Vitamin D supplementation and incidence of major depressive disorder - A randomized clinical trial

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#humans #major-depressive-disorder #female #male #dietary-supplements

Vitamin D supplementation and incidence of major depressive disorder - A randomized clinical trial

Ahl et al., 2026 | Clin Nutr | Rct

Citation

Ahl Noora-Maria, Hantunen Sari, ... Virtanen Jyrki K. Vitamin D supplementation and incidence of major depressive disorder - A randomized clinical trial. Clin Nutr. 2026-Feb;57:106570. doi:10.1016/j.clnu.2025.106570

Abstract

BACKGROUND AND AIMS: Depression is a significant public health issue, but current prevention methods are limited. Vitamin D has shown some promise in treatment of depression, but evidence for primary prevention is inconclusive. We investigated the effects of long-term vitamin D3 supplementation on the incidence of major depressive disorder (MDD). METHODS: The study was a randomized placebo-controlled clinical trial conducted in 2012-2018. Participants were randomized to receive either 1600 IU/day (n = 814) or 3200 IU/day (n = 817) of vitamin D3 or placebo (n = 803) for 5 years. The primary endpoint of the current study was incident MDD, diagnosed by physician, during the 5-year supplementation period. The secondary endpoint was incident MDD during an extended follow-up until the end of 2021. A sub-cohort of 542 participants had more detailed in-person investigations. RESULTS: Among 2434 participants (mean age 68.2 years; 42.5 % women), 1786 completed the 5-year intervention. During the mean 4.2-year follow-up, there were 14, 11 and 8 MDD events in the placebo, 1600 IU/day (hazard ratio (HR), 0.78; 95 % CI 0.35-1.71; P = 0.53), and 3200 IU/day (HR, 0.57; 95 % CI 0.24-1.35; P = 0.20) arms. During the extended mean 7.8-year follow-up, there were in total 29, 18 and 16 MDD events in the placebo, 1600 IU/day (HR, 0.61; 95 % CI 0.34-1.10; P = 0.10) and 3200 IU/day (HR 0.54; 95 % CI 0.30-1.00; P = 0.05) arms. In the sub-cohort, the mean ± SD baseline serum 25-hydroxyvitamin D concentration was 75 ± 18 nmol/L. After 12 months, the concentrations were 73 ± 18 nmol/L, 100 ± 21 nmol/L, and 120 ± 22 nmol/L in the placebo, 1600 IU/day, and 3200 IU/day arms, respectively. CONCLUSIONS: Vitamin D3 supplementation did not lower the incidence of MDD during the 5-year supplementation period among largely vitamin D sufficient aging adults. However, there was a borderline indication of benefit during a longer follow-up, possibly suggesting a delayed effect of supplementation. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813 (date of registration Nov 1, 2011).

Key Findings

Among 2434 participants (mean age 68.2 years; 42.5 % women), 1786 completed the 5-year intervention. During the mean 4.2-year follow-up, there were 14, 11 and 8 MDD events in the placebo, 1600 IU/day (hazard ratio (HR), 0.78; 95 % CI 0.35-1.71; P = 0.53), and 3200 IU/day (HR, 0.57; 95 % CI 0.24-1.35; P = 0.20) arms. During the extended mean 7.8-year follow-up, there were in total 29, 18 and 16 MDD events in the placebo, 1600 IU/day (HR, 0.61; 95 % CI 0.34-1.10; P = 0.10) and 3200 IU/day (HR 0.54

Outcomes Measured

  • depression

Population

Field Value
Population See abstract
Sample Size 814
Age Range mean age 68.2
Condition depression

MeSH Terms

  • Humans
  • Major Depressive Disorder
  • Female
  • Male
  • Dietary Supplements
  • Aged
  • Incidence
  • Middle Aged
  • Cholecalciferol
  • Vitamin D
  • Vitamins
  • Double-Blind Method

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Randomized Controlled Trial
  • Vertical: vitamin-d-mood

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09