Vitamin D regulation of cortisol through the HPA axis: A focused review

Vitamin D has a significant influence on neuroendocrine regulation by modulating cortisol levels through hypothalamic-pituitary-adrenal (HPA) axis mechanisms. This review explores the biological mechanisms connecting vitamin D to cortisol regulation and its clinical implications beyond bone health. Vitamin D receptors are widely distributed in stress-responsive brain regions, and evidence suggests that vitamin D signaling regulates cortisol through both genomic and non-genomic pathways. Clinical findings are mixed; some studies suggest cortisol levels decrease after vitamin D supplementation in cases of obesity, depression, or inflammation, while others show minimal effects in healthy populations. This relationship varies with age and gender. Variability in study results stems from differences in research design, baseline vitamin D levels, cortisol measurement methods, and genetic polymorphisms that affect metabolism. Despite this, vitamin D acts as a modulator of the stress response, especially benefiting vulnerable groups. Future research should implement standardized protocols that consider circadian rhythms and population differences. • Vitamin D receptors in brain regions control stress hormone cortisol production. • Vitamin D modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis. • The effects of vitamin D levels on cortisol patterns vary according to age and gender. • Genomic and non-genomic pathways mediate vitamin D influence on HPA axis function.