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

Stekovic, Slaven; Hofer, Sebastian J.; Tripolt, Norbert; Aon, Miguel A.; Royer, Philipp; Pein, Lukas; Stadler, Julia T.; Pendl, Tobias; Prietl, Barbara; Url, Jasmin; Schroeder, Sabrina; Tadic, Jelena; Eisenberg, Tobias; Magnes, Christoph; Stumpe, Michael; Zuegner, Elmar; Bordag, Natalie; Riedl, Regina; Schmidt, Albrecht; Kolesnik, Ewald; Verheyen, Nicolas; Springer, Anna; Madl, Tobias; Sinner, Frank; de Cabo, Rafael; Kroemer, Guido; Obermayer-Pietsch, Barbara; Dengjel, Jom; Sourij, Harald; Pieber, Thomas R.; Madeo, Frank

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September 3, 2019

10.1016/j.cmet.2019.07.016

PMID: 31471173

Abstract:

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 beta-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.