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

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.