{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:02:57Z","timestamp":1789599777214,"version":"build-2803163510"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Intermittent fasting (IF) and Periodic fasting (PF) are biologically plausible non-pharmacological interventions. They trigger core metabolic reprogramming from glucose catabolism to ketogenesis and activate conserved nutrient-sensing networks including AMPK and sirtuins, coupled with mTOR\/IGF-1 axis suppression. Such adaptive regulation enhances cellular repair, antioxidant defense and inflammatory homeostasis, conferring multi-system benefits encompassing metabolic improvement, neuroprotection, anti-tumor activity and healthspan extension. Clinically, time-restricted eating (TRE) and fasting-mimicking diets (FMDs) have demonstrated feasibility and short-term efficacy in pilot clinical studies, although their long-term translational potential and durability of benefits remain unproven. However, current research faces major bottlenecks: over-reliance on homogeneous animal models, insufficient high-quality long-term human trials, unresolved individual response heterogeneity, and the lack of validated non-invasive biomarkers and systematic long-term safety evidence. This mini-review systematically elaborates the core regulatory mechanisms of IF and PF through a hierarchical framework that distinguishes primary drivers from secondary consequences and speculative mechanisms, critically evaluates the evidence base across model systems, analyzes key translational barriers, and proposes a prioritized research agenda. Our objective is to provide a conceptually grounded synthesis that identifies genuine scientific uncertainty, distinguishes established knowledge from speculation, and offers a perspective capable of guiding future investigation toward precise clinical translation.<\/jats:p>","DOI":"10.3389\/fnut.2026.1915344","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T14:23:25Z","timestamp":1789482205000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intermittent and periodic fasting: molecular mechanisms, health benefits and research challenges"],"prefix":"10.3389","volume":"13","author":[{"given":"Ya","family":"Liu","sequence":"first","affiliation":[{"name":"School of Graduate Studies, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Basic Medical and Sciences, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s44361-025-00007-z","article-title":"Intermittent fasting: a comprehensive review of cellular mechanisms, metabolic processes, and organ health","volume":"11","author":"Samkari","year":"2025","journal-title":"J Umm Al Qura Univ Med Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.3390\/foods13131960","article-title":"Intermittent fasting: myths, fakes and truth on this dietary regimen 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