Leucine

Last Updated: September 28 2022

Leucine is a branced-chain amino acid (BCAA) and potent nutrient- based signal to activate protein synthesis.

Leucine is most often used for

Summary

Leucine, along with isoleucine and valine, is one of the three branched-chain amino acids (BCAAs). Out of all the amino acids, leucine is the most potent activator of protein synthesis. Cells are able to sense leucine levels, and in response turn on protein synthesis via the enzyme protein mammalian target of rapamycin (mTOR), a master-regulator of protein synthesis.

Given the well-established protein-synthesis activating properties of leucine, a number of human trials have been conducted to determine whether adding supplemental leucine to various protein sources can augment muscle protein synthesis (MPS), particularly in older adults.

Anabolic resistance is a well-established phenomenon during aging, with cells becoming more resistant to turning on protein synthesis. This can be partly ameliorated with extra leucine, as research indicates that older adults need twice as much leucine compared to younger adults for similar activation of MPS.[1]

This increased leucine requirement for MPS in older adults can be partially explained by increased retention of orally ingested leucine in the gut, which is retained twice as much compared to young adults,[2] limiting the amount of leucine that makes it into the blood stream. Resistance to leucine-stimulated protein synthesis also occurs at the cellular level in aging cells.

Results in both younger and older adults have shown that supplementation with leucine enhances the MPS response,[3][4][5][6] namely when a suboptimal dose of protein is consumed.

In a study that compared a low (6 g) dose of whey protein alongside 3 or 5 g of extra leucine to 25 g of whey protein alone in younger adults, the low dose of whey protein plus 5 g of leucine meal stimulated MPS to a similar, but lesser extent than 25 g of whey protein.[3] Another study in younger adults compared the same 25 g dose of whey protein to 6 g of whey protein with an amount of leucine equivalent to 25 g of whey protein and found that only the group that consumed 25 g of whey protein had elevated MPS 3 to 5 hours post-exercise.[4]

Despite the positive effects of leucine on acute rates of MPS, long-term supplementation has largely failed to augment increases in muscle mass and strength in older adults.[7] Further research is needed to determine whether supplementation with leucine can augment muscle mass accretion in older adults with suboptimal protein intake.

Research suggests that supplemental leucine can augment muscle protein synthesis when a suboptimal dose of protein is consumed, but supplemental leucine will not confer additional benefit if a protein bolus sufficient to maximally stimulate muscle protein synthesis is consumed.

What else is Leucine known as?
Note that Leucine is also known as:
  • L-Leucine
Leucine should not be confused with:
Dosage information

Leucine tends to be supplemented in the 2,000-5,000mg range for acute usage.

It tends to be taken either in a fasted state or alongside meals with an inhernetly low protein content (or protein sources that are low in leucine).

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      References
      1.^Isabelle Rieu, Michèle Balage, Claire Sornet, Christophe Giraudet, Estelle Pujos, Jean Grizard, Laurent Mosoni, Dominique DardevetLeucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemiaJ Physiol.(2006 Aug 15)
      2.^Y Boirie, P Gachon, B BeaufrèreSplanchnic and whole-body leucine kinetics in young and elderly menAm J Clin Nutr.(1997 Feb)
      3.^Churchward-Venne TA, Breen L, Di Donato DM, Hector AJ, Mitchell CJ, Moore DR, Stellingwerff T, Breuille D, Offord EA, Baker SK, Phillips SMLeucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trialAm J Clin Nutr.(2014 Feb)
      4.^Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SMSupplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in menJ Physiol.(2012 Jun 1)
      5.^Caoileann H Murphy, Nelson I Saddler, Michaela C Devries, Chris McGlory, Steven K Baker, Stuart M PhillipsLeucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover studyAm J Clin Nutr.(2016 Dec)
      6.^Benjamin T Wall, Henrike M Hamer, Anneke de Lange, Alexandra Kiskini, Bart B L Groen, Joan M G Senden, Annemie P Gijsen, Lex B Verdijk, Luc J C van LoonLeucine co-ingestion improves post-prandial muscle protein accretion in elderly menClin Nutr.(2013 Jun)
      8.^Holmes HC, Burns SP, Chalmers RA, Bain MS, Iles RAKetogenic flux from lipids and leucine, assessment in 3-hydroxy-3-methylglutaryl CoA lyase deficiencyBiochem Soc Trans.(1995 Aug)
      13.^Wullschleger S, Loewith R, Hall MNTOR signaling in growth and metabolismCell.(2006 Feb 10)
      14.^Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DMmTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machineryCell.(2002 Jul 26)
      15.^Dann SG, Selvaraj A, Thomas GmTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancerTrends Mol Med.(2007 Jun)
      16.^Byfield MP, Murray JT, Backer JMhVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinaseJ Biol Chem.(2005 Sep 23)
      17.^Nobukuni T, Joaquin M, Roccio M, Dann SG, Kim SY, Gulati P, Byfield MP, Backer JM, Natt F, Bos JL, Zwartkruis FJ, Thomas GAmino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinaseProc Natl Acad Sci U S A.(2005 Oct 4)
      18.^Greiwe JS, Kwon G, McDaniel ML, Semenkovich CFLeucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscleAm J Physiol Endocrinol Metab.(2001 Sep)
      19.^Blomstrand E, Eliasson J, Karlsson HK, Köhnke RBranched-chain amino acids activate key enzymes in protein synthesis after physical exerciseJ Nutr.(2006 Jan)
      22.^Gulati P, Gaspers LD, Dann SG, Joaquin M, Nobukuni T, Natt F, Kozma SC, Thomas AP, Thomas GAmino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34Cell Metab.(2008 May)
      23.^Mercan F, Lee H, Kolli S, Bennett AMNovel role for SHP-2 in nutrient-responsive control of S6 kinase 1 signalingMol Cell Biol.(2013 Jan)
      24.^Fornaro M, Burch PM, Yang W, Zhang L, Hamilton CE, Kim JH, Neel BG, Bennett AMSHP-2 activates signaling of the nuclear factor of activated T cells to promote skeletal muscle growthJ Cell Biol.(2006 Oct 9)
      25.^Zito CI, Qin H, Blenis J, Bennett AMSHP-2 regulates cell growth by controlling the mTOR/S6 kinase 1 pathwayJ Biol Chem.(2007 Mar 9)
      28.^Verdin E, Hirschey MD, Finley LW, Haigis MCSirtuin regulation of mitochondria: energy production, apoptosis, and signalingTrends Biochem Sci.(2010 Dec)
      29.^Bordone L, Guarente LCalorie restriction, SIRT1 and metabolism: understanding longevityNat Rev Mol Cell Biol.(2005 Apr)
      30.^Guarente L, Picard FCalorie restriction--the SIR2 connectionCell.(2005 Feb 25)
      33.^Bruckbauer A, Gouffon J, Rekapalli B, Zemel MBThe effects of dairy components on energy partitioning and metabolic risk in mice: a microarray studyJ Nutrigenet Nutrigenomics.(2009)
      37.^Uberall F, Hellbert K, Kampfer S, Maly K, Villunger A, Spitaler M, Mwanjewe J, Baier-Bitterlich G, Baier G, Grunicke HHEvidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeletonJ Cell Biol.(1999 Feb 8)
      38.^Nishitani S, Matsumura T, Fujitani S, Sonaka I, Miura Y, Yagasaki KLeucine promotes glucose uptake in skeletal muscles of ratsBiochem Biophys Res Commun.(2002 Dec 20)
      40.^Tessari P, Inchiostro S, Biolo G, Duner E, Nosadini R, Tiengo A, Crepaldi GHyperaminoacidaemia reduces insulin-mediated glucose disposal in healthy manDiabetologia.(1985 Nov)
      44.^O'Neill HMAMPK and Exercise: Glucose Uptake and Insulin SensitivityDiabetes Metab J.(2013 Feb)
      46.^Tremblay F, Brûlé S, Hee Um S, Li Y, Masuda K, Roden M, Sun XJ, Krebs M, Polakiewicz RD, Thomas G, Marette AIdentification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistanceProc Natl Acad Sci U S A.(2007 Aug 28)
      48.^Haruta T, Uno T, Kawahara J, Takano A, Egawa K, Sharma PM, Olefsky JM, Kobayashi MA rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1Mol Endocrinol.(2000 Jun)
      53.^Yang J, Wong RK, Park M, Wu J, Cook JR, York DA, Deng S, Markmann J, Naji A, Wolf BA, Gao ZLeucine regulation of glucokinase and ATP synthase sensitizes glucose-induced insulin secretion in pancreatic beta-cellsDiabetes.(2006 Jan)
      54.^Yang J, Wong RK, Wang X, Moibi J, Hessner MJ, Greene S, Wu J, Sukumvanich S, Wolf BA, Gao ZLeucine culture reveals that ATP synthase functions as a fuel sensor in pancreatic beta-cellsJ Biol Chem.(2004 Dec 24)
      55.^Bränström R, Efendić S, Berggren PO, Larsson ODirect inhibition of the pancreatic beta-cell ATP-regulated potassium channel by alpha-ketoisocaproateJ Biol Chem.(1998 Jun 5)
      57.^Malaisse WJ, Hutton JC, Carpinelli AR, Herchuelz A, Sener AThe stimulus-secretion coupling of amino acid-induced insulin release: metabolism and cationic effects of leucineDiabetes.(1980 Jun)
      58.^Devedjian JC, Pujol A, Cayla C, George M, Casellas A, Paris H, Bosch FTransgenic mice overexpressing alpha2A-adrenoceptors in pancreatic beta-cells show altered regulation of glucose homeostasisDiabetologia.(2000 Jul)
      59.^Rosengren AH, Jokubka R, Tojjar D, Granhall C, Hansson O, Li DQ, Nagaraj V, Reinbothe TM, Tuncel J, Eliasson L, Groop L, Rorsman P, Salehi A, Lyssenko V, Luthman H, Renström EOverexpression of alpha2A-adrenergic receptors contributes to type 2 diabetesScience.(2010 Jan 8)
      60.^Shimodahira M, Fujimoto S, Mukai E, Nakamura Y, Nishi Y, Sasaki M, Sato Y, Sato H, Hosokawa M, Nagashima K, Seino Y, Inagaki NRapamycin impairs metabolism-secretion coupling in rat pancreatic islets by suppressing carbohydrate metabolismJ Endocrinol.(2010 Jan)
      61.^Fraenkel M, Ketzinel-Gilad M, Ariav Y, Pappo O, Karaca M, Castel J, Berthault MF, Magnan C, Cerasi E, Kaiser N, Leibowitz GmTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetesDiabetes.(2008 Apr)
      63.^K Hara, K Yonezawa, Q P Weng, M T Kozlowski, C Belham, J AvruchAmino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanismJ Biol Chem.(1998 Jun 5)
      64.^X Wang, L E Campbell, C M Miller, C G ProudAmino acid availability regulates p70 S6 kinase and multiple translation factorsBiochem J.(1998 Aug 15)
      65.^H L Fox, P T Pham, S R Kimball, L S Jefferson, C J LynchAmino acid effects on translational repressor 4E-BP1 are mediated primarily by L-leucine in isolated adipocytesAm J Physiol.(1998 Nov)
      68.^J C Anthony, F Yoshizawa, T G Anthony, T C Vary, L S Jefferson, S R KimballLeucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathwayJ Nutr.(2000 Oct)
      69.^Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SRLeucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathwayJ Nutr.(2000 Oct)
      70.^Drummond MJ, Fry CS, Glynn EL, Dreyer HC, Dhanani S, Timmerman KL, Volpi E, Rasmussen BBRapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesisJ Physiol.(2009 Apr 1)
      72.^Fischer PMCap in hand: targeting eIF4ECell Cycle.(2009 Aug 15)
      73.^Kimball SR, Jefferson LSRegulation of protein synthesis by branched-chain amino acidsCurr Opin Clin Nutr Metab Care.(2001 Jan)
      77.^Vander Haar E, Lee SI, Bandhakavi S, Griffin TJ, Kim DHInsulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40Nat Cell Biol.(2007 Mar)
      78.^Elmadhun NY, Lassaletta AD, Chu LM, Sellke FWMetformin alters the insulin signaling pathway in ischemic cardiac tissue in a swine model of metabolic syndromeJ Thorac Cardiovasc Surg.(2013 Jan)
      80.^Browne GJ, Proud CGRegulation of peptide-chain elongation in mammalian cellsEur J Biochem.(2002 Nov)
      82.^Alvestrand A, Hagenfeldt L, Merli M, Oureshi A, Eriksson LSInfluence of leucine infusion on intracellular amino acids in humansEur J Clin Invest.(1990 Jun)
      83.^Yang J, Chi Y, Burkhardt BR, Guan Y, Wolf BALeucine metabolism in regulation of insulin secretion from pancreatic beta cellsNutr Rev.(2010 May)
      85.^Tipton KD, Elliott TA, Ferrando AA, Aarsland AA, Wolfe RRStimulation of muscle anabolism by resistance exercise and ingestion of leucine plus proteinAppl Physiol Nutr Metab.(2009 Apr)
      86.^Tipton KD, Elliott TA, Cree MG, Aarsland AA, Sanford AP, Wolfe RRStimulation of net muscle protein synthesis by whey protein ingestion before and after exerciseAm J Physiol Endocrinol Metab.(2007 Jan)
      87.^Tipton KD, Rasmussen BB, Miller SL, Wolf SE, Owens-Stovall SK, Petrini BE, Wolfe RRTiming of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exerciseAm J Physiol Endocrinol Metab.(2001 Aug)
      90.^Peters SJ, van Helvoort A, Kegler D, Argilès JM, Luiking YC, Laviano A, van Bergenhenegouwen J, Deutz NE, Haagsman HP, Gorselink M, van Norren KDose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic miceOncol Rep.(2011 Jul)
      92.^Nicastro H, Artioli GG, Costa Ados S, Solis MY, da Luz CR, Blachier F, Lancha AH JrAn overview of the therapeutic effects of leucine supplementation on skeletal muscle under atrophic conditionsAmino Acids.(2011 Feb)
      93.^Fujita S, Volpi EAmino acids and muscle loss with agingJ Nutr.(2006 Jan)
      96.^Rieu I, Sornet C, Bayle G, Prugnaud J, Pouyet C, Balage M, Papet I, Grizard J, Dardevet DLeucine-supplemented meal feeding for ten days beneficially affects postprandial muscle protein synthesis in old ratsJ Nutr.(2003 Apr)
      98.^Kalogeropoulou D, Lafave L, Schweim K, Gannon MC, Nuttall FQLeucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucoseMetabolism.(2008 Dec)
      99.^Bruckbauer A, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JSSynergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and miceNutr Metab (Lond).(2012 Aug 22)
      101.^Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L, Moinard CCitrulline modulates muscle protein metabolism in old malnourished ratsAm J Physiol Endocrinol Metab.(2006 Sep)
      102.^Faure C, Raynaud-Simon A, Ferry A, Daugé V, Cynober L, Aussel C, Moinard CLeucine and citrulline modulate muscle function in malnourished aged ratsAmino Acids.(2012 Apr)
      104.^Cynober L, de Bandt JP, Moinard CLeucine and citrulline: two major regulators of protein turnoverWorld Rev Nutr Diet.(2013)
      106.^Rougé C, Des Robert C, Robins A, Le Bacquer O, Volteau C, De La Cochetière MF, Darmaun DManipulation of citrulline availability in humansAm J Physiol Gastrointest Liver Physiol.(2007 Nov)
      107.^Elango R, Chapman K, Rafii M, Ball RO, Pencharz PBDetermination of the tolerable upper intake level of leucine in acute dietary studies in young menAm J Clin Nutr.(2012 Oct)