AUTHOR=Zhou Xiao , Chen Yuhe , Xu Jianxin , Li Xiaobing , Wu Yanmei , Xu Lidan 
  
TITLE=The interplay between childhood obesity and vitamin D deficiency: mechanisms and implications
  
JOURNAL=Frontiers in Pediatrics
  
VOLUME=Volume 13 - 2025
  
YEAR=2026
  
URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2025.1700949
  
DOI=10.3389/fped.2025.1700949
  
ISSN=2296-2360
  
ABSTRACT=Childhood obesity and vitamin D deficiency (VDD) are intertwined global health threats that amplify each other beyond their individual skeletal or metabolic consequences. This review synthesises a decade of clinical, translational and Mendelian-randomisation evidence to show that obesity drives VDD through volume dilution, adipose-tissue sequestration and metabolic associated steatotic liver disease (MASLD)-related hydroxylase dysfunction, while VDD in turn aggravates adipogenesis, leptin resistance and chronic low-grade inflammation, locking children into a self-perpetuating cycle. Meta-analysis of 12 randomised trials (n = 1,538) revealed that vitamin D supplementation improves insulin sensitivity and lowers systolic blood pressure only when baseline 25-hydroxyvitamin D (25(OH)D) is <20 ng/mL and systemic inflammation is modest; no consistent reduction in BMI or fat mass was observed. Obese youths require 2–3 times the standard dose to reach 30 ng/mL, yet incremental metabolic benefit plateaus near 4,000 IU/day and is lost when systemic inflammation is present. Precision-dosing algorithms incorporating VDR/CYP2R1/DBP genotypes and MASLD status are urgently needed. Multi-omic longitudinal trials should clarify the adipose-tissue threshold at which hepatic cytochrome P450 family 27 subfamily B member 1 (CYP27B1) becomes substrate-limited and evaluate the vascular safety of intermittent high-dose boluses before personalised supplementation is translated into routine paediatric practice.