Last Updated: August 17 2022

Isoleucine is one of the three branched chain amino acids and appears to promote glucose consumption and uptake. Isoleucine may have roles as an anti-catabolic agent (without promoting synthesis) similar to HMB.

Isoleucine is most often used for


Isoleucine is one of the three branched chain amino acids alongside both leucine and valine. Relative to the other two BCAAs, isoleucine is intermediate for its ability to induce muscle protein synthesis (stronger than valine, but much weaker than leucine) but is able to significantly increase glucose uptake and the usage of glucose during exercise. Isoleucine does not promote glycogen synthesis, however.

Via a PI3K/aPKC dependent mechanism (which is notable since this is neither mediated by the more common AMPK mechanism seen with supplements like berberine nor muscle contraction-mediated uptake) isoleucine can increase glucose uptake into a muscle cell. Leucine also appears to have this ability, but due to leucine stimulating a protein known as S6K (required for protein synthesis) leucine reduces its own efficacy by hindering insulin-stimulated uptake. In other words, while isoleucine and leucine both stimulate glucose uptake leucine then shoots itself in the foot and hinders itself while isoleucine just acts in a predictable and linear manner.

Although extensive human testing has not been conducted yet, isoleucine can be seen as the BCAA which mediates glucose uptake (into a cell) and breakdown (into energy) to a larger degree than other amino acids and may serve a role as a hypoglycemic (in diabetics) or as a performance enhancer (if taken preworkout in a carbohydrate replete state).

Dosage information

Isoleucine, practically speaking, is likely only a good supplement to purchase when wanting to increase glucose uptake; it is outperformed by leucine for inducing muscle protein synthesis and outperformed by HMB for reducing muscle protein breakdown, yet outperforms both of those agents and valine in increasing glucose uptake into skeletal muscle.

As efficacy has been noted with 0.3-0.45g/kg in rats (the latter being the maximal dose, increasing beyond that does nothing more due to no further absorption) a recommended dosage range for isoleucine per se is 48-72mg/kg (for a 150lb person, 3.3-4.9g).

Isoleucine can be found in branched chain amino acids (in which case, the ratio listed on the label should be investigated and the BCAAs dosed accordingly) and in food products. As isoleucine from food products is also bioactive, supplemental doses of isoleucine taken with meals can be lower (ie. if eating a meal with 50g protein that contains 4g isoleucine already, then a 10.8g dose is no longer needed and 6.8g will suffice).

3.^Doi M, Yamaoka I, Fukunaga T, Nakayama MIsoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubesBiochem Biophys Res Commun.(2003 Dec 26)
5.^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)
7.^Lynch CJ, Fox HL, Vary TC, Jefferson LS, Kimball SRRegulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytesJ Cell Biochem.(2000 Mar)
8.^Bernard JR, Liao YH, Hara D, Ding Z, Chen CY, Nelson JL, Ivy JLAn amino acid mixture improves glucose tolerance and insulin signaling in Sprague-Dawley ratsAm J Physiol Endocrinol Metab.(2011 Apr)
10.^Nishitani S, Takehana K, Fujitani S, Sonaka IBranched-chain amino acids improve glucose metabolism in rats with liver cirrhosisAm J Physiol Gastrointest Liver Physiol.(2005 Jun)
11.^Watson RT, Pessin JEBridging the GAP between insulin signaling and GLUT4 translocationTrends Biochem Sci.(2006 Apr)
12.^Kleinert M, Liao YH, Nelson JL, Bernard JR, Wang W, Ivy JLAn amino acid mixture enhances insulin-stimulated glucose uptake in isolated rat epitrochlearis muscleJ Appl Physiol.(2011 Jul)
13.^Wang B, Kammer LM, Ding Z, Lassiter DG, Hwang J, Nelson JL, Ivy JLAmino acid mixture acutely improves the glucose tolerance of healthy overweight adultsNutr Res.(2012 Jan)
16.^Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JMHuman beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosisCell.(1997 Feb 21)
17.^Harder J, Bartels J, Christophers E, Schröder JMA peptide antibiotic from human skinNature.(1997 Jun 26)
18.^Ganz T, Lehrer RIDefensinsPharmacol Ther.(1995 May)
19.^Raqib R, Sarker P, Bergman P, Ara G, Lindh M, Sack DA, Nasirul Islam KM, Gudmundsson GH, Andersson J, Agerberth BImproved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibioticProc Natl Acad Sci U S A.(2006 Jun 13)
20.^Sherman H, Chapnik N, Froy OAlbumin and amino acids upregulate the expression of human beta-defensin 1Mol Immunol.(2006 Apr)
21.^Fehlbaum P, Rao M, Zasloff M, Anderson GMAn essential amino acid induces epithelial beta -defensin expressionProc Natl Acad Sci U S A.(2000 Nov 7)
22.^Alam NH, Raqib R, Ashraf H, Qadri F, Ahmed S, Zasloff M, Agerberth B, Salam MA, Gyr N, Meier RL-isoleucine-supplemented oral rehydration solution in the treatment of acute diarrhoea in children: a randomized controlled trialJ Health Popul Nutr.(2011 Jun)
23.^Buller CL, Loberg RD, Fan MH, Zhu Q, Park JL, Vesely E, Inoki K, Guan KL, Brosius FC 3rdA GSK-3/TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expressionAm J Physiol Cell Physiol.(2008 Sep)