Time-Restricted Feeding as a Circadian Therapeutic Strategy for Alzheimer’s Disease
DOI:
https://doi.org/10.61173/1fs4g940Keywords:
Time-restricted feeding, Circadian rhythm, Alzheimer’s disease, NeurodegenerationAbstract
Time-Restricted Feeding (TRF), a form of intermittent fasting, has been recognized as a promising nonpharmacological intervention for improving circadian rhythms and metabolic health. Given the critical role of circadian rhythm disruption in Alzheimer’s disease (AD) pathogenesis, TRF is gaining increasing attention as a potential strategy for mitigating AD pathology. This review examines the biological mechanisms through which TRF influences AD-related processes, including circadian rhythms, amyloid-β deposition, tau pathology, and neuroinflammation. Animal studies demonstrate that TRF enhances neuronal resistance, improves synaptic plasticity, and modulates AD-associated metabolic pathways. Concurrently, clinical research suggests TRF may improve sleep architecture and cognitive function, though challenges remain regarding adherence and long-term efficacy. By integrating animal and human studies, this review highlights TRF’s multiple roles in AD prevention and treatment. Notably, TRF serves not only as a circadian rhythm-based lifestyle intervention but also as a potential significant adjunct strategy in AD therapy. Future directions include conducting long-term clinical trials and developing personalized treatment plans based on individual genotypes and chronotypes to maximize therapeutic benefits.
References
[1] GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the global burden of disease study 2019. The Lancet Public Health, 2022, 7(2). https://doi. org/10.1016/s2468-2667(21)00249-8
[2] Scheltens Philip. Alzheimer’s disease. The Lancet, 2021, 397(10284): 1577–1590. https://doi.org/10.1016/S0140- 6736(20)32205-4
[3] Irwin Michael Robert, Vitiello Michael Vincent. Implications of sleep disturbance and inflammation for Alzheimer’s disease dementia. The Lancet Neurology, 2019, 18(3): 296–306. https:// doi.org/10.1016/s1474-4422(18)30450-2
[4] Dallmann Roland, Brown Steven Alan, Gachon Fabrice. Chronopharmacology: New insights and therapeutic Dean&Francis Zhiyou Fan implications. Annual Review of Pharmacology and Toxicology, 2014, 54(1): 339–361. https://doi.org/10.1146/annurevpharmtox-011613-135923
[5] Whittaker David Samuel, Akhmetova Lilia, Carlin Daniel, Romero Hector, Welsh David Kenneth, Colwell Christopher Samuel, Desplats Paula. Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease. Cell Metabolism, 2023, 35(10). https://doi.org/10.1016/j.cmet.2023.07.014
[6] Xie Yaping, Tang Qiang, Chen Guoliang, Xie Min, Yu Shuhua, Zhao Jian, Chen Li. New insights into the circadian rhythm and its related diseases. Frontiers in Physiology, 2019, 10: 682. https://doi.org/10.3389/fphys.2019.00682
[7] Currenti Walter, Godos Justyna, Castellano Stefania, Caruso Giuseppe, Ferri Rosaria, Caraci Filippo, Grosso Giuseppe, Galvano Francesca. Association between time restricted feeding and cognitive status in older Italian adults. Nutrients, 2021, 13(1): 191. https://doi.org/10.3390/nu13010191
[8] Tinsley Grant Michael, La Bounty Paul Michael. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutrition Reviews, 2015, 73(10): 661–674. https://doi.org/10.1093/nutrit/nuv041
[9] Currenti Walter, Godos Justyna, Castellano Stefania, Mogavero Maria Pina, Ferri Rosaria, Caraci Filippo, Grosso Giuseppe, Galvano Francesca. Time restricted feeding and mental health: A review of possible mechanisms on affective and cognitive disorders. International Journal of Food Sciences and Nutrition, 2020, 72(6): 723–733. https://doi.org/10.1080/096374 86.2020.1866504
[10] Pan Xia, Taylor Michael James, Cohen Emily, Hanna Nasser, Mota Samuel. Circadian clock, time-restricted feeding and reproduction. International Journal of Molecular Sciences, 2020, 21(3): 831. https://doi.org/10.3390/ijms21030831
[11] Shimazu Takashi, Hirschey Matthew David, Newman John, He Wei, Shirakawa Katsuhiko, Le Moan Nicolas, Grueter Caroline Ann, Lim Hyunsuk, Saunders Laura Rose, Stevens Richard David, Newgard Christopher Bruce, Farese Robert Vincent, de Cabo Rafael, Ulrich Sabine, Akassoglou Koros, Verdin Eric. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science, 2012, 339(6116): 211–214. https://doi.org/10.1126/ science.1227166
[12] Onyango Isaac Godfrey, Jauregui Gabriel Victor, Čarná Markéta, Bennett Jeffrey Patrick, Stokin Gary Brian. Neuroinflammation in Alzheimer’s disease. Biomedicines, 2021, 9(5): 524. https://doi.org/10.3390/biomedicines9050524
[13] Rangan Priscilla, Lobo Fabio, Parrella Enrico, Rochette Nicolas, Morselli Luca, Stephen Thomas Laurence, Cremonini Alessandra Lucia, Tagliafico Luca, Persia Antonella, Caffa Ilaria, Monacelli Francesco, Odetti Pierluigi, Bonfiglio Tiziana, Nencioni Andrea, Pigliautile Michele, Boccardi Valentina, Mecocci Patrizia, Pike Christian John, Cohen Philip, LaDu Mary Jane. Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer’s models. Cell Reports, 2022, 40(13): 111417. https://doi.org/10.1016/ j.celrep.2022.111417
[14] Hein Zaw Min, Arbain Mohd Fadhil Farid, Kumar Suresh, Mehat Mohd Zulkefli, Hamid Haslina Amin, Che Ramli Mohd Dzulfadzli, Che Mohd Nassir Che Mohd Noor. Intermittent fasting as a neuroprotective strategy: Gut–Brain axis modulation and metabolic reprogramming in neurodegenerative disorders. Nutrients, 2025, 17(14): 2266. https://doi.org/10.3390/ nu17142266
[15] Anton Stephen Daniel, Lee Seok Ahn, Donahoo William Thomas, McLaren Christopher, Manini Todd, Leeuwenburgh Christiaan, Pahor Marco. The effects of time restricted feeding on overweight, older adults: a pilot study. Nutrients, 2019, 11(7): 1500. https://doi.org/10.3390/nu11071500
[16] Ezzati Armin, Tamargo Juan Antonio, Golberg Laura, Haub Michael David, Anton Stephen Daniel. The effects of time-restricted eating on inflammation and oxidative stress in overweight older adults: a pilot study. Nutrients, 2025, 17(2): 322–322. https://doi.org/10.3390/nu17020322
[17] Gasmi Maha, Hardiany Novi Silvia, Marie Martins Ivo Jose, Sharma Anu, Williams-Hooker Rebecca. The influence of time-restricted eating/feeding on Alzheimer’s biomarkers and gut microbiota. Nutritional Neuroscience, 2024, 1–15. https:// doi.org/10.1080/1028415x.2024.2359868
Downloads
Published
Issue
Section
License
Copyright (c) 2025 by the authors.

This work is licensed under a Creative Commons Attribution 4.0 International License.
