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Endocrine Adaptations to Prolonged Fasting: From Physiology, Clinical Uncertainties, Translational Challenges to
Rok Herman1,2, Jure Trsan1,3, Luka Lipar1,3
1Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Nutrients
|December 31, 2025
Summary
Prolonged fasting activates endocrine pathways that may benefit heart health, but more research is needed to confirm these effects and ensure safety in clinical practice.
Area of Science:
- Endocrinology
- Metabolic Health
- Nutritional Science
Background:
- Intermittent fasting (IF) and calorie restriction (CR) share potential health benefits.
- Prolonged fasting (PF) may mimic CR's effects through endocrine adaptations.
- Understanding these endocrine changes is crucial for evaluating PF's health implications.
Purpose of the Study:
- To review preclinical and human data on endocrine adaptations during prolonged fasting.
- To explore the potential healthspan benefits of these adaptations.
- To identify knowledge gaps in the research on prolonged fasting and endocrine function.
Main Methods:
- Structured literature search across relevant scientific databases.
- Data extraction and synthesis focusing on endocrine responses to prolonged fasting.
- Analysis of potential implications for healthspan and cardiometabolic health.
Main Results:
- PF induces a consistent pattern of reduced anabolic signaling and transient activation of stress resilience pathways.
- Evidence is limited by small sample sizes, short follow-up, and methodological inconsistencies.
- Potential risks include hormonal imbalances, lean mass loss, and refeeding issues.
Conclusions:
- PF activates conserved endocrine mechanisms potentially linked to cardiometabolic benefits.
- Clinical translation of these benefits remains speculative due to limited evidence.
- Further research is needed to clarify risks, benefits, and optimal protocols for prolonged fasting.
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