Peer-reviewed article
Vitamin D neuroimmune synaptic plasticity and precision intervention in pediatric neurodevelopmental disorders.
Xie C, Xiang P, Ye X, Zhang W, Qian Y et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This review examines how vitamin D deficiency affects child brain development through effects on immune response and brain cell connections. Vitamin D deficiency is linked to autism, epilepsy, and ADHD in children, with the most important effects occurring during pregnancy and early childhood. The document proposes that vitamin D supplementation should be personalized based on a child's developmental stage, genetic factors, and biomarkers rather than using the same dose for all children. Current clinical trials show mixed results, suggesting that better-targeted approaches are needed.
Key points
- Vitamin D deficiency is highly prevalent in children worldwide and affects brain development, not just bone health
- Deficiency is significantly associated with autism spectrum disorder, epilepsy, and ADHD
- The critical developmental windows for vitamin D effects are from gestation through preschool period
- Clinical benefits of vitamin D supplementation are heterogeneous, with variation based on dosage, timing, genetic factors (VDR genotype), and other nutrients
- A precision medicine approach is needed, tailoring supplementation to individual developmental stage, biomarkers, and genetic factors
Limitations
This is a review article that synthesizes existing evidence rather than presenting new empirical data. It does not provide a quantitative meta-analysis of intervention outcomes or report on a specific study population, so the strength of evidence for particular supplementation strategies cannot be fully assessed.
Abstract
Vitamin D deficiency is highly prevalent in children worldwide but has long been regarded only as a risk factor for bone health. Emerging evidence indicates that vitamin D profoundly influences child brain development by regulating neuroimmune responses and synaptic plasticity, forming a "neuroimmune-synaptic plasticity axis." Deficiency is significantly associated with the risk of multiple pediatric neurological disorders, including autism spectrum disorder (ASD), epilepsy, and attention-deficit / hyperactivity disorder (ADHD). This axis exerts irreversible regulatory effects during critical developmental windows from gestation to the preschool period, representing a core causal pathway linking vitamin D deficiency to neurodevelopmental disorders. However, the clinical benefits of vitamin D supplementation are highly heterogeneous, necessitating a move beyond the "one-size-fits-all" paradigm. This review systematically integrates causal mechanisms, molecular pathways, disease-specific associations, and clinical evidence, proposing the "neuroimmune-synaptic plasticity axis" as a central hypothesis. We critically analyze the mechanisms of vitamin D during key neurodevelopmental periods and evaluate sources of heterogeneity in existing clinical trials, including dosage, timing, VDR genotype, and co-nutrients. Finally, we propose a research roadmap for individualized supplementation strategies based on developmental stage, biomarkers, and VDR genotype, aiming to transition vitamin D use from empirical to precision intervention.