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S Stekovic, SJ Hofer, N Tripolt, MA Aon, P Royer, L Pein, JT Stadler, T Pendl, B Prietl, J Url, S Schroeder, J Tadic, T Eisenberg, C Magnes, M Stumpe, E Zuegner, N Bordag, R Riedl, A Schmidt, E Kolesnik, N Verheyen, A Springer, T Madl, F Sinner, R de Cabo, G Kroemer, B Obermayer-Pietsch, J Dengjel, H Sourij, TR Pieber and F Madeo
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 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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