Effects of Vitamin D Supplementation on Depression and Some Involved Neurotransmitters

Background: Low vitamin D levels are associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis and depression but a causal relationship has not been established. This study aimed to evaluate the effects of vitamin D supplementation on depression severity, serum 25(OH)D, and some neurotransmitters in patients with mild to moderate depression.

Methods: An 8-week double-blind randomized clinical trial was conducted on 56 subjects with mild to moderate depression, aged 43.0 ± 1.15yrs. The patients were randomly allocated into two groups: intervention (50,000 IU cholecalciferol/2wks) and control (placebo). Biochemical parameters (serum 25(OH)D, iPTH, oxytocin and platelet serotonin), and depression severity (Beck Depression Inventory-II (BDI-II)) were initially and finally assessed.

Results: Following intervention, significant changes were observed in the intervention group compared to the controls: 25(OH)D concentrations increased (+40.83±28.57 vs. +5.14±23.44 nmol/L, P<0.001) and BDI scores decreased (-11.75±6.40 vs. -3.61±10.40, P = 0.003). Oxytocin concentrations were significantly reduced in controls (-6.49±13.69 ng/mL, P = 0.01), but between -group differences were insignificant. Within- and between-group differences of platelet serotonin concentrations were not significant; however, the increment in controls was higher (+0.86±10.82 vs. +0.26±9.38 ng/mL, P = 0.83).

Limitations: Study duration may not reflect the long-term effects of vitamin D on depression. It seems necessary to assess tryptophan-hydroxylasetypes1&2 in relation to vitamin D in serotonin pathways.

Conclusions: Eight-week supplementation with 50,000 IU/2wks vitamin D, elevated 25(OH)D concentration of subjects with mild to moderate depression and significantly improved their depression severity. However, there was no evidence that the anti-depressive effect of vitamin D supplementation is mediated by the measured neurotransmitters.