Neurobiological and Clinical Effects of Vitamin D in Psychiatric Symptoms: A Meta-Analysis and Systematic Review

Abstract

Beyond its traditional function in maintaining calcium and phosphate homeostasis, vitamin D is now widely understood as a neuroactive steroid with regulatory effects on neural transmission, inflammatory modulation, and synaptic adaptability commonly referred to as neuroplasticity. Insufficient vitamin D status has been linked to disturbances in neuroimmune regulation as well as dysregulation of key neurotransmitter systems including dopaminergic, serotonergic, and glutamatergic pathways. This meta-analysis integrates findings from neurobiological research and clinical trials to examine the impact of vitamin D supplementation on a range of psychiatric manifestations, encompassing depressive symptoms, anxiety, psychotic features, and substance-related psychiatric disturbances. A total of 16 randomized controlled trials published between 2016 and 2025 were included, with data synthesized using a random-effects model and standardized assessment instruments such as the BDI, HAM-D, PHQ-9, BAI, STAI-S, and PANSS. The aggregated results indicate that vitamin D supplementation is associated with a small to moderate reduction in overall psychiatric symptom severity, as reflected by a standardized mean difference of −0.33 with a 95% confidence interval ranging from −0.54 to −0.12 and a statistically significant p value of 0.002. More consistent improvements were observed in mild-to-moderate depressive symptoms (SMD = −0.40; 95% CI −0.68 to −0.13; p = 0.004). Among individuals with substance use disorders, vitamin D significantly lowered depressive symptom scores (MD = −3.60; 95% CI −5.19 to −2.00; p < 0.0001), whereas its effects on anxiety symptoms were not significant (SMD = −0.74; 95% CI −1.71 to 0.23; p = 0.14). In psychotic disorders, vitamin D produced no significant improvements across PANSS domains (p > 0.05). vitamin D appears to modulate excitatory-inhibitory neurotransmission, oxidative stress regulation, inflammatory signaling, and monoaminergic pathways, supporting its role as an adjuvant rather than a primary therapeutic agent. Although beneficial in specific clinical contexts, vitamin D shows limited efficacy in severe psychiatric conditions characterized by longstanding neurocircuit abnormalities. Future large-scale RCTs are needed to determine optimal dosing strategies and clinical subgroups most likely to benefit.

HIGHLIGHTS

This study highlights that vitamin D supplementation is associated with reductions in psychiatric symptoms, especially depressive symptoms. Evidence supports its role as an adjunctive intervention rather than a primary treatment in psychiatric care.

GRAPHICAL ABSTRACT