Changes in Muscle Mass and Quality Mediate the Effect of High‐Calorie Intake on Clinical Outcomes
Abstract
Background Critically ill patients frequently experienced acquired muscle dysfunction, which adversely affects outcomes. The relationship between calorie intake, muscle dysfunction and outcomes remains unclear. This study aims to determine if early calorie intake affects patients' outcomes through changes in skeletal muscle mass or quality, and to explore changes in muscle structure and underlying molecular pathways using limb muscle biopsies in a piglet model. Methods This translational study combines data from a prospective observational study including critically ill patients and a 72‐h ventilated piglet model with early high calorie full enteral nutrition, both recording serial ultrasound measurements of limb muscle thickness and stiffness. Patients were classified into two trajectory groups based on thickness, stiffness and calorie intake. Adjusted mediation analysis quantified the effect of calorie intake on outcomes explained by muscle trajectories. The primary endpoint was ventilator‐free days at Day 28 (VFD28). In vivo limb muscle biopsies from piglets were analysed. Results Among 102 patients, 21% and 28% exhibited decreased thickness and stiffness by Day 7, respectively; 36% received high‐calorie intake at Day 7. Patients categorized into the ‘decreased trajectory group’ for both thickness and stiffness showed lower VFD28 ( p < 0.01) and longer ICU stay ( p < 0.01) compared to the ‘stable trajectory group’. High‐calorie intake was associated with significantly lower VFD28 (−8.7 days [−14.7 to −1.7]; p = 0.01), longer ICU stay ( p < 0.01) and higher ICU mortality ( p < 0.01). Decreased muscle trajectories mediated, respectively, 42% and 28% of the association between high‐calorie intake and VFD 28. The porcine model showed a limb muscle stiffness reduction associated with muscle fibre atrophy and increased intramuscular lipid content linked to decreased protein synthesis (IGF‐1 and myostatin downregulation), increased autophagy (ATG5, ATG7 and P62 increased activity) and impaired fatty acid metabolism (carnitine palmitoyltransferase 1B reduced expression). Conclusions This study demonstrates that early calorie intake in critically ill patients adversely affects muscle mass and quality, mediating negative outcomes. The porcine model helps elucidate underlying mechanisms, with early high‐calorie intake resulting in a metabolic oversupply state associated with metabolic disorders leading to muscle fibre atrophy and lipid accumulation. These results highlight the importance of targeted nutritional strategies to preserve muscle health in critically ill patients.
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BibTeX
@article{aarab2026changes,
title = {{Changes in Muscle Mass and Quality Mediate the Effect of High‐Calorie Intake on Clinical Outcomes}},
author = {Yassir Aarab and Fabrice Raynaud and Mathieu Capdevila and Aurelien Flatres and Gérald Hugon and Céline Lauret and Nicolas Molinari and Celia Vidal and Kada Klouche and Samir Jaber and Stefan Matecki and Boris Jung},
journal = {Journal of Cachexia, Sarcopenia and Muscle},
year = {2026},
month = aug,
doi = {10.1002/jcsm.70355},
url = {https://hal.science/hal-05717690v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Changes in Muscle Mass and Quality Mediate the Effect of High‐Calorie Intake on Clinical Outcomes
AU - Yassir Aarab
AU - Fabrice Raynaud
AU - Mathieu Capdevila
AU - Aurelien Flatres
AU - Gérald Hugon
AU - Céline Lauret
AU - Nicolas Molinari
AU - Celia Vidal
AU - Kada Klouche
AU - Samir Jaber
AU - Stefan Matecki
AU - Boris Jung
PY - 2026
DA - 2026/08/12
JO - Journal of Cachexia, Sarcopenia and Muscle
DO - 10.1002/jcsm.70355
UR - https://hal.science/hal-05717690v1
AB - Background Critically ill patients frequently experienced acquired muscle dysfunction, which adversely affects outcomes. The relationship between calorie intake, muscle dysfunction and outcomes remains unclear. This study aims to determine if early calorie intake affects patients' outcomes through changes in skeletal muscle mass or quality, and to explore changes in muscle structure and underlying molecular pathways using limb muscle biopsies in a piglet model. Methods This translational study combines data from a prospective observational study including critically ill patients and a 72‐h ventilated piglet model with early high calorie full enteral nutrition, both recording serial ultrasound measurements of limb muscle thickness and stiffness. Patients were classified into two trajectory groups based on thickness, stiffness and calorie intake. Adjusted mediation analysis quantified the effect of calorie intake on outcomes explained by muscle trajectories. The primary endpoint was ventilator‐free days at Day 28 (VFD28). In vivo limb muscle biopsies from piglets were analysed. Results Among 102 patients, 21% and 28% exhibited decreased thickness and stiffness by Day 7, respectively; 36% received high‐calorie intake at Day 7. Patients categorized into the ‘decreased trajectory group’ for both thickness and stiffness showed lower VFD28 ( p < 0.01) and longer ICU stay ( p < 0.01) compared to the ‘stable trajectory group’. High‐calorie intake was associated with significantly lower VFD28 (−8.7 days [−14.7 to −1.7]; p = 0.01), longer ICU stay ( p < 0.01) and higher ICU mortality ( p < 0.01). Decreased muscle trajectories mediated, respectively, 42% and 28% of the association between high‐calorie intake and VFD 28. The porcine model showed a limb muscle stiffness reduction associated with muscle fibre atrophy and increased intramuscular lipid content linked to decreased protein synthesis (IGF‐1 and myostatin downregulation), increased autophagy (ATG5, ATG7 and P62 increased activity) and impaired fatty acid metabolism (carnitine palmitoyltransferase 1B reduced expression). Conclusions This study demonstrates that early calorie intake in critically ill patients adversely affects muscle mass and quality, mediating negative outcomes. The porcine model helps elucidate underlying mechanisms, with early high‐calorie intake resulting in a metabolic oversupply state associated with metabolic disorders leading to muscle fibre atrophy and lipid accumulation. These results highlight the importance of targeted nutritional strategies to preserve muscle health in critically ill patients.
SN - 2190-5991
SN - 2190-6009
ER -