Isoleucine

Last Updated: October 13, 2023

Isoleucine is one of the three branched-chain amino acids (BCAAs). It is an essential amino acid. Isoleucine is required for muscle protein synthesis, and it may help to reduce post-exercise muscle soreness and markers of muscle damage when taken as part of a BCAA supplement. However, whether isoleucine holds any special merit as a supplement on its own is unclear.

dosageDosage

Isoleucine is most often used for

What is isoleucine?

Isoleucine is one of the three branched-chain amino acids (BCAAs), along with valine and leucine. As an essential amino acid, isoleucine needs to be consumed regularly and can be found naturally in dietary proteins like meat, fish, soy, and dairy.[4][5] Isoleucine serves as a building block for proteins, but it’s also thought to function as a signaling molecule in the body, involved in the regulation of protein, glucose, and lipid metabolism; glucose transport; and immune function.[6]

What are isoleucine’s main benefits?

Isoleucine is essential for muscle growth and may play a role in muscle recovery, similar to other essential amino acid, but it’s unclear whether supplementing isoleucine alone above the RDA provides any particular benefits.

Isoleucine is necessary for the process of muscle protein synthesis, and BCAAs in general are thought to be particularly important for stimulating this process while also minimizing protein breakdown.[7][8] However, compared to leucine, isoleucine does not stimulate muscle protein synthesis to a significant degree, and ultimately, research suggests that optimal muscle protein synthesis is achieved when all nine essential amino acid are present.[9][10] In terms of muscle recovery, when isoleucine is taken as part of a BCAA supplemen,t it seems to reduce post-exercise muscle soreness and markers of muscle damage, but may not impact the recovery of muscle performance.[11][12][13]

Animal studies suggest that isoleucine enhances the uptake of glucose by muscle cells and increases the breakdown of glucose into energy.[2] While theoretically this might be beneficial for exercise performance, studies providing isoleucine as part of a BCAA supplement have not consistently found a positive effect on performance, and isoleucine has generally not been studied alone.[13]

What are isoleucine’s main drawbacks?

Isoleucine is usually well-tolerated, but some people may experience gastrointestinal upset (e.g., nausea, diarrhea).[14] Importantly, these side effects have been observed when isoleucine was taken as part of a BCAA supplement; the potential side effects of isoleucine when supplemented alone are undetermined.

Observational studies have found that increased levels of isoleucine in the blood are associated with certain health conditions, including insulin resistance,[15] type 2 diabetes,[16][15] cardiovascular disease,[17][18] and obesity.[19][20] Further research is needed to determine whether these elevated levels of isoleucine are a cause or an effect of these conditions.

How does isoleucine work?

Isoleucine is an amino acid used by the body during protein synthesis, which is required for muscle growth and recovery. In terms of glucose metabolism and transport, research in rodents suggests that isoleucine reduces blood glucose levels by enhancing the uptake of glucose by skeletal muscle cells, increasing the overall breakdown of glucose into energy, and reducing the amount of glucose produced by the liver (hepatic gluconeogenesis).[2][3]

Dosage information

The recommended daily allowance (RDA) of isoleucine established by the Institute of Medicine is 19 mg of isoleucine per kilogram of bodyweight (mg/kg) daily. This is the average amount of isoleucine that meets the nutritional requirements of most people.[1]

Isoleucine can be supplemented individually, but it is more commonly taken as part of a BCAA or complete protein supplement (e.g., whey protein, soy protein). There is currently no strong evidence to support the use of isoleucine as a supplement alone and no well-established dosing.

In rat studies, dosages of 0.3–0.45 mg/kg were effective for reducing blood glucose and increasing muscle cell glucose uptake.[2][3] This could be extrapolated to a human dose of 48–72 mg/kg (for a 150 lb person, 3.3–4.9 g), but these beneficial effects have not yet been clearly established in clinical trials.

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Update History
2023-10-13 00:30:02

New studies added to FAQs

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We added a bit more information to our FAQs on this page, largely related to isoleucine's relationship with glucose control.

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2023-09-12 17:02:58

Standard FAQ and database update

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We searched for new studies on isoleucine, analyzed them, and added their information to our FAQs and database.

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References
  1. ^Institute of MedicineDietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino AcidsThe National Academies Press.(2005)
  2. ^Masako Doi, Ippei Yamaoka, Mitsuo Nakayama, Kunio Sugahara, Fumiaki YoshizawaHypoglycemic effect of isoleucine involves increased muscle glucose uptake and whole body glucose oxidation and decreased hepatic gluconeogenesisAm J Physiol Endocrinol Metab.(2007 Jun)
  3. ^Masako Doi, Ippei Yamaoka, Tetsuya Fukunaga, Mitsuo NakayamaIsoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubesBiochem Biophys Res Commun.(2003 Dec 26)
  4. ^Górska-Warsewicz H, Laskowski W, Kulykovets O, Kudlińska-Chylak A, Czeczotko M, Rejman KFood Products as Sources of Protein and Amino Acids-The Case of Poland.Nutrients.(2018-Dec-13)
  5. ^Kudełka W, Kowalska M, Popis MQuality of Soybean Products in Terms of Essential Amino Acids Composition.Molecules.(2021-Aug-21)
  6. ^Nie C, He T, Zhang W, Zhang G, Ma XBranched Chain Amino Acids: Beyond Nutrition Metabolism.Int J Mol Sci.(2018-Mar-23)
  7. ^Kerksick CM, Wilborn CD, Roberts MD, Smith-Ryan A, Kleiner SM, Jäger R, Collins R, Cooke M, Davis JN, Galvan E, Greenwood M, Lowery LM, Wildman R, Antonio J, Kreider RBISSN exercise & sports nutrition review update: research & recommendationsJ Int Soc Sports Nutr.(2018 Aug 1)
  8. ^Louard RJ, Barrett EJ, Gelfand RAOvernight branched-chain amino acid infusion causes sustained suppression of muscle proteolysis.Metabolism.(1995-Apr)
  9. ^Moberg M, Apró W, Ekblom B, van Hall G, Holmberg HC, Blomstrand EActivation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise.Am J Physiol Cell Physiol.(2016-Jun-01)
  10. ^Jackman SR, Witard OC, Philp A, Wallis GA, Baar K, Tipton KDBranched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein Synthesis following Resistance Exercise in HumansFront Physiol.(2017 Jun 7)
  11. ^Kenji Doma, Utkarsh Singh, Daniel Boullosa, Jonathan Douglas ConnorThe effect of branched-chain amino acid on muscle damage markers and performance following strenuous exercise: a systematic review and meta-analysisAppl Physiol Nutr Metab.(2021 Nov)
  12. ^Chutimon Khemtong, Chia-Hua Kuo, Chih-Yen Chen, Salvador J Jaime, Giancarlo CondelloDoes Branched-Chain Amino Acids (BCAAs) Supplementation Attenuate Muscle Damage Markers and Soreness after Resistance Exercise in Trained Males? A Meta-Analysis of Randomized Controlled TrialsNutrients.(2021 May 31)
  13. ^Martinho DV, Nobari H, Faria A, Field A, Duarte D, Sarmento HOral Branched-Chain Amino Acids Supplementation in Athletes: A Systematic Review.Nutrients.(2022-Sep-27)
  14. ^Gluud LL, Dam G, Les I, Córdoba J, Marchesini G, Borre M, Aagaard NK, Vilstrup HBranched-chain amino acids for people with hepatic encephalopathy.Cochrane Database Syst Rev.(2015-Sep-17)
  15. ^Long J, Yang Z, Wang L, Han Y, Peng C, Yan C, Yan DMetabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis.BMC Endocr Disord.(2020-Nov-23)
  16. ^Ramzan I, Ardavani A, Vanweert F, Mellett A, Atherton PJ, Idris IThe Association between Circulating Branched Chain Amino Acids and the Temporal Risk of Developing Type 2 Diabetes Mellitus: A Systematic Review & Meta-Analysis.Nutrients.(2022-Oct-20)
  17. ^Flores-Guerrero JL, Groothof D, Connelly MA, Otvos JD, Bakker SJL, Dullaart RPFConcentration of Branched-Chain Amino Acids Is a Strong Risk Marker for Incident Hypertension.Hypertension.(2019-Dec)
  18. ^Wang Y, Huang K, Liu F, Lu X, Huang J, Gu DAssociation of circulating branched-chain amino acids with risk of cardiovascular disease: A systematic review and meta-analysis.Atherosclerosis.(2022-Jun)
  19. ^Ho JE, Larson MG, Ghorbani A, Cheng S, Chen MH, Keyes M, Rhee EP, Clish CB, Vasan RS, Gerszten RE, Wang TJMetabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes.PLoS One.(2016)
  20. ^N Geidenstam, M Al-Majdoub, M Ekman, P Spégel, M RidderstråleMetabolite profiling of obese individuals before and after a one year weight loss programInt J Obes (Lond).(2017 Sep)
  21. ^Ikehara O, Kawasaki N, Maezono K, Komatsu M, Konishi AAcute and chronic treatment of L-isoleucine ameliorates glucose metabolism in glucose-intolerant and diabetic mice.Biol Pharm Bull.(2008-Mar)
  22. ^Newmire DE, Rivas E, Deemer SE, Willoughby DS, Ben-Ezra VThe Impact of a Large Bolus Dose of l-leucine and l-isoleucine on Enteroendocrine and Pancreatic Hormones, and Glycemia in Healthy, Inactive Adults.Nutrients.(2019-Nov-04)
  23. ^Elovaris RA, Hajishafiee M, Ullrich SS, Fitzgerald PCE, Lange K, Horowitz M, Feinle-Bisset CIntragastric administration of leucine and isoleucine does not reduce the glycaemic response to, or slow gastric emptying of, a carbohydrate-containing drink in type 2 diabetes.Diabetes Res Clin Pract.(2021-Jan)
  24. ^Elovaris RA, Bitarafan V, Agah S, Ullrich SS, Lange K, Horowitz M, Feinle-Bisset CComparative Effects of the Branched-Chain Amino Acids, Leucine, Isoleucine and Valine, on Gastric Emptying, Plasma Glucose, C-Peptide and Glucagon in Healthy Men.Nutrients.(2021-May-11)
  25. ^Cholsoon Jang, Sungwhan F Oh, Shogo Wada, Glenn C Rowe, Laura Liu, Mun Chun Chan, James Rhee, Atsushi Hoshino, Boa Kim, Ayon Ibrahim, Luisa G Baca, Esl Kim, Chandra C Ghosh, Samir M Parikh, Aihua Jiang, Qingwei Chu, Daniel E Forman, Stewart H Lecker, Saikumari Krishnaiah, Joshua D Rabinowitz, Aalim M Weljie, Joseph A Baur, Dennis L Kasper, Zoltan AranyA branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistanceNat Med.(2016 Apr)
  26. ^Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, Jang C, Kasza I, Nikodemova M, Wakai MH, Tomasiewicz JL, Yang SE, Miller BR, Pak HH, Brinkman JA, Rojas JM, Quinn WJ, Cheng EP, Konon EN, Haider LR, Finke M, Sonsalla M, Alexander CM, Rabinowitz JD, Baur JA, Malecki KC, Lamming DWThe adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine.Cell Metab.(2021-May-04)
  27. ^Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, Lamming DWRestoration of metabolic health by decreased consumption of branched-chain amino acids.J Physiol.(2018-Feb-15)
  28. ^Qin LQ, Xun P, Bujnowski D, Daviglus ML, Van Horn L, Stamler J, He K,Higher branched-chain amino acid intake is associated with a lower prevalence of being overweight or obese in middle-aged East Asian and Western adults.J Nutr.(2011-Feb)
  29. ^Li YC, Li Y, Liu LY, Chen Y, Zi TQ, Du SS, Jiang YS, Feng RN, Sun CHThe Ratio of Dietary Branched-Chain Amino Acids is Associated with a Lower Prevalence of Obesity in Young Northern Chinese Adults: An Internet-Based Cross-Sectional Study.Nutrients.(2015-Nov-18)
  30. ^Ramzan I, Taylor M, Phillips B, Wilkinson D, Smith K, Hession K, Idris I, Atherton PA Novel Dietary Intervention Reduces Circulatory Branched-Chain Amino Acids by 50%: A Pilot Study of Relevance for Obesity and Diabetes.Nutrients.(2020-Dec-30)
  31. ^Karusheva Y, Koessler T, Strassburger K, Markgraf D, Mastrototaro L, Jelenik T, Simon MC, Pesta D, Zaharia OP, Bódis K, Bärenz F, Schmoll D, Wolkersdorfer M, Tura A, Pacini G, Burkart V, Müssig K, Szendroedi J, Roden MShort-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial.Am J Clin Nutr.(2019-Nov-01)