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

Franziska Grundler; Magalie Viallon; Robin Mesnage; Massimiliano Ruscica; Clemens von Schacky; Frank Madeo; Sebastian J Hofer; Sarah J Mitchell; Pierre Croisille; Françoise Wilhelmi de Toledo

doi:10.3389/fnut.2022.951000

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

Front Nutr. 2022 Nov 17:9:951000. doi: 10.3389/fnut.2022.951000. eCollection 2022.

Authors

Franziska Grundler¹, Magalie Viallon^{2

3}, Robin Mesnage^{1

4}, Massimiliano Ruscica⁵, Clemens von Schacky⁶, Frank Madeo^{7

8

9}, Sebastian J Hofer^{7

8

9}, Sarah J Mitchell¹⁰, Pierre Croisille^{2

3}, Françoise Wilhelmi de Toledo¹

Affiliations

¹ Buchinger Wilhelmi Clinic, Überlingen, Germany.
² UJM-Saint-Etienne, INSA, CNRS UMR 5520, INSERM U1206, CREATIS, F-42023, Université de Lyon, Saint-Étienne, France.
³ Department of Radiology, University Hospital Saint-Étienne, Saint-Étienne, France.
⁴ Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
⁵ Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
⁶ Omegametrix, Martinsried, Germany.
⁷ Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
⁸ BioHealth Graz, Graz, Austria.
⁹ BioTechMed Graz, Graz, Austria.
¹⁰ Department of Health Sciences and Technology, ETH Zürich, Schwerzenbach, Switzerland.

Abstract

Fasting provokes fundamental changes in the activation of metabolic and signaling pathways leading to longer and healthier lifespans in animal models. Although the involvement of different metabolites in fueling human fasting metabolism is well known, the contribution of tissues and organs to their supply remains partly unclear. Also, changes in organ volume and composition remain relatively unexplored. Thus, processes involved in remodeling tissues during fasting and food reintroduction need to be better understood. Therefore, this study will apply state-of-the-art techniques to investigate the effects of long-term fasting (LF) and food reintroduction in humans by a multi-systemic approach focusing on changes in body composition, organ and tissue volume, lipid transport and storage, sources of protein utilization, blood metabolites, and gut microbiome profiles in a single cohort. This is a prospective, single-arm, monocentric trial. One hundred subjects will be recruited and undergo 9 ± 3 day-long fasting periods (250 kcal/day). We will assess changes in the composition of organs, bones and blood lipid profiles before and after fasting, as well as high-density lipoprotein (HDL) transport and storage, untargeted metabolomics of peripheral blood mononuclear cells (PBMCs), protein persulfidation and shotgun metagenomics of the gut microbiome. The first 32 subjects, fasting for 12 days, will be examined in more detail by magnetic resonance imaging (MRI) and spectroscopy to provide quantitative information on changes in organ volume and function, followed by an additional follow-up examination after 1 and 4 months. The study protocol was approved by the ethics board of the State Medical Chamber of Baden-Württemberg on 26.07.2021 and registered at ClinicalTrials.gov (NCT05031598). The results will be disseminated through peer-reviewed publications, international conferences and social media.

Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05031598].

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

Associated data

ClinicalTrials.gov/NCT05031598