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Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.

  • Stekovic S Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria.
  • Hofer SJ Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria; BioTechMed Graz, Graz 8010, Austria.
  • Tripolt N Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria.
  • Aon MA Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA; Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Royer P Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria.
  • Pein L Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria; Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria.
  • Stadler JT Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria; Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
  • Pendl T Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria.
  • Prietl B Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
  • Url J Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
  • Schroeder S Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria; BioTechMed Graz, Graz 8010, Austria.
  • Tadic J Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria.
  • Eisenberg T Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria; BioTechMed Graz, Graz 8010, Austria; NAWI Graz Central Lab Gracia, NAWI Graz, Graz, Austria.
  • Magnes C HEALTH Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz, Austria.
  • Stumpe M Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
  • Zuegner E HEALTH Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz, Austria.
  • Bordag N HEALTH Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz, Austria.
  • Riedl R Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria.
  • Schmidt A Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria.
  • Kolesnik E Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria.
  • Verheyen N Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria.
  • Springer A Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/, VI 8010 Graz, Austria.
  • Madl T BioTechMed Graz, Graz 8010, Austria; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/, VI 8010 Graz, Austria.
  • Sinner F Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; HEALTH Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz, Austria.
  • de Cabo R Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Kroemer G Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France; Cell Biology and Metabolomics platforms, Gustave Roussy Cancer Campus, Villejuif, France; INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden; Center of Systems Medicine, Chinese Academy of Science Sciences, Suzhou, China.
  • Obermayer-Pietsch B Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
  • Dengjel J Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland; Department of Dermatology, Medical Center, University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany.
  • Sourij H Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
  • Pieber TR Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria; HEALTH Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz, Austria.
  • Madeo F Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria; BioTechMed Graz, Graz 8010, Austria. Electronic address: frank.madeo@uni-graz.at.
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  • 2019-09-01
Published in:
  • Cell metabolism. - 2019
RCT
aging
body shape
caloric restriction
cardiovascular disease risk
clinical trial
fasting
fat distribution
intermittent fasting
triiodothyronine
3-Hydroxybutyric Acid
Adult
Aging
Biomarkers
Body Mass Index
Caloric Restriction
Energy Intake
Fasting
Fatty Acids, Unsaturated
Female
Healthy Aging
Healthy Volunteers
Humans
Intercellular Adhesion Molecule-1
Lipoproteins, LDL
Male
Middle Aged
Pilot Projects
Prospective Studies
Triiodothyronine
Weight Loss
English Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
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  • English
Open access status
bronze
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https://sonar.ch/global/documents/290145
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