Hypovitaminosis D and Depression: A Systematic Review of Randomized Controlled Trials

Introduction. Unipolar depression affects millions worldwide, with increasing prevalence and high healthcare costs. As traditional treatments, such as selective serotonin reuptake inhibitors, show variable efficacy, exploring additional factors such as hypovitaminosis D becomes essential. This review examines the effects of vitamin D supplementation on depressive symptoms in randomized controlled trials. Methods. A systematic review of randomized controlled trials published between 2014 and 2024 was conducted using PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials. Eligible studies were randomized controlled trials in human participants, with vitamin D as the primary intervention and depressive symptoms assessed using validated instruments. Eleven studies involving 1,693 participants were included. Results were synthesized narratively. Risk of bias was assessed using the Cochrane Risk of Bias tool. Results. The included trials yielded mixed findings, with some demonstrating improvements in depressive symptoms following vitamin D supplementation and others reporting no significant effect. Increases in serum 25(OH)D levels were consistently observed across intervention groups; however, associated changes in depressive outcomes varied across populations and study designs. Not all trials demonstrated significant benefit, and effects were sometimes limited to specific subgroups. Limitations included performance bias in certain studies due to a lack of blinding, variability in baseline vitamin D status, sample size constraints, and heterogeneity in outcome measures and intervention protocols. No severe adverse effects attributable to vitamin D supplementation were reported, though mild adverse events were noted in a small number of studies. Conclusions. Vitamin D supplementation may be associated with improvements in depressive symptoms in some populations; however, findings remain heterogeneous. Variability in study design, dosing strategies, and population characteristics limits the ability to draw definitive conclusions. Further large-scale, standardized trials are needed to clarify the role of dose, duration, route of administration, and baseline vitamin D status in depressive outcomes.

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Authors

Randall Ordovich-Clarkson; Daniel Lara; Sera Trapani

Published

Jun 7, 2026

Journal or venue

Galician Medical Journal

DOI

10.21802/e-gmj2026-a12

Paper type

journal article

Source

Crossref