Mitochondrial Dysfunction in Critical Illness: Implications for Nutritional Therapy

  • Stephen A. McClaveEmail author
  • Paul E. Wischmeyer
  • Keith R. Miller
  • Arthur R. H. van Zanten
Gastroenterology, Critical Care, and Lifestyle Medicine (SA McClave, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Gastroenterology, Critical Care, and Lifestyle Medicine


Purpose of the Review

This paper will review the evidence for mitochondrial dysfunction in critical illness, describe the mechanisms which lead to multiple organ failure, and detail the implications of this pathophysiologic process on nutritional therapy.

Recent Findings

Mitochondria are particularly sensitive to increased oxidative stress in critical illness. The functional and structural abnormalities which occur in this organelle contribute further to the excessive production of reactive oxygen species and the reduction in generation of adenosine triphosphate (ATP). To reduce metabolic demand, mitochondrial dysfunction develops (a process likened to hibernation), which helps sustain the life of the cell at a cost of organ system failure. Aggressive feeding in the early phases of critical illness might inappropriately increase demand at a time when ATP production is limited, further jeopardizing cell survival and potentiating the processes leading to multiple organ failure.


Several potential therapies exist which would promote mitochondrial function in the intensive care setting through support of autophagy, antioxidant defense systems, and the biogenesis and recovery of the organelle itself. Nutritional therapy should supplement micronutrients required in the mitochondrial metabolic pathways and provide reduced delivery of macronutrients through slower advancement of feeding in the early phases of critical illness. A better understanding of mitochondrial dysfunction in the critically ill patient should lead to more innovative therapies in the future.


Mitochondrial failure Critical illness Nutritional therapy Multiple organ failure 


Compliance with Ethical Standards

Conflict of Interest

Stephen A. McClave declares that he has no conflict of interest.

Paul E. Wischmeyer has received research funding from Baxter, Abbott Laboratories, Fresenius Kabi, the National Institutes of Health (NIH), and Nutricia; has received compensation from Baxter, Abbott Laboratories, and Nutricia for service as a consultant; and has received compensation from Abbott Laboratories and Nutricia for participating in Continuing Medical Education (CME) Speaking programs.

Keith R. Miller has received salary support from Nestlé Nutrition through its Nutritional Educational Fellowship.

Arthur R.H. van Zanten has received research funding from Nutricia, Cardinal Health, and Mermaid Pharmaceuticals GmbH; has received compensation from Baxter, Fresenius Kabi, and Nutricia for service as a consultant; and has received compensation from Baxter, Nestlé, Fresenius Kabi, B. Braun Medical, Inc., and Nutricia for participating in CME Speaking programs.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Stephen A. McClave
    • 1
    • 2
    Email author
  • Paul E. Wischmeyer
    • 3
  • Keith R. Miller
    • 4
  • Arthur R. H. van Zanten
    • 5
  1. 1.Department of MedicineUniversity of Louisville School of MedicineLouisvilleUSA
  2. 2.Division of Gastroenterology, Hepatology & NutritionUniversity of Louisville School of MedicineLouisvilleUSA
  3. 3.Department of AnesthesiologyDuke UniversityDurhamUSA
  4. 4.Department of SurgeryUniversity of Louisville School of MedicineLouisvilleUSA
  5. 5.Department of Intensive Care MedicineGelderse Vallei HospitalEdeThe Netherlands

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