Abstract
Glycogen depletion, nutritional ketosis and exercise fatigue: novel assessment methods and psychobiological mechanisms Glycogen is a multibranched polysaccharide of glucose that serves as a primary energy reserve, particularly in skeletal muscle, for ATP production. During exercise, glycogen is progressively degraded according to the duration and intensity of physical activity. It is well established that glycogen concentration is closely linked to fatigue during exercise. According to the peripheral fatigue model, when glycogen is depleted, it limits ATP resynthesis at the rate required to sustain muscular effort. More recently, muscle glycogen has also been proposed to play a structural role, as its depletion may impair calcium ion release from the sarcoplasmic reticulum. In contrast, little research has explored potential central mechanisms of fatigue. According to the psychobiological model (PBM), glycogen depletion increases central motor drive to the locomotor muscles, which is perceived as greater effort and interacts with motivational factors to determine when individuals slow down or stop endurance exercise. Being able to quantify glycogen stores non-invasively would be crucial for optimizing exercise and nutritional strategies in athletes. However, other pathways may also influence central fatigue. One such factor is the ketogenic diet (KD), a nutritional approach based on a markedly reduced carbohydrate intake (<5%). While intense exercise depletes glycogen stores locally, KD induces systemic effects, including the production of ketone bodies, neurotrophic factors (e.g., BDNF), and alterations in molecules such as kynurenine, all of which can directly affect brain function. Main Hypothesis: At equal levels of muscle glycogen, individuals following a KD will experience reduced central fatigue during exercise due to the action of ketone bodies. Using exercise as a model of glycogen depletion, we will test this hypothesis in healthy adults through the following specific aims: ● Aim 1: Develop and validate a non-invasive method to measure changes in glycogen concentration. We hypothesize that phase-sensitive single-frequency bioimpedance (SF-BIA) can detect changes in body water following carbohydrate loading or depletion, thereby estimating glycogen localization in muscle cells. ● Aim 2: Test whether nutritional ketosis improves endurance performance in humans after glycogen depletion. We hypothesize that, once exercise eliminates any initial differences in glycogen caused by KD, nutritional ketosis will enhance endurance performance. ● Aim 3: Explore the psychobiological mechanisms underlying the hypothesized performance benefits of nutritional ketosis. We hypothesize that, beyond its metabolic effects (i.e., keto-adaptation), nutritional ketosis improves performance by reducing cortical activity and perceived fatigability during endurance exercise.
Project details
Unibo Team Leader: Samuele Maria Marcora
Unibo involved Department/s:
Dipartimento di Scienze per la Qualità della Vita
Coordinator:
Università degli Studi di PADOVA(Italy)
Total Unibo Contribution: Euro (EUR) 138.991,00
Project Duration in months: 24
Start Date:
30/11/2023
End Date:
28/02/2026
