A major new review published in Biomolecules and Biomedicine reveals that adults with lower vitamin D levels are more likely to experience depression, especially when 25-hydroxy-vitamin D [25(OH)D] falls at or below 30 nmol/L. However, the study emphasizes that this correlation does not establish that vitamin D deficiency directly causes depression.
Depression currently affects approximately 5% of adults worldwide and is projected to become the leading cause of disease burden by 2030. While standard antidepressants offer relief for many, their effects are generally “small to moderate,” increasing interest in modifiable factors such as vitamin D.
Biologically, the connection is plausible. Vitamin D receptors are concentrated in mood-relevant brain regions, including the hypothalamus and pons. Its active form, 1,25-dihydroxy-vitamin D, supports healthy brain signaling, reduces neuro-inflammation, mitigates oxidative stress, and regulates intracellular calcium—pathways long linked to depression.
The review analyzed 66 observational studies from 31 countries, selected from over 8,000 records across PubMed, Scopus, and Web of Science up to April 30, 2023. Due to differences in vitamin D assays and depression measurement tools, the researchers performed a narrative synthesis instead of a meta-analysis. Study quality was assessed using MMAT and MINORS tools, following PRISMA-2020 guidelines, and the review was registered in PROSPERO (CRD42024515918).
Key findings include:
- In 46 cross-sectional studies, lower 25(OH)D levels consistently correlated with higher depressive symptom scores or a depression diagnosis, with the threshold of ≤30 nmol/L aligning most closely with increased depression risk.
- Case-control studies found that individuals with current or remitted major depressive disorder were more likely to have insufficient or deficient vitamin D than healthy controls, often correlating with symptom severity. Some analyses suggested sex-specific effects, mainly in women.
- Among 10 prospective cohort studies, results varied. Certain community and older adult cohorts showed that baseline vitamin D deficiency increased the risk of future depressive symptoms, while other large datasets, including biobank studies, did not find a significant association.
Methodological differences remain a major challenge. Variations in depression instruments, vitamin D assays, and incomplete adjustment for confounding factors—such as sun exposure, BMI, or comorbidities—limit definitive conclusions. Reverse causality is also possible: depression may reduce outdoor activity, lowering vitamin D levels rather than vitamin D deficiency causing depression.
To advance understanding, the authors call for:
- Large longitudinal cohorts with repeated vitamin D measurements
- Objective sunlight exposure data
- Genetic data related to vitamin D metabolism
- Randomized prevention trials in vitamin-D-deficient adults without depression
“Our takeaway is cautious but practical: check vitamin D in adults with depression and correct clear deficiency for overall health—while we run rigorous studies to test whether restoring vitamin D can actually prevent depression,” said Vlad Dionisie, Ph.D., Assistant Professor at Carol Davila University of Medicine and Pharmacy.
The findings reinforce the importance of monitoring vitamin D levels in mental health care while further research clarifies causality.
