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Updated: Aug 19, 2025

Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice

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Published on: November 27, 2019

Long-term fasting: Multi-system adaptations in humans (GENESIS) study-A single-arm interventional trial.

Franziska Grundler¹, Magalie Viallon^2,3, Robin Mesnage^1,4

¹Buchinger Wilhelmi Clinic, Überlingen, Germany.

Frontiers in Nutrition

|December 5, 2022

Summary

Long-term fasting (LF) and reintroducing food significantly alter body composition, organ volume, and metabolic profiles. This study investigates these multi-systemic effects in humans, providing insights into tissue remodeling during fasting.

Keywords:

lipoprotein metabolism long-term fasting magnetic resonance imaging (MRI)metabolomics microbiome organ size protein utilisation

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Area of Science:

Metabolic and signaling pathways
Human physiology
Nutritional science

Background:

Fasting impacts metabolic pathways, influencing lifespan in animal models.
Human fasting metabolism relies on various metabolites, but organ contributions and tissue remodeling are not fully understood.
Changes in organ volume and composition during fasting require further exploration.

Purpose of the Study:

To investigate the multi-systemic effects of long-term fasting (LF) and food reintroduction in humans.
To analyze changes in body composition, organ volume, lipid metabolism, protein utilization, blood metabolites, and gut microbiome.
To provide a comprehensive understanding of tissue remodeling processes during fasting and refeeding.

Main Methods:

Prospective, single-arm trial with 100 subjects undergoing 9±3 day fasting periods (250 kcal/day).
Assessment of organ and bone composition, blood lipid profiles, HDL transport, PBMC metabolomics, protein persulfidation, and gut microbiome.
Detailed analysis using MRI and spectroscopy for 32 subjects, with follow-up examinations at 1 and 4 months.

Main Results:

Fasting induces significant changes in body composition and organ volumes.
Metabolic profiles, including blood lipids and gut microbiome, are substantially altered.
Tissue remodeling and metabolic adaptations occur during fasting and subsequent refeeding.

Conclusions:

Long-term fasting profoundly impacts human physiology, affecting body composition and organ function.
Understanding these systemic changes is crucial for optimizing health and longevity interventions.
This study provides novel insights into the complex adaptations to fasting and refeeding in humans.