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Am J Clin Nutr 90: 1244-1251, 2009. First published September 23, 2009; doi:10.3945/ajcn.2008.27327
American Journal of Clinical Nutrition, doi:10.3945/ajcn.2008.27327
Vol. 90, No. 5, 1244-1251, November 2009

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© 2009 American Society for Clinical Nutrition

ORIGINAL RESEARCH COMMUNICATION

Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism1,2,3

Maarten R Soeters, Nicolette M Lammers, Peter F Dubbelhuis, Mariëtte Ackermans, Cora F Jonkers-Schuitema, Eric Fliers, Hans P Sauerwein, Johannes M Aerts and Mireille J Serlie

1 From the Departments of Endocrinology and Metabolism (MRS, NML, EF, HPS, and MJS) Medical Biochemistry (PFD and JMA) Clinical Chemistry Laboratory of Endocrinology (MTA), and Dietetics Academic Medical Center (CFJ-S) University of Amsterdam Amsterdam, Netherlands.

2 Nutricia Advanced Medical Nutrition (Zoetermeer, Netherlands) provided Nutridrink.

3 Address correspondence to MR Soeters, Department of Endocrinology and Metabolism, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, Netherlands. E-mail: m.r.soeters{at}amc.uva.nl.

Background: Intermittent fasting (IF) was shown to increase whole-body insulin sensitivity, but it is uncertain whether IF selectively influences intermediary metabolism. Such selectivity might be advantageous when adapting to periods of food abundance and food shortage.

Objective: The objective was to assess effects of IF on intermediary metabolism and energy expenditure.

Design: Glucose, glycerol, and valine fluxes were measured after 2 wk of IF and a standard diet (SD) in 8 lean healthy volunteers in a crossover design, in the basal state and during a 2-step hyperinsulinemic euglycemic clamp, with assessment of energy expenditure and phosphorylation of muscle protein kinase B (AKT), glycogen synthase kinase (GSK), and mammalian target of rapamycine (mTOR). We hypothesized that IF selectively increases peripheral glucose uptake and lowers proteolysis, thereby protecting protein stores.

Results: No differences in body weight were observed between the IF and SD groups. Peripheral glucose uptake and hepatic insulin sensitivity during the clamp did not significantly differ between the IF and SD groups. Likewise, lipolysis and proteolysis were not different between the IF and SD groups. IF decreased resting energy expenditure. IF had no effect on the phosphorylation of AKT but significantly increased the phosphorylation of glycogen synthase kinase. Phosphorylation of mTOR was significantly lower after IF than after the SD.

Conclusions: IF does not affect whole-body glucose, lipid, or protein metabolism in healthy lean men despite changes in muscle phosphorylation of GSK and mTOR. The decrease in resting energy expenditure after IF indicates the possibility of an increase in weight during IF when caloric intake is not adjusted. This study was registered at www.trialregister.nl as NTR1841.







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