Prolonged Fasting: Scoping Review with ☸SAIMSARA

To synthesize the original-study evidence on prolonged fasting, emphasizing recurrent biological mechanisms, clinical outcomes, safety signals, implementation issues, and research directions relevant to human health and translational physiology. The review uses 335 references and builds its evidence map from 1406 original studies with 378780 total participants/sample observations (topic-deduplicated ΣN). Across the mapped evidence, prolonged fasting emerges as a potent, context-dependent metabolic stressor rather than a uniformly beneficial or harmful intervention, with its clinical meaning shaped by indication, duration, supervision, and host vulnerability. Recurrent signals indicate a coordinated shift toward lipid oxidation, ketogenesis, and gluconeogenesis—illustrated by systemic proteomic remodeling of more than 1,000 proteins after a 7-day water-only fast and gluconeogenesis supplying roughly 90% of glucose production after 40 hours—alongside consistent harms from unnecessary perioperative fasting and decompensation risk in diabetes, pregnancy, and inherited metabolic disease. This duality suggests that supervised, phenotype-matched fasting protocols, rather than blanket prescriptions or prolonged perioperative nil-by-mouth practices, best reflect current evidence. Future research should prioritize standardized fasting phenotypes paired with risk-stratified safety monitoring to clarify who benefits, who is harmed, and under what refeeding conditions.