Effects of seven days’ fasting on physical performance and metabolic adaptation during exercise in humans

Kristoffer J. Kolnes, Emelie T.F. Nilsen, Steffen Brufladt, Allison M. Meadows, Per B. Jeppesen, Øyvind Skattebo, Egil I. Johansen, Jesper B. Birk, Kurt Højlund, Janne Hingst, Bjørn S. Skålhegg, Rasmus Kjøbsted, Julian L. Griffin, Anders J. Kolnes, Stephen O’Rahilly, Jørgen F.P. Wojtaszewski, Jørgen Jensen*

*Corresponding author for this work

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Abstract

Humans have, throughout history, faced periods of starvation necessitating increased physical effort to gather food. To explore adaptations in muscle function, 13 participants (7 males and 6 females) fasted for seven days. They lost 4.6 ± 0.3 kg lean and 1.4 ± 0.1 kg fat mass. Maximal isometric and isokinetic strength remained unchanged, while peak oxygen uptake decreased by 13%. Muscle glycogen was halved, while expression of electron transport chain proteins was unchanged. Pyruvate dehydrogenase kinase 4 (PDK4) expression increased 13-fold, accompanied by inhibitory pyruvate dehydrogenase phosphorylation, reduced carbohydrate oxidation and decreased exercise endurance capacity. Fasting had no impact on 5’ AMP-activated protein kinase (AMPK) activity, challenging its proposed role in muscle protein degradation. The participants maintained muscle strength and oxidative enzymes in skeletal muscle during fasting but carbohydrate oxidation and high-intensity endurance capacity were reduced.

Original languageEnglish
Article number122
JournalNature Communications
Volume16
Issue number1
Number of pages14
ISSN2041-1723
DOIs
Publication statusPublished - 2025

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