Rethinking early nutrition in critical illness: The catabolic phase as a protective metabolic reset

Early nutritional support has long been considered a cornerstone of critical care, aiming to prevent catabolism and preserve lean body mass. However, large randomized clinical trials have challenged the assumption that achieving full caloric targets within 72 hours improves outcomes, particularly when parenteral nutrition is used. We propose that acute catabolism should not be regarded as a pathological dysfunction to be corrected, but rather as an adaptive response essential for cellular remodeling and metabolic recovery during critical illness.During acute stress, endogenous substrate mobilization and the activation of autophagy constitute a physiological survival mechanism that promotes repair and metabolic reset. The early administration of exogenous nutrients—especially through parenteral routes—may interfere with this adaptive process by suppressing autophagy and altering metabolic flexibility. Evidence from the EPaNIC, PEPaNIC, EDEN, and PermiT trials indicates that moderate caloric restriction during the initial days of illness is not harmful and may, in selected contexts, accelerate recovery. Reconsidering early nutrition through this physiological lens may prompt a paradigm shift—from “feeding early to avoid catabolism” to “respecting adaptive metabolism” in the critically ill. Recent ESPEN and ASPEN guidelines recommend a cautious initiation of enteral nutrition and discourage early parenteral feeding solely to close the caloric gap, implicitly recognizing a transient period of metabolic intolerance during the first days of critical illness. This concept opens the way for future studies exploring a metabolic tolerance window, in which nutritional therapy is modulated according to metabolic readiness rather than chronological time, integrating biomarkers and clinical outcomes to rigorously test this hypothesis.