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Efficacy of vitamin D supplementation in patients diagnosed with depression: a dose-response meta-analysis of randomized controlled trials.

  • 2026-03-17
  • Frontiers in nutrition 13
    • Hsuan-Hsien Liu
    • Ting-Hui Liu
    • Chia-Yu Liu
    • Jheng-Yan Wu
    • Chien-Ho Lin
    • Chih-Cheng Lai

Study Design

Type
Systematic Review
Sample size
n = 962
Population
962 participants from 15 studies
Methods
systematic review and meta-analysis of randomized controlled trials using PubMed, EMBASE, and Cochrane Library from inception to June 2024

Background

Depression affects 5% of the global population, posing significant health and economic challenges.

Objectives

This study evaluates the efficacy of vitamin D supplementation in reducing depressive symptoms and explores its dose-response relationship.

Methods

We used PubMed, EMBASE, and Cochrane Library to identify randomized controlled trials using the keyword combination of vitamin D and depression from inception to June 2024. The primary outcome was the change in depressive symptoms. A dose-response meta-analysis using restricted cubic splines was conducted to explore potential sources of heterogeneity and examine the dose-response relationship.

Results

The outcomes were reported in 15 studies encompassing data from 962 participants. Vitamin D supplementation demonstrated a significant improvement in depressive symptoms compared to the placebo group (SMD: -0.98; 95% CI - 1.28 to -0.68; p < 0.001). Statistical heterogeneity was high (I2 = 79%; p < 0.001). Secondary outcomes revealed significant reductions in serum PTH (MD: -4.19; 95% CI - 8.18 to -0.2 pg./mL) and TNFα levels (MD: -0.3; 95% CI - 0.44 to -0.16 pg./mL) in the intervention groups, while other outcomes, such as BMI, weight, and IL-6, showed no significant changes. Dose-response analysis further highlighted that higher daily doses of vitamin D, particularly up to 5,000 IU/day, were associated with the greatest reduction in depressive symptoms.

Conclusion

Our findings from this systematic review and meta-analysis indicated that vitamin D supplementation may be an effective adjunctive therapy for improving depressive symptoms. The observed reductions in serum PTH and TNFα levels suggest anti-inflammatory mechanisms underlying its antidepressant effects. Higher daily doses, particularly around 5,000 IU, were associated with greater symptom improvement within the studied populations.

Research Insights

  • Vitamin D→Improved Depressive Symptoms

    Vitamin D supplementation demonstrated a significant improvement in depressive symptoms compared to the placebo group (SMD: -0.98; 95% CI - 1.28 to -0.68; p < 0.001).

    Effect
    Beneficial
    Effect size
    Large
    Dose
    up to 5,000 IU/day
  • Vitamin D→Reduced Body Mass Index

    while other outcomes, such as BMI, weight, and IL-6, showed no significant changes.

    Effect
    Neutral
    Effect size
    Small
    Dose
    up to 5,000 IU/day
  • Vitamin D→Reduced Body Weight

    while other outcomes, such as BMI, weight, and IL-6, showed no significant changes.

    Effect
    Neutral
    Effect size
    Small
    Dose
    up to 5,000 IU/day
  • Vitamin D→Reduced Interleukin-6 Levels

    while other outcomes, such as BMI, weight, and IL-6, showed no significant changes.

    Effect
    Neutral
    Effect size
    Small
    Dose
    up to 5,000 IU/day
  • Vitamin D→Reduced Parathyroid Hormone Level

    Secondary outcomes revealed significant reductions in serum PTH (MD: -4.19; 95% CI - 8.18 to -0.2 pg./mL)

    Effect
    Beneficial
    Effect size
    Small
    Dose
    up to 5,000 IU/day
  • Vitamin D→Reduced Tumor Necrosis Factor Alpha

    and TNFα levels (MD: -0.3; 95% CI - 0.44 to -0.16 pg./mL) in the intervention groups

    Effect
    Beneficial
    Effect size
    Small
    Dose
    up to 5,000 IU/day
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