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

Kristoffer J. Kolnes, Eva Nilsen, Steffen Brufladt, Allison M. Meadows, Per Bendix Jeppesen, Øyvind Skattebo, Egil I. Johansen, Jesper B. Birk, Kurt Højlund, Janne R. Hingst, Bjørn Steen Skålhegg, Rasmus Kjøbsted, Julian L. Griffin, Anders J. Kolnes, Stephen O’Rahilly, Jørgen F. P. Wojtaszewski, Jørgen Jensen

2025Nature Communications32 citationsDOIOpen Access PDF

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.

Topics & Concepts

Adaptation (eye)Metabolic adaptationPhysical exerciseMedicinePhysiologyInternal medicineEndocrinologyBiologyMetabolismNeuroscienceDiet and metabolism studiesDietary Effects on HealthAdipose Tissue and Metabolism
Effects of seven days’ fasting on physical performance and metabolic adaptation during exercise in humans | Litcius