My Cart

Close
 

HMB AND HICA SUPPLEMENTS DON’T IMPROVE MUSCLE GROWTH OR STRENGTH!

Brian Turner

Posted on December 18 2018

By Steve Blechman

 

NEW STUDY!

β-hydroxy-β-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that is produced in skeletal muscle. α-hydroxyisocaproic acid (α-HICA) is also a metabolite of the amino acid leucine. It is often sold as a purported muscle-building supplement. Animal research has shown that HMB can increase body mass in animals. As a supplement for humans, HMB is marketed as an anti-catabolic nutrient that decreases protein breakdown. A dose of 3 grams of HMB daily has been recommended to augment resistance training/induced changes in body composition and performance. A most recent study published in Medicine & Science Sports & Exercise January 2019 showed that the leucine metabolite, HMB and HICA, as supplements don’t improve muscle growth or strength in young adult men.

Purpose We aimed to conduct a double-blind randomized controlled pragmatic trial to evaluate the effects of off-the-shelf leucine metabolite supplements of α-HICA, HMB-FA, and HMB-Ca on resistance training-induced changes in muscle thickness and performance.

Methods Forty men were randomly assigned to receive α-HICA (n = 10, fat-free mass [FFM] = 62.0 ± 7.1 kg), HMB-FA (n = 11, FFM = 62.7 ± 10.5 kg), HMB-Ca (n = 9, FFM = 65.6 ± 10.1 kg), or placebo (PLA; n = 10, FFM = 64.2 ± 5.7 kg). The training program consisted of whole-body, thrice- weekly resistance training for 8 wk (seven exercises per session, three to four sets per session, at 70%-80% one repetition maximum). Skeletal muscle thickness by ultrasound, performance measures, and blood measures (creatine kinase, insulin-like growth factor 1, growth hormone, cortisol, and total testosterone) were evaluated at baseline and at the end of weeks 4 and 8.

Results Time-dependent changes were observed for muscle thickness (P < 0.001), one repetition maximum bench press and squat (P < 0.001), Wingate peak power (P = 0.02), countermovement jump height (P = 0.03), power (P = 0.006), creatine kinase, insulin-like growth factor-1, growth hormone, and cortisol (all P < 0.001). No significant between-group or time-group interactions were observed.

Conclusions No leucine metabolite resulted in any ergogenic effects on any outcome variable. Supplementation with leucine metabolites— α-HICA, HMB-FA, or HMB-Ca— is not a supplementation strategy that improves muscle growth and strength development in young adult men.”

WHY LEUCINE IS STILL KING

Leucine is an essential amino acid that serves as a building block for muscle protein synthesis. Leucine is a powerful anabolic trigger— it’s the most potent branched-chain amino acid (BCAA) and a key activator of the mTOR pathway that is critical for muscle protein synthesis that promotes muscle growth. Leucine has many growth benefits: preventing muscle loss, increasing insulin sensitivity, enhancing fat metabolism and enhancing recovery.

Leucine, not branched-chain amino acids, is the most important chemical that turns on the mTOR pathway, so it is likely that consuming leucine after exercise would be more effective (and cheaper) than consuming BCAAs. The addition of isoleucine and valine may hinder the benefits of leucine due to competition for transport into muscle cells. The BCAAs share the same active transport system into cells and muscle cells. Indeed, isoleucine and valine have been shown to inhibit absorption of leucine.

Robert R. Wolfe, noted amino acid researcher, said in the Journal of the International Society of Sports Nutrition (2017) that “BCAAs also compete with other amino acids for transport, including phenylalanine, and this competition could affect the intramuscular availability of other EAAs. As a result of competition for transporters, it is possible that leucine alone, for example, could have a transitory stimulatory effect on muscle protein synthesis where the BCAAs fail to elicit such response.”

Studies indicate increases in muscle protein synthesis are dependent on leucine concentration! Leucine stimulates the anabolic effects of muscle protein by itself. Ingestion of leucine alone can independently activate mTOR and muscle protein synthesis. A Japanese study published on October 18, 2018 in the journal Nutrients found that taking leucine supplements alone may be better for muscle protein synthesis and more anabolic than leucine from food! Japanese researchers found that blood levels of leucine were higher from pure, free leucine taken alone compared to the same amount of leucine in a meal. Increase in muscle protein synthesis is dependent on leucine concentration. Research clearly has shown that leucine stimulates the anabolic effect of muscle protein on its own (Wilkinson et al., J Physiol, 2013). The Nutrients study showed that, “based on these findings, it is presumed that compared to the intake of protein alone or free amino acids alone, the intake of dietary protein from mixed meals may result in a lower maximum plasma leucine concentration. However, no study to date has investigated the changes in amino acid concentrations after the ingestion of mixed meals in comparison to those after the intake of a similar amount of free amino acids.”

In a randomized crossover study, 10 healthy, young Japanese men underwent tests under different conditions: consuming 2 grams of leucine alone; a mixed meal with 2.15 grams of leucine without any additional leucine supplementation; 2 grams of leucine right after a meal; and the final serving consisted of 2 grams of leucine, 180 minutes after a meal.

The study concluded that “based on the aforementioned discussions, the intake of free leucine alone markedly increased the plasma leucine concentration. However, the increase in leucine concentration after the intake of a mixed meal containing the same amount of leucine was significantly less than that of free leucine intake alone. Moreover, when free leucine was ingested after a mixed meal with the purpose of increasing the plasma leucine concentration, the maximum plasma concentration was attenuated when it was ingested immediately after the mixed meal, despite the fact that the total leucine content was doubled. These results suggest that when free amino acids ingested with the purpose of increasing plasma amino acid concentrations, the timing in relation to the mixed meal intake needs to be considered.”

For best results to use as an anabolic trigger, take 5 grams of leucine (on an empty stomach) 30 minutes before a post-workout meal, or protein shake. A meta-analysis (Nutrition, 2017) that combined the results of seven studies showed that BCAA supplements are best taken after exercise, not before or during exercise (intra-workout.)

Increase in muscle protein synthesis is dependant on leucine concentration. Research has shown that leucine stimulates the anabolic effect of protein synthesis on its own. (Wilkinson et al, J. Physiol, 2013.) When leucine is taken on an on an empty stomach, it has a powerful anabolic switch that turns on protein synthesis. By taking pure leucine on an empty stomach, you will get a better spike in blood levels than if you take leucine with food, because food can slow leucine’s absorption. The addition of isoleucine and valine may hinder the benefits of leucine due to competition for transport into muscle cells. When leucine is taken on an empty stomach, it’s a powerful metabolic switch that turns on protein synthesis. Leucine increases mTOR activity for several hours after training. When leucine is taken after resistance exercise and before a post-workout, protein-containing meal rich in essential amino acids, it triggers greater protein synthesis for improved recovery and greater gains.

In conclusion, the research shows that leucine is king and a powerful anabolic trigger and enhances protein synthesis and can promote muscle growth and recovery. Also, leucine supplementation can improve mitochondrial biogenesis and function, increase insulin sensitivity and may also enhance fat loss and improve lean body mass.

References:

Leucine Metabolites Do Not Enhance Training-induced Performance or Muscle Thickness.

Teixeira Filipe J, Matias Catarina N, Monteiro Cristina P, Valamatos Maria J, Reis Joana F, Tavares Francisco, Batista Ana, Domingos Christophe, Alves Francisco, Sardinha Luís B, Phillips Stuart M. Medicine & Science in Sports & Exercise. Vol. 51, Issue 1, Jan 1, 2019

Effects of combined β-hydroxy-β-methylbutyrate (HMB) and whey protein ingestion on symptoms of eccentric exercise-induced muscle damage. Shirato M, Tsuchiya Y, Sato T, Hamano S, Gushiken T, Kimura N & Ochi E. (2016). Journal of the International Society of Sports Nutrition, 13, 7. doi:10.1186/s12970-016-0119-x

Exercise-Induced Muscle Damage Is Not Attenuated by β-Hydroxy-β-Methylbutyrate and α-Ketoisocaproic Acid Supplementation. Nunan D, Howatson G et al. Journal of Strength and Conditioning Research: February 2010 

Equivalent Hypertrophy and Strength Gains in β-Hydroxy-β-Methylbutyrate- or Leucine-supplemented Men. Jakubowski Josephine S, Wong Phillips, Stuart M et al. Medicine & Science in Sports & Exercise: January 2019

Nutrients 2018, 10(10), 1543; https://doi.org/10.3390/nu10101543 Effect of Mixed Meal and Leucine Intake on Plasma Amino Acid Concentrations in Young Men. N Yoshii at al.

Rahimi MH, Shab-Bidar S et al. Branched-chain amino acid supplementation and exercise-induced muscle damage in exercise recovery: A meta-analysis of randomized clinical trials. Nutrition 2017.

ISSN exercise & sports nutrition review update: research & recommendations. Chad M Kerksick, Colin D, Wilborn Michael D.

Roberts, et al. Journal of the International Society of Sports Nutrition 2018 15:38 https://doi.org/10.1186/s12970-018-0242-y 1 June 2018

Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? Robert R Wolfe. Journal of the International Society of Sports Nutrition201714:30 https://doi.org/10.1186/s12970-017-0184-9

Szmelcman S, Guggenheim K. Interference between leucine, isoleucine and valine during intestinal absorption. Biochemical Journal 1966;100(1):7-11.

Wilkinson DJ et al. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrateonhumanskeletalmuscleproteinmetabolism. J Physiol 2013, 591, 2911-2923.

Cummings NE, Williams EM Kasza, I Konon et al. (2018), Restoration of metabolic health by decreased consumption of branched‐chain amino acids. J Physiol, 596: 623-645. doi:10.1113/JP275075

Duke University. "Diabetes researchers find switch for fatty liver disease: Carbs, fats and protein: One molecule to rule them all?" ScienceDaily. ScienceDaily, 17 May 2018. www.sciencedaily.com/releases/2018/05/180517113847.htm

PJ White, RW McGarrah, PA Grimsrud, S Tso, W Yang, JM Haldeman, C Newgard et al. The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase. Cell Metabolism, 2018; DOI: 10.1016/j.cmet.2018.04.015

NutraIngredients-USA.com, December 17, 2017. Nathan Gray. Could dropping specific amino acids from diet be key to weight loss?

CB Newgard J An, JR Bain et al. A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance Cell Metab. 2009 April; 9(4): 311-326. doi:10.1016/j.cmet.2009.02.002

Zheng Y, Li Y, Qi Q et al. Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes. Int J Epidemiol 2016; 45: 1482-92.

Isanejad M, LaCroix AZ, Thomson CA et al. Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women’s Health Initiative. Br J Nutr 2017; 117:1523-30.

Newgard CB, An J, Bain JR et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009; 9: 311-26

Tremblay F, Krebs M, Dombrowski L et al. Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability. Diabetes 2005; 54: 2674-84.

Lee CC, Watkins SM, Lorenzo C et al. Branched-chain amino acids and insulin metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care 2016; 39: 582-8.

Yoon M-S. The emerging role of branched-chain amino acids in insulin resistance and metabolism. Forum Nutr 2016; 8: 405-17.

Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care 2006; 29:1130-9.

Jang C, Oh SF, et al A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat Med 22, 421-426

Sara B Seidelmann, Brian Claggett, Susan Cheng, Mir Henglin, Amil Shah, Lyn M Steffen, Aaron R Folsom, Eric B Rimm, Walter C Willett, Scott D Solomon, Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis, The Lancet Public Health, 2018, ISSN 2468-2667, https://doi.org/10.1016/S2468-2667(18)30135-X.

Zhaoping Li, Professor of Medicine, UCLA, US National Library of Medicine www. ClinicalTrials.gov Identifier: NCT02684565 Last Update Posted: February 12, 2018 https://clinicaltrials.gov/ct2/show/NCT02684565

Lotta LA, Scott RA, Sharp SJ, Burgess S, Luan J, et al. (2016) Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis. PLOS Medicine 13(11): e1002179. https://doi.org/10.1371/journal.pmed.1002179

Avogaro A and Bier D.M. (1989) Contribution of 3-hydroxyisobutyrate to the measurement of 3-hydroxybutyrate in human plasma: comparison of enzymatic and gas-liquid chromatography-mass spectrometry assays in normal and in diabetic subjects. J Lipid Res 30, 1811-1817

Giesbertz P, Padberg I, et al. (2015) Metabolite profiling in plasma and tissues of ob/ob and db/db mice identifies novel markers of obesity and type 2 diabetes. Diabetologia 58, 2133-2143.

Insulin Resistance, And What May Contribute To It by Lila Abassi on March 14, 2016. American Council on Science & Health https://www.acsh.org/news/2016/03/14/branched-chain-amino-metabolite-a-culprit-in-insulin-resistance

Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion–Induced Insulin Resistance Lydia-Ann L.S. Harris, Gordon I Smith, Bruce W Patterson, Raja S Ramaswamy et al. Diabetes 2017;66:1871-1878 https://doi.org/10.2337/db16-1475

Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes Mardinoglu, Adil et al. EBioMedicine, Volume 27, 151-155, Jan 2018.

Ulrika Andersson-Hall, Carolina Gustavsson, Anders Pedersen, Daniel Malmodin, Louise Joelsson, and Agneta Holmäng, “Higher Concentrations of BCAAs and 3-HIB Are Associated with Insulin Resistance in the Transition from Gestational Diabetes to Type 2 Diabetes,” Journal of Diabetes Research, vol. 2018, Article ID 4207067, 12 pages, 2018. https://doi.org/10.1155/2018/4207067.

Macotela Y Emanuelli, B Bang, AM et al. (2011) Dietary leucine – an environmental modifier of insulin resistance acting on multiple levels of metabolism. PLoS One 6, e21187.

Branched Chain Amino Acids: Beyond Nutrition Metabolism. Cunxi Nie, Ting He, Wenju Zhang, Guolong Zhang, Xi Ma. Int J Mol Sci. 2018 Apr; 19(4): 954. Published online 2018 Mar 23. doi: 10.3390/ijms19040954

Increasing Dietary Leucine Intake Reduces Diet-Induced Obesity and Improves Glucose and Cholesterol Metabolism in Mice via Multimechanisms. Y Zhang, K Guo, RE LeBlanc, D Loh, GJ Schwartz, Y Yu. Diabetes Jun 2007, 56 (6) 1647-1654; DOI: 10.2337/db07-0123

Dietary Intakes and Circulating Concentrations of Branched-Chain Amino Acids in Relation to Incident Type 2 Diabetes Risk Among High-Risk Women with a History of Gestational Diabetes Mellitus. Deirdre K Tobias, Clary Clish, Samia Mora, Jun Li, Liming Liang, Frank B Hu, JoAnn E Manson, Cuilin Zhang. Clinical Chemistry Aug 2018, 64 (8) 1203-1210; DOI: 10.1373/clinchem.2017.285841

McCormack SE, Shaham O, McCarthy MA, Deik AA, Wang TJ, Gerszten RE, Clish CB, Mootha VK, Grinspoon SK and Fleischman A. (2013), Branched‐chain amino acids and IR in children. Pediatric Obesity, 8: 52-61. doi:10.1111/j.2047-6310.2012.00087.x.

Sina S Ullrich, Penelope CE Fitzgerald, Gudrun Schober, Robert E Steinert, Michael Horowitz, Christine Feinle-Bisset; Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers. The American Journal of Clinical Nutrition, Volume 104, Issue 5, 1 November 2016, Pages 1274-1284, https://doi.org/10.3945/ajcn.116.140640.

Branched-chain and aromatic amino acids, insulin resistance and liver specific ectopic fat storage in overweight to obese subjects. Haufe S et al. Nutrition, Metabolism and Cardiovascular Diseases, Volume 26 , Issue 7, 637-642

Li H, Xu M, Lee J, He C & Xie Z. (2012). Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. American Journal of Physiology - Endocrinology and Metabolism, 303(10), E1234-E1244. http://doi.org/10.1152/ajpendo.00198.2012

Chunzi Liang, Benjamin J Curry, Patricia L Brown, and Michael B. Zemel, “Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes,” Journal of Nutrition and Metabolism, vol. 2014, Article ID 239750, 11 pages, 2014. https://doi.org/10.1155/2014/239750.

Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. Binder E, Bermúdez-Silva FJ, André C, Elie M, Romero-Zerbo SY, et al. (2013) Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. PLOS ONE 8(9): e74705. https://doi.org/10.1371/journal.pone.0074705

Activation of the AMPK/Sirt1 pathway by a leucine–metformin combination increases insulin sensitivity in skeletal muscle, and stimulates glucose and lipid metabolism and increases life span in Caenorhabditis elegans. Banerjee, Jheelam et al. Metabolism - Clinical and Experimental, Volume 65, Issue 11, 1679-1691

Jiao J, Han S-F, Zhang W, Xu J-Y, Tong X, Yin X-B, Qin L-Q. (2016). Chronic leucine supplementation improves lipid metabolism in C57BL/6J mice fed with a high-fat/cholesterol diet. Food & Nutrition Research, 60, 10.3402/fnr.v60.31304. http://doi.org/10.3402/fnr.v60.31304

Published: 07 March 2016. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. 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 Arany. Nature Medicine volume 22, pages 421-426 (2016)

D’Antona G, Ragni M, Cardile A, Tedesco L, Dossena M, Bruttini F. et al. (2010). Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab. 12, 362-372. doi: 10.1016/j.cmet.2010.08.016

Szmelcman S, Guggenheim K. Interference between leucine, isoleucine and valine during intestinal absorption. Biochemical Journal. 1966;100(1):7-11.

Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? Robert R. Wolfe Journal of the International Society of Sports Nutrition201714:30 https://doi.org/10.1186/s12970-017-0184-9

Antagonistic effects of leucine and glutamine on the mTOR pathway in myogenic C2C12 cells. Amino Acids, 2008, Volume 35, Number 1, Page 147 L. Deldicque, C. Sanchez Canedo, S. Horman.

Protein Recommendations for Weight Loss in Elite Athletes: A Focus on Body Composition and Performance. Amy Hector, Stuart M. Phillips Int J Sport Nutr Exerc Metab. 2017

Leucine, Not Total Protein, Content of a Supplement Is the Primary Determinant of Muscle Protein Anabolic Responses in Healthy Older Women, The Journal of Nutrition, nxy091, June 13, 2018

Branched-chain amino acid supplementation and exercise-induced muscle damage in exercise recovery: A meta-analysis of randomized clinical trials. Rahimi MH, Shab-Bidar S, Mollahosseini M, Djafarian K. Nutrition. 2017

Jiao J, Han SF, Zhang W, Xu JY, Tong X, Yin XB, Yuan LX, Qin LQ. (2016). Chronic leucine supplementation improves lipid metabolism in C57BL/6J mice fed with a high-fat/cholesterol diet. Food & nutrition research, 60, 31304. doi:10.3402/fnr.v60.31304

Macotela Y, Emanuelli B, Ba˚ng AM, Espinoza DO, Boucher J, Beebe K, et al. Dietary leucine an environmental modifier of insulin resistance acting on multiple levels of metabolism. PLoS One 2011; 6: e21187.

Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 2007; 56: 164754.

Khan M, Joseph F. Adipose tissue and adipokines: the association with and application of adipokines in obesity. Scientifica (Cairo) 2014; 2014: 328592

Zemel MB, Bruckbauer A. Effects of a leucine and pyridoxine containing nutraceutical on fat oxidation, and oxidative and inflammatory stress in overweight and obese subjects. Nutrients 2012; 4: 52941

Ricoult SJ, Manning BD. The multifaceted role of mTORC1 in the control of lipid metabolism. EMBO Rep 2013; 14: 24251

Freudenberg A, Petzke KJ, Klaus S. Comparison of highprotein diets and leucine supplementation in the prevention of metabolic syndrome and related disorders in mice. J Nutr Biochem 2012; 3: 152430.

Vaughan RA, Garcia-Smith R, Gannon NP, Bisoffi M, Trujillo KA, Conn CA. Leucine treatment enhances oxidative capacity through complete carbohydrate oxidation and increased mitochondrial density in skeletal muscle cells. Amino Acids 2013; 45: 90111.

Zhang Y et al (2007) Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 56(6):1647–1654

Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis. Okekunle AP, Zhang M, Wang Z et al. Acta Diabetol (2018). https://doi.org/10.1007/s00592-018-1243-7

Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. Binder E, Bermúdez-Silva FJ, André C, Elie M, Romero-Zerbo SY, et al. (2013) Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. PLOS ONE 8(9): e74705. https://doi.org/10.1371/journal.pone.0074705

Binder E, Bermúdez‐Silva FJ, Elie M, Leste‐Lasserre T, Belluomo I, Clark S, Duchampt A, Mithieux G and Cota D. (2014), Leucine supplementation modulates fuel substrates utilization and glucose metabolism in previously obese mice. Obesity, 22: 713-720. doi:10.1002/oby.20578

Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. Li H, Xu M, Lee J, He C & Xie Z. (2012). American journal of physiology. Endocrinology and metabolism, 303(10), E1234-44.

(2015). Reviewing the Effects of L-Leucine Supplementation in the Regulation of Food Intake, Energy Balance, and Glucose Homeostasis. Pedroso JA, Zampieri TT & Donato J. Nutrients, 7(5), 3914-37. https://dx.doi.org/10.3390%2Fnu7053914

Caoileann H Murphy, Nelson I Saddler, Michaela C Devries, Chris McGlory, Steven K Baker, Stuart M Phillips; Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study, The American Journal of Clinical Nutrition, Volume 104, Issue 6, 1 December 2016, Pages 1594-1606, https://doi.org/10.3945/ajcn.116.136424

Yadao DR, MacKenzie S and Bergdahl A. (2018), Reducing branched‐chain amino acid intake to reverse metabolic complications in obesity and type 2 diabetes. J Physiol, 596: 3455-3456. doi:10.1113/JP276274