Energy, Proteins, and Amino Acids in Hypercatabolic Disease States: Moving Beyond a Calorie-Centered Paradigm

Acute and chronic diseases such as sepsis, trauma, cancer cachexia, heart failure, COPD, and organ failure share a common metabolic feature: the hypercatabolic state (HCS). HCS is driven by systemic inflammation and neuroendocrine activation, leading to a marked increase in basal metabolic rate, a profound energy deficit, and accelerated skeletal muscle proteolysis with concomitant anabolic resistance. In this context, skeletal muscle functions as a reservoir of amino acids (AAs), which are mobilized to sustain energy production, gluconeogenesis, and biosynthetic processes essential for immune and organ function. If inadequately addressed, this metabolic adaptation results in loss of lean body mass, sarcopenia, and cachexia, conditions that independently worsen clinical outcomes. Standardized protein recommendations are often insufficient due to the high interindividual variability of metabolic responses in HCS. Moreover, AAs are not metabolically equivalent: beyond serving as substrates, they act as signaling molecules (metabokines) that regulate key metabolic pathways. This underscores the limitation of calorie-centered nutritional strategies, which fail to capture the functional and regulatory roles of proteins and AAs. This narrative review highlights the need for an integrated nutritional paradigm that jointly considers energy intake, protein quality, AAs composition, and individual physiology to optimize metabolic management in hypercatabolic conditions.