume of distribution[2,6]	Larger fat mass dilutes serum vitamin D levels	Dose adjustments based on body size or surface area may be necessary
Impaired hepatic 25-hydroxylation[9,10]	Obesity and non-alcoholic liver disease reduce conversion of vitamin D to 25(OH)D	Liver dysfunction must be considered when interpreting low 25(OH)D levels; supplementation may need to be higher or targeted
Inflammation-induced enzyme inhibition[10]	Cytokines downregulate CYP2R1 and related enzymes	Chronic inflammation may impair conversion; treating underlying inflammation may improve vitamin D status
Altered vitamin D-binding protein[11,12]	Obesity may affect DBP levels or affinity, reducing free vitamin D	Standard total 25(OH)D assays may underestimate deficiency; measurement of free or bioavailable vitamin D should be considered
Reduced vitamin D receptor expression/function[13-15]	Obesity-related inflammation may downregulate receptors or impair downstream signaling	May explain symptoms despite adequate serum levels; supports use of functional endpoints in assessing sufficiency
Epigenetic and intracellular alterations[16,17,19]	Obesity may induce VDR resistance via epigenetic and intracellular signaling changes	Emerging concept; may require future biomarker development to detect tissue-level deficiency or resistance

25(OH)D: 25-hydroxyvitamin D; DBP: Vitamin D-binding protein; CYP2R1: Cytochrome P450 2R1; VDR: Vitamin D receptor.