Nutritional timing and stress biology: intermittent fasting as a hormetic signal for adaptation

Abstract

Intermittent fasting (IF) and time-restricted eating (TRE) are recognized as metabolic interventions that link energy balance regulation with influence on stress-related physiological and neuroendocrine processes. Accumulating evidence suggests that IF acts as a mild, controllable stressor that triggers adaptive cellular and systemic responses. Central mechanisms that are involved in these effects are nutrient-sensing pathways, including AMP-activated protein kinase, sirtuins, the target of rapamycin (TOR), and insulin signaling pathways, which collectively coordinate metabolic flexibility and stress adaptation. IF has been shown to modulate hypothalamic–pituitary–adrenal (HPA) axis activity and promote redox and inflammatory homeostasis. This review discusses both preclinical and clinical studies examining the effects of IF and TRE on stress biology and mental health, which frequently report heterogeneous and, in some cases, contradicting effects. Reported effects may vary depending on study design, experimental model, phenotype, and fasting protocol. By integrating data from experimental research, this review highlights the bidirectional interaction between nutritional timing and stress biology and emphasizes that hormesis is a potential mechanism underlying stress resilience. This review also emphasizes the need to carefully balance potential benefits against risks when considering IF interventions for stress resilience and mental health maintenance.