Systematic review of optimizing brain-targeted vitamin D delivery: Novel approaches to enhance mental illness therapeutics

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#vitamin-d #humans #mental-disorders #brain #animals

Systematic review of optimizing brain-targeted vitamin D delivery: Novel approaches to enhance mental illness therapeutics

He et al., 2025 | Brain Res | Systematic Review

Citation

He Jinghu, Gao Zhiyuan, ... Gao Biao. Systematic review of optimizing brain-targeted vitamin D delivery: Novel approaches to enhance mental illness therapeutics. Brain Res. 2025-Jul-01;1858:149656. doi:10.1016/j.brainres.2025.149656

Abstract

BACKGROUND: Vitamin D is increasingly recognized for its neuroprotective, anti-inflammatory, and immunomodulatory roles in mental health. However, its delivery to the central nervous system remains constrained by various factors. OBJECTIVE: This systematic review evaluates strategies for optimizing brain-targeted vitamin D delivery, highlighting molecular, physiological, and technological approaches to enhance its efficacy in mental disorders. METHODS: Following PRISMA guidelines, a comprehensive search across PubMed, Web of Science, Scopus, Embase, and PsycINFO was conducted. Relevant studies were assessed thematically, focusing on BBB transport mechanisms, nanocarriers, structural modifications, and transporter-mediated delivery. RESULTS: Strategies including nanotechnology, biotin-based transporter targeting (e.g., SMVT/SLC5A6), DBP-Megalin/Cubilin-mediated transcytosis, and intranasal administration show promise in enhancing vitamin D brain uptake. Differences between serum and brain vitamin D concentrations, genomic and non-genomic VDR pathways, and psychiatric disorder-specific associations (e.g., depression, schizophrenia, ASD) were also examined. CONCLUSIONS: Although limited by the scarcity of large-scale clinical data, emerging strategies demonstrate significant potential in enhancing brain-targeted vitamin D delivery. These findings lay a foundation for future translational research aimed at precision mental health interventions.

Key Findings

Strategies including nanotechnology, biotin-based transporter targeting (e.g., SMVT/SLC5A6), DBP-Megalin/Cubilin-mediated transcytosis, and intranasal administration show promise in enhancing vitamin D brain uptake. Differences between serum and brain vitamin D concentrations, genomic and non-genomic VDR pathways, and psychiatric disorder-specific associations (e.g., depression, schizophrenia, ASD) were also examined.

Outcomes Measured

  • depression
  • inflammatory markers

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition depression

MeSH Terms

  • Vitamin D
  • Humans
  • Mental Disorders
  • Brain
  • Animals
  • Drug Delivery Systems
  • Blood-Brain Barrier
  • Vitamins

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Systematic Review, Journal Article
  • Vertical: biotin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09