Effects of vitamin D supplementation on depression and some selected pro-inflammatory biomarkers: a double-blind randomized clinical trial

Double-blind randomized clinical trial conducted in adults with mild to moderate depression recruited from outpatient clinics of Baharloo Hospital in Tehran, Iran. The active vitamin D arm included 28 participants; participants with other psychiatric diseases were excluded, and prior vitamin D supplement use was not allowed.

Oral vitamin D3 (cholecalciferol) was given at 50,000 IU every 2 weeks for 8 weeks. The trial compared this regimen with placebo in a double-blind randomized design.

Vitamin D3 supplementation improved depressive symptoms and raised circulating 25(OH)D, but it did not meaningfully change the selected inflammatory biomarkers. In the intervention arm, 25(OH)D increased by 40.83 ± 28.57 nmol/L versus 5.14 ± 23.44 nmol/L in control (P < 0.001), and BDI-II scores decreased by 11.75 ± 6.40 versus 3.61 ± 10.40 in control (P = 0.003). IL-1β, IL-6, and hs-CRP showed no significant within- or between-group differences. Final iPTH did not differ significantly between groups, although the control group showed a within-group increase of 5.10 ± 6.002 pg/mL (P < 0.001).

The active intervention arm was small, and the treatment period was short at 8 weeks. The study population was limited to adults with mild to moderate depression from a single center in Tehran, which may reduce generalizability. Inflammatory biomarkers did not change, so the mechanism for symptom improvement remains uncertain.