Impact of Vitamin D Status and Supplementation on Brain-Derived Neurotrophic Factor and Mood-Cognitive Outcomes: A...

Vitamin D deficiency is prevalent in higher-latitude regions and among older adults, and has been linked to depressive symptoms and cognitive decline, although the neurobiological link remains unclear. Brain-derived neurotrophic factor (BDNF) may be a key modulator and mediator of vitamin D-related neuroprotection.

Selected databases (2009-2025) were searched for specific studies reporting vitamin D exposure, BDNF, and mood or cognitive outcomes. Risk of bias was appraised with RoB 2, Newcastle-Ottawa Scale or SYRCLE.

Thirteen studies were included. High-dose vitamin D improves mood primarily when levels are low. Supplementation of at least 2000 IU/day for 12 weeks reduced BDI scores by 1.7-7.6 points and increased BDNF levels by ~7%. Each 1 ng/mL increase in 25(OH)D levels decreased the likelihood of depressive symptoms, especially when BDNF levels were high. In animal studies vitamin D increases hippocampal BDNF and reverses stress-induced depressive behavioral deficits. Adequate vitamin D intake is associated with improved cognitive performance and a dose-dependent increase in BDNF. Each 10 ng/mL increase in 25(OH)D was associated with a 0.6-point increase in MMSE scores and a 15% increase in serum BDNF. Low vitamin D status in children may predict cognitive decline. Animal studies have shown that supplementation with 500-10,000 IU/kg for at least 3 weeks increased hippocampal BDNF and improved biochemical markers of aging.

Vitamin D supplementation may support mood and cognition via BDNF modulation, especially in people with insufficient vitamin D levels (<30 ng/mL), but long-term, adequately powered studies with objective tools are required.