Feeding During Phases of Altered Mitochondrial Activity: A Theory

Liam McKeever, Marcelo Bonini, Carol Braunschweig*

*Corresponding author for this work

Research output: Contribution to journalReview article

5 Scopus citations


Decisions surrounding the timing and dosing of nutrition support are made for thousands of ICU patients daily and yet remain a topic of controversy. Nutrition support designed to replenish resting energy expenditure (REE) early in critical illness has led to worse clinical outcomes in at least three recent prospective randomized clinical trials. Producing sufficient energy from nutrient substrates requires use of the mitochondrial electron transport chain (ETC). This process is functionally linked to the creation of a tightly regulated series of chemical messengers known as reactive oxygen species (ROS). In health, ROS are kept at low levels by a system of mitochondrial/cellular enzymes and antioxidants, allowing ROS to act as a signal for the redox health of the cell. In inflammatory conditions, however, this system is altered, leading to changes in the physiologic function of the ETC such that its usage produces greater ROS per unit of substrate. This increased ROS is capable of deactivating antioxidant systems, as well as activating further ROS-producing pathways and stimulating localized inflammatory activity. We propose that exacerbation of this process at this time by the forced influx of exogenously acquired nutrient substrates leads to mitochondrial damage, amplified ROS production, increased inflammation, decreased ATP-productive capacity, and, eventually, the death of the cell by either apoptosis or necrosis. Knowledge of this process is vital to determining the safe dosing and timing of nutrition support in the ICU. It is possible that the physiologic cost of meeting the REE under these conditions of mitochondrial stress may simply be too high. This paper details the proposed process by which inappropriately timed feeding in critically ill patients may damage the very mitochondria required for its utilization.

Original languageEnglish (US)
Pages (from-to)855-863
Number of pages9
JournalJournal of Parenteral and Enteral Nutrition
Issue number5
StatePublished - Jul 2018
Externally publishedYes


  • critical illness
  • inflammation
  • nutrition support practice
  • reactive oxygen species free radicals

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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