Background: Vitamin D has been increasingly investigated as a potential adjunctive therapy for depressive symptoms, but results remain inconsistent. This study aimed to provide an updated systematic review and meta-analysis of randomized controlled trials (RCTs) published between 2020-2025 to clarify its efficacy and identify potential moderators.
Methods: We conducted a comprehensive search of six electronic databases (PubMed, ProQuest, Wiley, EBSCOhost, Taylor & Francis, and Sage Journals), supplemented by Google Scholar and citation checking, up to August 11, 2025. Eligible studies included RCTs evaluating vitamin D supplementation (any form, dose, or route) against placebo or control in participants with major depressive disorder (MDD) or depressive symptoms assessed via validated scales. A random-effects meta-analysis was done with subgroup analyses examining supplementation dose, intervention duration, baseline vitamin D status and diagnostic methods. Risk of bias was evaluated with RoB 2, and certainty of evidence was assessed with GRADE. This meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and is registered to PROSPERO (CRD420251125689).
Results: Twenty-four RCTs (n = 30,282) were included. Vitamin D supplementation was associated with reduced depressive symptoms (SMD = -0.37, 95% CI [-0.55, -0.19], p < 0.001). In the prespecified subgroup analysis, benefit was observed in trials lasting ≤12 weeks but not >12 weeks, with no significant subgroup difference. Moderate-dose showed a significant within-subgroup effect, but dose subgroup differences were not significant. No moderating effects were observed for baseline vitamin D status or diagnostic method. Evidence of publication bias was detected.
Conclusion: Vitamin D supplementation may be associated with a modest antidepressant effect, however the certainty of evidence was very low because of substantial heterogeneity, imprecision, and publication bias. High-quality, long-duration RCTs with standardized dosing and stratification by baseline vitamin D status are needed before Vitamin D can be recommended as routine adjunctive therapy.
Type of Study:
Review Article |
Subject:
● Psychosocial Health Received: 2026/02/27 | Accepted: 2026/05/31 | Published: 2026/11/4