This paper shows that prolonged fasting is not a single “healthy” or “harmful” phenomenon, but a powerful biological stressor that can trigger major systemic remodeling while producing very different clinical effects depending on duration, population, and context. It is worth reading because it maps where fasting may improve metabolism and perioperative care, where it may carry real risk, and how a broad, mixed literature can be turned into a clinically usable evidence landscape.
Abstract: The aim of this paper is to systematically review and synthesize the current understanding of the physiological, metabolic, and clinical effects of prolonged fasting, as evidenced by recent research, to identify key themes and delineate areas for future investigation. The review utilises 1402 original studies with 378628 total participants (topic deduplicated ΣN). Across the mapped evidence, prolonged fasting consistently aligns with large-scale systemic remodeling, exemplified by proteomic shifts in over 1,000 proteins after a 7-day water-only fast and marked plasma lipidome changes after 36 hours. Clinical signals are mixed and context-dependent: some studies suggest improved hepatic insulin action and glucose handling with extended fasts, while observational data link longer nightly fasting to both potentially favorable glycemic profiles in women and poorer functional or biomarker profiles in older adults. In vulnerable states, the evidence highlights safety concerns, including an association between ≥13 hours without food during pregnancy and elevated maternal corticotropin-releasing hormone with increased preterm-delivery risk. Practical perioperative evidence indicates that reducing unnecessary fasting is feasible, with protocols such as “apple juice on arrival” shortening clear-fluid fasting from 9.9 to 3.5 hours. Future research should focus on harmonized fasting definitions and longitudinal, stratified human studies that connect molecular adaptations to durable clinical outcomes while explicitly characterizing risk in high-susceptibility groups.
Final search date and database lock: 2026-03-21 01:09:00 CET
Plan: Pro (expanded craft tokens; source: PubMed)
Source: PubMed
Total Abstracts/Papers: 4039
Downloaded Abstracts/Papers: 4039
Included original and non-original Abstracts/Papers (all): 1513
Included original Abstracts/Papers (Vote counting by direction of effect): 1402
Reference Index (links used in paper): 95
Total participants (topic deduplicated ΣN): 378628
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