Association Between Low Vitamin D Levels and Depression: A Systematic Review and Meta-Analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis primarily comprising longitudinal cohort studies (14 cohorts, 1 RCT)
PubMed 42338858 · doi:10.7759/cureus.109430
What was done
Four databases were searched through December 2024 for longitudinal cohort studies and multivariable-adjusted randomized controlled trials (RCTs) assessing baseline serum 25-hydroxyvitamin D [25(OH)D] and subsequent depression risk. Fifteen studies (14 observational cohorts, 1 RCT; N = 49,931) were evaluated for risk of bias using the Newcastle-Ottawa Scale or Cochrane RoB 2 and pooled using DerSimonian-Laird random-effects meta-analysis.
What was found
Deficiency in 25(OH)D was associated with increased odds of subsequent depression (pooled OR 1.45, 95% CI 1.36-1.56, p < 0.001) with zero observed heterogeneity (I² = 0%, p = 0.68). Odds were higher in European cohorts (OR 1.59, 95% CI 1.40-1.82) and in studies using strict deficiency thresholds (<25 or <30 nmol/L: OR 1.66, 95% CI 1.34-2.05). Sensitivity analysis limited to high-quality studies (n = 13) showed an OR of 1.49 (95% CI 1.38-1.60). Egger's test for publication bias was borderline non-significant (t = 2.02, p = 0.065).
Why it matters
By restricting inclusion to longitudinal cohorts and multivariable-adjusted designs, this meta-analysis minimizes reverse-causation bias and demonstrates a consistent prospective link between vitamin D deficiency and depression risk.
Limits
Fourteen of the 15 included studies were observational cohorts, so residual confounding cannot be ruled out and causality cannot be established. Only one RCT met inclusion criteria. Egger's test showed borderline potential for publication bias (p = 0.065), and the data do not prove whether vitamin D supplementation treats or prevents depression.
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