Tetlow, Nicholas; Centre for Peri-operative Medicine, Division of Surgery,  University College London, London, UK.;
Whittle, John

Annals of nutrition & metabolism,2025 Mar 21

• Background: Metabolic flexibility, the capacity to switch between energy sources in response to changing physiological demands, emerges as a critical determinant of perioperative resilience. In the context of surgery, where metabolic demands are high and energy homeostasis is disrupted, patients with metabolic inflexibility may experience worse outcomes due to impaired immune responses and heightened insulin resistance, resulting in prolonged recovery times.
• Summary: This article explores the implications of metabolic flexibility in the perioperative period and examines the potential for prehabilitation strategies, such as targeted exercise and nutritional interventions, to improve patient readiness for surgery. Cardiopulmonary exercise testing is discussed as a valuable assessment tool for metabolic flexibility, capable of providing insights into a patient’s fuel adaptability and overall metabolic health preoperatively. Evidence suggests that targeted exercise and nutritional strategies can enhance mitochondrial function, improve nutrient-sensing pathways, and increase substrate oxidation, which may reduce perioperative complications and support immune resilience.
• Key Messages: Future research should prioritise refining methods to identify metabolically inflexible patients and tailoring prehabilitation interventions to optimise metabolic flexibility. Enhancing perioperative metabolic readiness is important for populations vulnerable to metabolic dysfunction, such as those with obesity, diabetes, and cancer. Aligning metabolic optimisation with surgical recovery demands may help establish new standards in perioperative care and improve patient outcomes.