EVALUATING THE IMPACT OF VITAMIN D SUPPLEMENTATION ON ANXIETY AND DEPRESSION: A SYSTEMATIC REVIEW OF RCTS

Abstract

Background: Vitamin D deficiency has been associated with mood disorders including anxiety and depression. Mechanistic pathways involve inflammation, neurotransmitter regulation, and hypothalamic–pituitary–adrenal (HPA) axis function. Clinical trial evidence has been inconsistent. Objective: To systematically review randomized controlled trials (RCTs) examining the effects of Vitamin D supplementation on depression and anxiety outcomes. Methods: A systematic search was conducted across PubMed, Embase, Scopus, Cochrane Library, and PsycINFO up to September 2023. Eligible studies included RCTs of Vitamin D supplementation versus placebo/standard care in adults, reporting outcomes on depression or anxiety using validated scales. Risk of bias was assessed with the Cochrane RoB 2 tool. Data were synthesized qualitatively and supplemented with quantitative results from recent meta-analyses. Results: Forty-one RCTs (53,235 participants) demonstrated a small-to-moderate reduction in depressive symptoms with Vitamin D versus control (Hedges’ g = −0.317; 95% CI: −0.405 to −0.230, p < 0.001). Subgroup analyses revealed greater benefit in patients with low baseline 25(OH)D levels (<50 nmol/L) and with supplementation ≥2,800 IU/day for ≥8 weeks. Evidence for anxiety was limited: a dose–response meta-analysis of seven RCTs (n ≈ 641) found no significant effect, whereas pooled analyses of “negative emotions” across 25 RCTs (7,534 participants) suggested moderate benefit (Hedges’ g = −0.499; 95% CI −0.845 to −0.153; I²=97.7%). One RCT reported improved anxiety in Vitamin-D-deficient depressed patients after six months, but not depression. Conclusion: Vitamin D supplementation appears to modestly improve depressive symptoms, particularly in deficient populations, with higher doses and longer treatment. Evidence for anxiety remains inconclusive. Further large-scale, deficiency-targeted RCTs with anxiety as a primary outcome are needed.