Cell Metabolism
Volume 30, Issue 3, 3 September 2019, Pages 462-476.e5
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Clinical and Translational Report
Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans

Highlights

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For healthy, non-obese adults, ADF is safe to practice for several months

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4-week ADF decreases the body weight by 4.5% and improves the fat-to-lean ratio

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Cardiovascular parameters and the CVD risk are improved upon ADF

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ADF reduces T3 and periodically depletes amino acids, while increasing PUFAs

Summary

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 ¶¬-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.

Keywords

fasting
aging
clinical trial
intermittent fasting
caloric restriction
cardiovascular disease risk
body shape
fat distribution
triiodothyronine
RCT
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These authors contributed equally

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Senior author

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Lead Contact

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