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25.04.2022 | Original Article

Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia

verfasst von: Srikant Mohta, Abhinav Anand, Sanchit Sharma, Sumaira Qamar, Samagra Agarwal, Deepak Gunjan, Namrata Singh, Kumble Seetarama Madhusudhan, Ravindra Mohan Pandey, Anoop Saraya

Erschienen in: Hepatology International | Ausgabe 3/2022

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Abstract

Background

The role of branched-chain amino acids (BCAA) in improving muscle mass in cirrhosis is presently debatable.

Aims

To evaluate the role of BCAA in improving muscle mass in a double-blind randomized placebo-controlled trial in patients with cirrhosis having sarcopenia.

Methods

Consecutive patients with cirrhosis with Child–Pugh score < 10 and sarcopenia were randomized to receive either 12 g/day of BCAA orally or a placebo (1:1) for 6 months in addition to a home-based exercise program (30 min/day), dietary counselling and standard medical therapy. Sarcopenia was defined according to gender-specific axial skeletal muscle index (SMI) cut-offs. The primary endpoint was a change in muscle mass based on CT scan (SMI) after 6 months of supplementation.

Results

Sixty patients [mean age 41.6 ± 9.9 years; males (66.6%) of predominantly viral (40%) and alcohol-related (31.7%) cirrhosis] were randomized. Baseline clinical and demographic characters were similar except MELD score (10.2 ± 2.8 vs. 12.2 ± 3.5, p = 0.02) and calorie intake (1838.1 kcal ± 631.5 vs. 2217.5 kcal ± 707.3, p = 0.03), both being higher in the placebo arm. After adjusting for both baseline confounders, baseline SMI and protein intake, the change in SMI at 6 months was similar in both groups [mean adjusted difference (MAD) + 0.84, CI − 2.9; + 1.2, p = 0.42] by intention-to-treat analysis. The secondary outcomes including change in handgrip strength (p = 0.65), 6-m gait speed (p = 0.20), 6-min walk distance (p = 0.39) were similar in both arms. Four patients had minor adverse events in each arm.

Conclusion

Addition of BCAA to exercise, dietary counselling and standard medical therapy did not improve muscle mass in patients with cirrhosis having sarcopenia. (CTRI/2019/05/019269).

Trial registration number

CTRI/2019/05/019269 (Clinical Trials Registry of India).

Nur mit Berechtigung zugänglich

Dasarathy S. Consilience in sarcopenia of cirrhosis. J Cachexia Sarcopenia Muscle 2012;3(4):225–237. https://doi.org/10.1007/s13539-012-0069-3CrossRefPubMedPubMedCentral

Krell RW, Kaul DR, Martin AR, et al. Association between sarcopenia and the risk of serious infection among adults undergoing liver transplantation. Liver Transpl 2013;19(12):1396–1402. https://doi.org/10.1002/lt.23752CrossRefPubMed

Montano-Loza AJ, Meza-Junco J, Prado CMM, et al. Muscle wasting is associated with mortality in patients. Clin Gastroenterol Hepatol 2012;10(2):166–173. https://doi.org/10.1016/j.cgh.2011.08.028 (173.e1)CrossRefPubMed

Carey EJ, Lai JC, Wang CW, et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl 2017;23(5):625–633. https://doi.org/10.1002/lt.24750CrossRefPubMedPubMedCentral

Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol 2016;65(6):1232–1244. https://doi.org/10.1016/j.jhep.2016.07.040CrossRefPubMedPubMedCentral

Naseer M, Turse EP, Syed A, Dailey FE, Zatreh M, Tahan V. Interventions to improve sarcopenia in cirrhosis: a systematic review. World J Clin Cases 2019;7(2):156–170. https://doi.org/10.12998/wjcc.v7.i2.156CrossRefPubMedPubMedCentral

Saunders J, Brian A, Wright M, Stroud M. Malnutrition and nutrition support in patients with liver disease. Frontline Gastroenterol 2010;1(2):105–111. https://doi.org/10.1136/fg.2009.000414CrossRefPubMedPubMedCentral

Holecek M. Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy. Nutrition 2015;31(1):14–20. https://doi.org/10.1016/j.nut.2014.03.016CrossRefPubMed

Qiu J, Tsien C, Thapalaya S, et al. Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab 2012;303(8):E983-993. https://doi.org/10.1152/ajpendo.00183.2012CrossRefPubMedPubMedCentral

10.

Pere MC, Baudelin A, Briggs K, Teng C, Gilbert M. Hepatic amino acid metabolism during hyperinsulinemia and hyperaminoacidemia in conscious rabbit during late pregnancy. Metabolism 1994;43(9):1079–1085. https://doi.org/10.1016/0026-0495(94)90048-5CrossRefPubMed

11.

Nishitani S, Ijichi C, Takehana K, Fujitani S, Sonaka I. Pharmacological activities of branched-chain amino acids: specificity of tissue and signal transduction. Biochem Biophys Res Commun 2004;313(2):387–389. https://doi.org/10.1016/j.bbrc.2003.11.023CrossRefPubMed

12.

Dam G, Ott P, Aagaard NK, Vilstrup H. Branched-chain amino acids and muscle ammonia detoxification in cirrhosis. Metab Brain Dis 2013;28(2):217–220. https://doi.org/10.1007/s11011-013-9377-3CrossRefPubMed

13.

Kitajima Y, Takahashi H, Akiyama T, et al. Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis. J Gastroenterol 2018;53(3):427–437. https://doi.org/10.1007/s00535-017-1370-xCrossRefPubMed

14.

Nishida Y, Ide Y, Okada M, et al. Effects of home-based exercise and branched-chain amino acid supplementation on aerobic capacity and glycemic control in patients with cirrhosis. Hepatol Res 2017;47(3):E193–E200. https://doi.org/10.1111/hepr.12748CrossRefPubMed

15.

Marchesini G, Bianchi G, Merli M, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology 2003;124(7):1792–1801CrossRefPubMed

16.

Nakaya Y, Okita K, Suzuki K, et al. BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition 2007;23(2):113–120. https://doi.org/10.1016/j.nut.2006.10.008CrossRefPubMed

17.

Kikuchi Y, Hiroshima Y, Matsuo K, et al. A randomized clinical trial of preoperative administration of branched-chain amino acids to prevent postoperative ascites in patients with liver resection for hepatocellular carcinoma. Ann Surg Oncol 2016;23(11):3727–3735. https://doi.org/10.1245/s10434-016-5348-3CrossRefPubMed

18.

Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008;371(9615):838–851. https://doi.org/10.1016/S0140-6736(08)60383-9CrossRefPubMedPubMedCentral

19.

Sarin SK, Kumar A, Almeida JA, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2008;3(1):269–282. https://doi.org/10.1007/s12072-008-9106-xCrossRefPubMedPubMedCentral

20.

Fedorov A, Beichel R, Kalpathy-Cramer J, et al. 3D Slicer as an image computing platform for the quantitative imaging network. Magn Reson Imaging 2012;30(9):1323–1341. https://doi.org/10.1016/j.mri.2012.05.001CrossRefPubMedPubMedCentral

21.

Portal D, Hofstetter L, Eshed I, et al. L3 skeletal muscle index (L3SMI) is a surrogate marker of sarcopenia and frailty in non-small cell lung cancer patients. Cancer Manag Res 2019;11:2579–2588. https://doi.org/10.2147/CMAR.S195869CrossRefPubMedPubMedCentral

22.

Sousa-Santos AR, Amaral TF. Differences in handgrip strength protocols to identify sarcopenia and frailty—a systematic review. BMC Geriatr 2017;17(1):238. https://doi.org/10.1186/s12877-017-0625-yCrossRefPubMedPubMedCentral

23.

Statement ATS. Guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166(1):111–117. https://doi.org/10.1164/ajrccm.166.1.at1102CrossRef

24.

Younossi ZM, Guyatt G, Kiwi M, Boparai N, King D. Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease. Gut 1999;45(2):295–300. https://doi.org/10.1136/gut.45.2.295CrossRefPubMedPubMedCentral

25.

Benjamin J, Mani K, Saraya A, Joshi YK. Translation and validation of the Hindi version of chronic liver disease questionnaire (CLDQ) for the assessment of health related quality of life in patient with chronic liver disease in India. Trop Gastroenterol 2017;37(2):112–122. https://doi.org/10.7869/tg.335CrossRef

26.

Román E, Torrades MT, Nadal MJ, et al. Randomized pilot study: effects of an exercise programme and leucine supplementation in patients with cirrhosis. Dig Dis Sci 2014;59(8):1966–1975. https://doi.org/10.1007/s10620-014-3086-6CrossRefPubMed

27.

Aamann L, Dam G, Borre M, et al. Resistance training increases muscle strength and muscle size in patients with liver cirrhosis. Clin Gastroenterol Hepatol 2020;18(5):1179-1187.e6. https://doi.org/10.1016/j.cgh.2019.07.058CrossRefPubMed

28.

Singh Tejavath A, Mathur A, Nathiya D, et al. Impact of branched chain amino acid on muscle mass, muscle strength, physical performance, combined survival, and maintenance of liver function changes in laboratory and prognostic markers on sarcopenic patients with liver cirrhosis (BCAAS study): a randomized clinical trial. Front Nutr 2021;8:619. https://doi.org/10.3389/fnut.2021.715795CrossRef

29.

Benjamin J, Shasthry V, Kaal CR, et al. Characterization of body composition and definition of sarcopenia in patients with alcoholic cirrhosis: a computed tomography based study. Liver Int 2017;37(11):1668–1674. https://doi.org/10.1111/liv.13509CrossRefPubMed

30.

Mukherjee PS, Vishnubhatla S, Amarapurkar DN, et al. Etiology and mode of presentation of chronic liver diseases in India: a multi centric study. PLoS ONE 2017;12(10): e0187033. https://doi.org/10.1371/journal.pone.0187033CrossRefPubMedPubMedCentral

31.

Davuluri G, Krokowski D, Guan BJ, et al. Metabolic adaptation of skeletal muscle to hyperammonemia drives the beneficial effects of l-leucine in cirrhosis. J Hepatol 2016;65(5):929–937. https://doi.org/10.1016/j.jhep.2016.06.004CrossRefPubMedPubMedCentral

32.

Tsien C, Davuluri G, Singh D, et al. Metabolic and molecular responses to leucine-enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis. Hepatology 2015;61(6):2018–2029. https://doi.org/10.1002/hep.27717CrossRefPubMed

33.

Les I, Doval E, García-Martínez R, et al. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study. Am J Gastroenterol 2011;106(6):1081–1088. https://doi.org/10.1038/ajg.2011.9CrossRefPubMed

34.

Hiraoka A, Michitaka K, Kiguchi D, et al. Efficacy of branched-chain amino acid supplementation and walking exercise for preventing sarcopenia in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2017;29(12):1416–1423. https://doi.org/10.1097/MEG.0000000000000986CrossRefPubMed

35.

Hiraoka A, Kiguchi D, Ninomiya T, et al. Can l-carnitine supplementation and exercise improve muscle complications in patients with liver cirrhosis who receive branched-chain amino acid supplementation? Eur J Gastroenterol Hepatol 2019;31(7):878–884. https://doi.org/10.1097/MEG.0000000000001368CrossRefPubMed

36.

Hernández-Conde M, Llop E, Gómez-Pimpollo L, et al. Adding branched-chain amino acids to an enhanced standard-of-care treatment improves muscle mass of cirrhotic patients with sarcopenia: a placebo-controlled trial. Am J Gastroenterol ACG 2021. https://doi.org/10.14309/ajg.0000000000001301 (latest articles)CrossRef

37.

Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? J Int Soc Sports Nutr 2017;14:30. https://doi.org/10.1186/s12970-017-0184-9CrossRefPubMedPubMedCentral

38.

Louard RJ, Barrett EJ, Gelfand RA. Effect of infused branched-chain amino acids on muscle and whole-body amino acid metabolism in man. Clin Sci (Lond) 1990;79(5):457–466. https://doi.org/10.1042/cs0790457CrossRef

39.

Louard RJ, Barrett EJ, Gelfand RA. Overnight branched-chain amino acid infusion causes sustained suppression of muscle proteolysis. Metabolism 1995;44(4):424–429. https://doi.org/10.1016/0026-0495(95)90047-0CrossRefPubMed

40.

Hamaguchi Y, Kaido T, Okumura S, et al. Proposal for new diagnostic criteria for low skeletal muscle mass based on computed tomography imaging in Asian adults. Nutrition 2016;32(11–12):1200–1205. https://doi.org/10.1016/j.nut.2016.04.003CrossRefPubMed

41.

Lai JC, Dodge JL, Kappus MR, et al. A multicenter pilot randomized clinical trial of a home-based exercise program for patients with cirrhosis: the strength training intervention (STRIVE). Am J Gastroenterol ACG 2021. https://doi.org/10.14309/ajg.0000000000001113 (publish ahead of print)CrossRef

Titel: Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia
verfasst von: Srikant Mohta
Abhinav Anand
Sanchit Sharma
Sumaira Qamar
Samagra Agarwal
Deepak Gunjan
Namrata Singh
Kumble Seetarama Madhusudhan
Ravindra Mohan Pandey
Anoop Saraya
Publikationsdatum: 25.04.2022
Verlag: Springer India
Erschienen in: Hepatology International / Ausgabe 3/2022
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI: https://doi.org/10.1007/s12072-022-10334-7

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Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia