{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:37:47Z","timestamp":1793216267517,"version":"4.5.0"},"reference-count":128,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ajman University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Intermittent fasting (IF) is emerging as a heterogeneous neurometabolic intervention with the possibility of changing the course of neurodegenerative diseases. Through the modulation of the gut\u2013brain axis (GBA), cellular bioenergetics (or metabolic) reprogramming, and involvement in preserved stress adaptation pathways, IF influences a range of physiological mechanisms, including mitobiogenesis, autophagy, circadian rhythm alignment, and neuroinflammation. This review critically synthesises current preclinical and early clinical evidence illustrating IF\u2019s capability to supplement synaptic plasticity and integrity, reduce toxic proteins (proteotoxic) burden, and rehabilitate glial and immune homeostasis across models of Alzheimer\u2019s disease, Parkinson\u2019s disease, Huntington\u2019s disease, and amyotrophic lateral sclerosis. The key players behind these effects are bioactive metabolites such as short-chain fatty acids (SCFA) and \u03b2-hydroxybutyrate (BHB), and molecular mediators such as brain-derived neurotrophic factor (BDNF). We feature the therapeutic pertinence of IF-induced changes in gut microbiota composition, immune response, and mitochondrial dynamics, and we discuss emerging approaches for merging IF into precision medicine frameworks. Crucial challenges include individual variability, protocol optimisation, safety in cognitively vulnerable populations, and the need for biomarker-guided, ethically grounded clinical trials. Finally, we propose IF as a scalable and flexible intervention that, when personalised and integrated with other modalities, may reframe neurodegeneration from a model of irreversible decline to one of modifiable resilience.<\/jats:p>","DOI":"10.3390\/nu17142266","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:38:27Z","timestamp":1752140307000},"page":"2266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Intermittent Fasting as a Neuroprotective Strategy: Gut\u2013Brain Axis Modulation and Metabolic Reprogramming in Neurodegenerative Disorders"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7621-7132","authenticated-orcid":false,"given":"Zaw Myo","family":"Hein","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Faqhrul Fahmy","family":"Arbain","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, School of Basic Medical Sciences, Faculty of Medicine, University Sultan Zainal Abidin, Kuala Terengganu 20400, TGG, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5682-0938","authenticated-orcid":false,"given":"Suresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Allied Health Science, Faculty of Health and Life Sciences, Management and Science University, Shah Alam 40100, SEL, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9740-6458","authenticated-orcid":false,"given":"Muhammad Zulfadli","family":"Mehat","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, SEL, Malaysia"},{"name":"Brain and Mental Health Research Advancement and Innovation Networks (PUTRA BRAIN), Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, SEL, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5333-4694","authenticated-orcid":false,"given":"Hafizah Abdul","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, SEL, Malaysia"},{"name":"Brain and Mental Health Research Advancement and Innovation Networks (PUTRA BRAIN), Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, SEL, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5261-0391","authenticated-orcid":false,"given":"Muhammad Danial","family":"Che Ramli","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Allied Health Science, Faculty of Health and Life Sciences, Management and Science University, Shah Alam 40100, SEL, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-4565","authenticated-orcid":false,"given":"Che Mohd Nasril","family":"Che Mohd Nassir","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, School of Basic Medical Sciences, Faculty of Medicine, University Sultan Zainal Abidin, Kuala Terengganu 20400, TGG, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Gonz\u00e1lez, N., Gon\u00e7alves-S\u00e1nchez, J., G\u00f3mez-Nieto, R., Gon\u00e7alves-Estella, J.M., and L\u00f3pez, D.E. 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