Recent Updates about the Effects of Vitamin C on the hypothalamic–pituitary–adrenal axis: A review

The HPA axis is a central mediator of the stress response, metabolism balance and immune–neuroendocrine crosstalk. Insight continues to draw attention regarding the control of vitamin C as a crucial cofactor in the regulation at many levels of this axis from neurotransmitter regulation in the hypothalamus to steroid hydroxylation in adrenal gland. This review summarizes current insights in the physiological and molecular interactions by vitamin C with HPA axis, focusing on its involvement in cortisol synthesis, antioxidant system, influencing of ACTH sensitivity and regulating the glucocorticoid-feedback. Special emphasis is placed on advances from experimental, clinical and translational studies which reveal how the availability of vitamin C influences the capacity for stress adaptation, neuroendocrine signalling as well as inflammatory pathways. The review also outlines inconsistencies between studies, methodological considerations and unexamined mechanistic connections that may explain the variation in findings. In summarizing the most recent works, this review presents a comprehensive view of vitamin C–HPA axis crosstalk and its putative clinical relevance in stress-related, metabolic, and inflammatory diseases.