Tetlow, Nicholas; Whittle, John; (2025) Prehabilitation- Do we need metabolic flexibility. Annals of Nutrition and Metabolism pp. 1-22. 10.1159/000545266. (In press).

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Abstract

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. 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. Cardio-pulmonary exercise testing (CPET) 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. Future research should focus on refining methods to identify metabolically inflexible patients and tailoring prehabilitation interventions to optimise metabolic flexibility, particularly in populations vulnerable to metabolic dysfunction, such as those with obesity, diabetes, and cancer. This approach may establish new standards in perioperative care by aligning metabolic readiness with surgical recovery demands.

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