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

TL;DR

Vitamin D supplementation significantly reduces depressive symptoms, with higher doses up to 5,000 IU/day showing the most benefit.

Contribution

A dose–response meta-analysis revealing that higher vitamin D doses are more effective in reducing depression symptoms.

Findings

Vitamin D supplementation significantly improved depressive symptoms compared to placebo.

Higher doses of vitamin D (up to 5,000 IU/day) were associated with greater symptom improvement.

Supplementation reduced serum PTH and TNFα levels, indicating anti-inflammatory effects.

Abstract

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

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

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.

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.

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.

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