L-Leucine (DB00149): A Comprehensive Monograph on its Pharmacology, Metabolism, and Clinical Utility

Executive Summary

L-Leucine is an essential, branched-chain amino acid (BCAA) that occupies a unique and central position in human physiology, functioning not only as a fundamental substrate for protein synthesis but also as a potent signaling molecule that governs cellular metabolism and growth. This monograph provides a comprehensive analysis of L-Leucine, synthesizing data from foundational biochemistry to contemporary clinical research. Its primary mechanism of action involves the direct activation of the mechanistic Target of Rapamycin Complex 1 (mTORC1), a master regulator of anabolism. This insulin-independent signaling capacity distinguishes Leucine from other amino acids and underpins its profound effects on skeletal muscle homeostasis, where it dually stimulates muscle protein synthesis and inhibits protein breakdown.

Clinically, Leucine is an indispensable component of parenteral nutrition formulations, where it is critical for maintaining nitrogen balance and preventing muscle catabolism in patients under severe metabolic stress. Its role as a therapeutic agent is most extensively studied in the context of age-related sarcopenia, where it can help overcome anabolic resistance, particularly when administered as part of a complete protein source and in conjunction with other key nutrients like Vitamin D. While widely used in sports nutrition to enhance muscle growth and recovery, its efficacy in this domain is highly dependent on the individual's training status and background protein intake. Investigational studies are exploring its potential in diverse areas, including obesity, rare hematological disorders, and post-traumatic recovery.