Prehabilitation- Do We Need Metabolic Flexibility
Open accessAbstract
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.
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This cycle leads to increase in ROS production, which can damage cellular components but also play essential roles in signaling processes such as mitophagy and apoptosis in senescent cells.
“This cycle also leads to an increase in the production of reactive oxygen species (ROS), which, while capable of damaging cellular components, including membrane lipids, structural and enzymatic proteins, and both nuclear and mitochondrial DNA, also play essential roles in signaling processes such as mitophagy and apoptosis in senescent cells [16].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [16]
The section “Enhancing Metabolic Flexibility with Exercise and Nutrition in Prehabilitation” (page unavailable) discusses mitochondrial adaptation and metabolic signaling, but does not address ROS production, cellular damage, or ROS signaling in mitophagy and apoptosis of senescent cells. Searches for “ROS,” “mitophagy,” and the claimed cellular effects found no passage supporting the attributed point. (LLM, conf=0.72)
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References 55 · Cited by 6
- Authors
- Tetlow, N., & Whittle, J.
- Affiliations
- University College London Hospitals NHS Foundation Trust (GB)
- Corresponding author
- Whittle, John
- Venue
- Annals of Nutrition and Metabolism
- Publisher
- S. Karger AG
- Published
- 2025-03-21
- Volume
- 81
- Issue
- 4
- Pages
- 223-233
- ISSN
- 0250-6807 (ISSN-L)
- 1421-9697
- PMC
- PMC12060803
- OpenAlex
- W4408694606
- Cited by
- 6
- References
- 55
- Citations by year
- 2026: 4 · 2025: 2
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Annals of Nutrition and Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Enhanced Recovery After Surgery
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac, Anesthesia and Surgical Outcomes
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Keywords
- metabolic flexibility, prehabilitation, perioperative care, metabolic inflexibility, cardiopulmonary exercise testing, dietary intervention, mitochondrial function, substrate oxidation, insulin resistance, immune resilience, postoperative recovery, obesity, diabetes mellitus, cancer
- MeSH terms
- Preoperative Exercise, Energy Metabolism, Exercise Test, Humans, Insulin Resistance, Preoperative Care
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