From Fasting to Caloric Restriction: State of the Art and Clinical Implications
7 affiliations
- 1Dietetics and Clinical Nutrition, Bolzano Health District, 39100 Bolzano, Italy
- 2Department of Biology, University of Naples Federico II, 80126 Naples, Italy
- 3UOSD Clinical Nutrition and Dietetic, Hospital Matera, 75100 Matera, Italy
- 4Dietetics and Clinical Nutrition, Azienda Ospedaliera Universitaria Senese, Policlinico Santa Maria Alle Scotte, 53100 Siena, Italy
- 5S. Camillo-Forlanini Hospital, 00152 Rome, Italy
- 6Centro Specialistico di Dietetica e Nutrizione Clinica Matrik, 40138 Bologna, Italy
- 7IRCCS Synlab SDN, 80143 Naples, Italy
Abstract
Fasting and caloric restriction (CR) are central to current nutritional and metabolic research, although the complexity of physiological responses and their clinical applicability have yet to be fully elucidated. This review provides a state-of-the-art overview of fasting-based and CR-based interventions, including prolonged fasting, alternate-day fasting, semi-fasting, fasting-mimicking diets, and time-restricted feeding, with particular emphasis on their role in metabolic health. Mechanistically, these nutritional strategies modulate ketogenesis, autophagy, mitochondrial function, circadian biology, and nutrient-sensing pathways, including AMPK, mTOR, IGF-1, sirtuins, GCN2, and FGF21, thereby shifting cellular programs from growth and substrate storage toward stress resistance, repair, and metabolic flexibility. Current evidence supports beneficial effects of these nutritional interventions on body weight, adiposity, insulin sensitivity, inflammatory tone, and selected cardiometabolic risk factors. Evidence regarding neuroprotection, cancer prevention, and lifespan extension largely comes from preclinical studies, and the responses in humans are still unclear. This review also highlights the relevance of meal timing, refeeding, protein intake, and interindividual variability in shaping physiological responses and clinical outcomes. Overall, fasting and CR should not be viewed as a rigid protocol but as a personalized nutritional framework whose efficacy and safety depend on timing, duration, and patient context.
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BibTeX
@article{lucchin2026from,
title = {{From Fasting to Caloric Restriction: State of the Art and Clinical Implications}},
author = {Lucio Lucchin and Fabiano Cimmino and Eduardo Penna and Carmela Bagnato and Barbara Paolini and Odette Misa Sonia Hassan and Annalisa Maghetti and Maria Grazia Carbonelli and Ilaria Leone and Marco Salvatore and Marianna Crispino and Giovanna Trinchese and Maria Pina Mollica},
journal = {Nutrients},
year = {2026},
month = nov,
doi = {10.3390/nu18213660},
url = {https://www.mdpi.com/2072-6643/18/21/3660},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From Fasting to Caloric Restriction: State of the Art and Clinical Implications
AU - Lucio Lucchin
AU - Fabiano Cimmino
AU - Eduardo Penna
AU - Carmela Bagnato
AU - Barbara Paolini
AU - Odette Misa Sonia Hassan
AU - Annalisa Maghetti
AU - Maria Grazia Carbonelli
AU - Ilaria Leone
AU - Marco Salvatore
AU - Marianna Crispino
AU - Giovanna Trinchese
AU - Maria Pina Mollica
PY - 2026
DA - 2026/11/04
JO - Nutrients
DO - 10.3390/nu18213660
UR - https://www.mdpi.com/2072-6643/18/21/3660
AB - Fasting and caloric restriction (CR) are central to current nutritional and metabolic research, although the complexity of physiological responses and their clinical applicability have yet to be fully elucidated. This review provides a state-of-the-art overview of fasting-based and CR-based interventions, including prolonged fasting, alternate-day fasting, semi-fasting, fasting-mimicking diets, and time-restricted feeding, with particular emphasis on their role in metabolic health. Mechanistically, these nutritional strategies modulate ketogenesis, autophagy, mitochondrial function, circadian biology, and nutrient-sensing pathways, including AMPK, mTOR, IGF-1, sirtuins, GCN2, and FGF21, thereby shifting cellular programs from growth and substrate storage toward stress resistance, repair, and metabolic flexibility. Current evidence supports beneficial effects of these nutritional interventions on body weight, adiposity, insulin sensitivity, inflammatory tone, and selected cardiometabolic risk factors. Evidence regarding neuroprotection, cancer prevention, and lifespan extension largely comes from preclinical studies, and the responses in humans are still unclear. This review also highlights the relevance of meal timing, refeeding, protein intake, and interindividual variability in shaping physiological responses and clinical outcomes. Overall, fasting and CR should not be viewed as a rigid protocol but as a personalized nutritional framework whose efficacy and safety depend on timing, duration, and patient context.
SN - 2072-6643
ER -