Fig. 1

Selected mechanisms explaining the lack of benefit by early full feeding in critical illness. Evoked by the stress response to severe illness, anabolic resistance occurs, whereby muscle catabolism and hepatic gluconeogenesis cannot be counteracted by providing macronutrients, unlike in normal health. Providing extra macronutrients in such condition increases the risk of overfeeding, manifested as hyperglycemia, hypertriglyceridemia, liver dysfunction and hyperuremia by catabolism of extra provided amino acids. In addition, continuous artificial nutrition continuously suppresses autophagy and ketogenesis as potentially important repair pathways. The time when anabolic resistance ceases and the condition reverses into metabolic feeding responsiveness cannot be predicted or monitored at the bedside. Theoretically, feeding responsiveness may undergo dynamic changes over time, and the timing of such changes likely differs between patients