Intermittent fasting: Impact, mechanisms and cautions across medical and lifestyle domains

Intermittent fasting (IF) has emerged as a promising dietary approach with prospective advantages for clinical as well as non-clinical applications. Research indicates that IF enhances insulin sensitivity, facilitates weight reduction and stimulates cellular repair pathways, including autophagy. Physiological adaptations to fasting are reflected in favorable alterations in biomarkers and metabolic processes. This review examines the current evidence on IF by analyzing studies retrieved through schematic searches of the MEDLINE via PubMed database, Embase and ScienceDirect using specific keyword combinations. It focuses on commonly practiced regimens- Time-restricted eating (TRE) (16/8 method), Alternate-day fasting (ADF), the 5:2 intermittent energy-restriction diet and One meal a day (OMAD) approaches and explores their effects on cardiovascular function, metabolic regulation, cognitive performance and longevity. Various IF regimens including the TRE (16/8 method), ADF, the 5:2 diet and OMAD approaches are discussed in relation to their effects on cardiovascular health, cognitive function, metabolic regulation, aging and longevity. While most finding highlight significant health benefits, inconsistencies and methodological limitations are also reported. Mechanistically, IF orchestrates a coordinated metabolic response through modulation of key nutrient sensing pathway such as AMP activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR) and unc-51-like kinase 1 (ULK1). These cascades interact with Sirtuins (SIRT1/3), peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α) and the transcription factor EB (TFEB) to regulate autophagy, mitochondrial biogenesis, oxidative stress defense and cellular repair. Clinically, these molecular events underpin improvements in glycaemic control, lipid metabolism and inflammatory balance, supporting the therapeutic potential of IF for cardiometabolic disorders, neuroprotection and healthy aging.