Use of Branched-Chain Amino Acids As a Potential Treatment for Improving Nutrition-Related Outcomes in Advanced Chronic Liver Disease

Overview

Journal Nutrients

Date 2023 Oct 14

PMID 37836474

Authors

Santo Colosimo

Simona Bertoli

Francesca Saffioti

Affiliations

Soon will be listed here.

Abstract

Advanced chronic liver disease (ACLD) represents a complex and multifactorial clinical entity characterized by liver dysfunction and associated complications. In recent years, the significance of nutritional status in ACLD prognosis has gained considerable attention. This review article delves into the multifactorial pathogenesis of malnutrition in ACLD and its profound consequences for health outcomes. We explore the clinical implications of secondary sarcopenia in ACLD and highlight the critical relevance of frailty in both decompensated and compensated ACLD. A specific focus of this review revolves around branched-chain amino acids (BCAAs) and their pivotal role in managing liver disease. We dissect the intricate relationship between low Fischer's ratio and BCAA metabolism in ACLD, shedding light on the molecular mechanisms involved. Furthermore, we critically evaluate the existing evidence regarding the effects of BCAA supplementation on outcomes in ACLD patients, examining their potential to ameliorate the nutritional deficiencies and associated complications in this population.

Citing Articles

Hepatocellular carcinoma recurrence: Predictors and management.

Abdelhamed W, El-Kassas M Liver Res. 2025; 7(4):321-332.

PMID: 39958776 PMC: 11791921. DOI: 10.1016/j.livres.2023.11.004.

Intravenous branched-chain amino acid administration for the acute treatment of hepatic encephalopathy: a systematic review and meta-analysis.

Yokobori S, Yatabe T, Kondo Y, Ajimi Y, Araki M, Chihara N J Intensive Care. 2025; 13(1):2.

PMID: 39780295 PMC: 11716518. DOI: 10.1186/s40560-024-00771-x.

Biomarkers of Frailty in Patients with Advanced Chronic Liver Disease Undergoing a Multifactorial Intervention Consisting of Home Exercise, Branched-Chain Amino Acids, and Probiotics.

Laghi L, Ortiz M, Rossi G, Roman E, Mengucci C, Canto E Biomolecules. 2024; 14(11).

PMID: 39595586 PMC: 11592179. DOI: 10.3390/biom14111410.

Home exercise, branched-chain amino acids, and probiotics improve frailty in cirrhosis: A randomized clinical trial.

Roman E, Kaur N, Sanchez E, Poca M, Padros J, Nadal M Hepatol Commun. 2024; 8(5).

PMID: 38701490 PMC: 11073778. DOI: 10.1097/HC9.0000000000000443.

References

Dejong C, van de Poll M, Soeters P, Jalan R, Olde Damink S . Aromatic amino acid metabolism during liver failure. J Nutr. 2007; 137(6 Suppl 1):1579S-1585S. DOI: 10.1093/jn/137.6.1579S. View

Yatsuhashi H, Ohnishi Y, Nakayama S, Iwase H, Nakamura T, Imawari M . Anti-hypoalbuminemic effect of branched-chain amino acid granules in patients with liver cirrhosis is independent of dietary energy and protein intake. Hepatol Res. 2011; 41(11):1027-35. DOI: 10.1111/j.1872-034X.2011.00864.x. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Pelletier V, Marks L, Wagner D, Hoerr R, Young V . Branched-chain amino acid interactions with reference to amino acid requirements in adult men: leucine metabolism at different valine and isoleucine intakes. Am J Clin Nutr. 1991; 54(2):402-7. DOI: 10.1093/ajcn/54.2.402. View

Nishiguchi S, Habu D . Effect of oral supplementation with branched-chain amino acid granules in the early stage of cirrhosis. Hepatol Res. 2004; 30S:36-41. DOI: 10.1016/j.hepres.2004.08.009. View

Chin S, Shepherd R, Thomas B, Cleghorn G, Patrick M, Wilcox J . Nutritional support in children with end-stage liver disease: a randomized crossover trial of a branched-chain amino acid supplement. Am J Clin Nutr. 1992; 56(1):158-63. DOI: 10.1093/ajcn/56.1.158. View

Tajiri K, Shimizu Y . Branched-chain amino acids in liver diseases. Transl Gastroenterol Hepatol. 2018; 3:47. PMC: 6088198. DOI: 10.21037/tgh.2018.07.06. View

Siramolpiwat S, Kiattikunrat K, Soontararatpong R, Pornthisarn B, Vilaichone R, Chonprasertsuk S . Frailty as tested by the Liver Frailty Index is associated with decompensation and unplanned hospitalization in patients with compensated cirrhosis. Scand J Gastroenterol. 2021; 56(10):1210-1219. DOI: 10.1080/00365521.2021.1957497. View

Marchesini G, Dioguardi F, Bianchi G, Zoli M, Bellati G, Roffi L . Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. The Italian Multicenter Study Group. J Hepatol. 1990; 11(1):92-101. DOI: 10.1016/0168-8278(90)90278-y. View

10.

Dioguardi F, Brigatti M, DellOca M, Ferrario E, Abbiati R . Effects of chronic oral branched-chain amino acid supplementation in a subpopulation of cirrhotics. Clin Physiol Biochem. 1990; 8(2):101-7. View

11.

Nishikawa H, Shiraki M, Hiramatsu A, Moriya K, Hino K, Nishiguchi S . Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res. 2016; 46(10):951-63. DOI: 10.1111/hepr.12774. View

12.

Gluud L, Dam G, Les I, Marchesini G, Borre M, Aagaard N . Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2017; 5:CD001939. PMC: 6481897. DOI: 10.1002/14651858.CD001939.pub4. View

13.

Hidaka H, Nakazawa T, Kutsukake S, Yamazaki Y, Aoki I, Nakano S . The efficacy of nocturnal administration of branched-chain amino acid granules to improve quality of life in patients with cirrhosis. J Gastroenterol. 2012; 48(2):269-76. DOI: 10.1007/s00535-012-0632-x. View

14.

Cruz-Jentoft A, Landi F, Schneider S, Zuniga C, Arai H, Boirie Y . Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014; 43(6):748-59. PMC: 4204661. DOI: 10.1093/ageing/afu115. View

15.

Lai J, Rahimi R, Verna E, Kappus M, Dunn M, McAdams-DeMarco M . Frailty Associated With Waitlist Mortality Independent of Ascites and Hepatic Encephalopathy in a Multicenter Study. Gastroenterology. 2019; 156(6):1675-1682. PMC: 6475483. DOI: 10.1053/j.gastro.2019.01.028. View

16.

Harima Y, Yamasaki T, Hamabe S, Saeki I, Okita K, Terai S . Effect of a late evening snack using branched-chain amino acid-enriched nutrients in patients undergoing hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. Hepatol Res. 2010; 40(6):574-84. DOI: 10.1111/j.1872-034X.2010.00665.x. View

17.

Kawaguchi T, Izumi N, Charlton M, Sata M . Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology. 2011; 54(3):1063-70. DOI: 10.1002/hep.24412. View

18.

Ruiz-Margain A, Macias-Rodriguez R, Rios-Torres S, Roman-Calleja B, Mendez-Guerrero O, Rodriguez-Cordova P . Effect of a high-protein, high-fiber diet plus supplementation with branched-chain amino acids on the nutritional status of patients with cirrhosis. Rev Gastroenterol Mex (Engl Ed). 2017; 83(1):9-15. DOI: 10.1016/j.rgmx.2017.02.005. View

19.

Park J, Tak W, Park S, Kweon Y, Chung W, Jang B . Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study. Nutrients. 2020; 12(5). PMC: 7284598. DOI: 10.3390/nu12051429. View

20.

Kakazu E, Kanno N, Ueno Y, Shimosegawa T . Extracellular branched-chain amino acids, especially valine, regulate maturation and function of monocyte-derived dendritic cells. J Immunol. 2007; 179(10):7137-46. DOI: 10.4049/jimmunol.179.10.7137. View