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Vitamin D and Vitamin B12 in Psychiatric Disorders: An Exploratory Systematic Review and Meta-Analysis of Nutrient-Specific Status and Supplementation Evidence.

  • 2026-05-10
  • Diseases (Basel, Switzerland) 14(5)
    • Lavinia-Alexandra Moroianu
    • Cecilia Curis
    • Valeriu Ardeleanu
    • Roxana Elena Bogdan-Goroftei
    • Simona-Dana Mitincu-Caramfil
    • Marius Moroianu
    • Alina Pleșea-Condratovici

Study Design

Type
Review
Population
human studies (N = 69,902)
Methods
PRISMA 2020 systematic review and exploratory meta-analysis; 46 studies (24 RCTs, 22 observational studies); effects harmonized to ORs and pooled using Hartung-Knapp random-effects models

Background/objectives

Evidence linking vitamins D and B12 to psychiatric outcomes remains heterogeneous across designs, populations, phenotypes, exposures, and outcome formats.

Methods

We conducted a PRISMA 2020 systematic review and exploratory meta-analysis of nutrient-specific status and supplementation evidence. PubMed/MEDLINE, APA PsycInfo, Cochrane Library, Google Scholar, ClinicalTrials.gov, and ProQuest were searched for human studies published in 2016-2025, with a final update on 1 March 2026. Forty-six studies were included (24 randomized controlled trials, 22 observational studies; N = 69,902), and 44 contributed quantitative data. Effects were harmonized to odds ratios (ORs) for cross-family comparability and pooled using Hartung-Knapp random-effects models; supplementation evidence was additionally interpreted on the standardized mean difference (SMD) scale.

Results

Across the main evidence families, pooled estimates showed substantial heterogeneity and limited generalizability. Vitamin D supplementation showed an initial inverse estimate on the secondary harmonized OR scale (OR = 0.439, 95% CI 0.272-0.710) and a clinically interpretable SMD of -0.454 (95% CI -0.718 to -0.189), but heterogeneity was high (I2 = 84.2%) and trim-and-fill attenuated the OR estimate to the null (OR = 0.88, 95% CI 0.48-1.63). Vitamin D status showed a similar pattern (primary OR = 0.615, 95% CI 0.424-0.890; trim-and-fill OR = 0.90, 95% CI 0.54-1.49). Vitamin B12 status was inversely associated with outcomes (OR = 0.310, 95% CI 0.115-0.834), but heterogeneity was extreme (I2 = 94.8%). B12 supplementation evidence was sparse and null.

Conclusions

The evidence supports targeted deficiency assessment, not routine supplementation.

Research Insights

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