title: Leucine as a treatment for muscle wasting: a critical review.
abstract: Amino acids are potent modulators of protein turnover and skeletal muscle cells are highly sensitive to changes in amino acid availability. During amino acid abundance increased activity of mTORC1 drives protein synthesis and growth. In skeletal muscle, it has been clearly demonstrated that of all the amino acids, leucine is the most potent stimulator of mTORC1 and protein synthesis in vitro and in vivo. As such, leucine has received considerable attention as a potential pharmaconutrient for the treatment of numerous muscle wasting conditions. However, despite a multitude of studies showing enhanced acute protein synthesis with leucine or leucine-rich supplements in healthy individuals, additional leucine intake does not necessarily enhance protein synthesis during muscle wasting conditions. In addition, long-term, placebo controlled, iso-caloric studies in humans consistently show no beneficial effect of leucine supplementation on skeletal muscle mass or function. This review, critically evaluates the therapeutic potential of leucine to attenuate the skeletal muscle wasting associated with ageing, cancer and immobilization/bed rest. It also highlights the impact of inflammation on amino acid sensing, mTORC1 activation and stimulation of protein synthesis and challenges the underlying hypothesis that the acute activation of mTORC1 and stimulation of protein synthesis by leucine increases in muscle mass over time. We conclude that leucine, as a standalone nutritional intervention, is not effective in the prevention of muscle wasting. Future work should focus on identifying and utilizing other nutrients or treatments that sensitize skeletal muscle to leucine, thereby enhancing its therapeutic potential for muscle wasting conditions.
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ham
authors.forename: Marissa K
authors.initials: MK
authors.lastname: Caldow
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Lynch
authors.forename: René
authors.initials: R
authors.lastname: Koopman
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D006801:Humans; D007930:Leucine / Q000494:pharmacology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009133:Muscular Atrophy / Q000188:drug therapy*; D014176:Protein Biosynthesis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D009124:Muscle Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D007930:Leucine