Reconsidering the pre-eminence of dietary leucine and plasma leucinemia for predicting the stimulation of postprandial muscle protein synthesis rates

The regulation of postprandial muscle protein synthesis (MPS) with or without physical activity has been an intensely studied area within nutrition and physiology. The leucine content of dietary protein and the subsequent plasma leucinemia it elicits postingestion is often considered the primary drivers of the postprandial MPS response. This concept, generally known as the leucine "trigger" hypothesis, has also been adopted within more applied aspects of nutrition. Our view is that recent evidence is driving a more nuanced picture of the regulation of postprandial MPS by revealing a compelling dissociation between ingested leucine or plasma leucinemia and the magnitude of the postprandial MPS response. Much of this lack of coherence has arisen as experimental progress has demanded relevant studies move beyond reliance on isolated amino acids and proteins to use increasingly complex protein-rich meals, whole foods, and mixed meals. Our overreliance on the centrality of leucine in this field has been reflected in 2 recent systematic reviews. In this perspective, we propose a re-evaluation of the pre-eminent role of these leucine variables in the stimulation of postprandial MPS. We view the development of a more complex intellectual framework now a priority if we are to see continued progress concerning the mechanistic regulation of postprandial muscle protein turnover, but also consequential from an applied perspective when evaluating the value of novel dietary protein sources.