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

Arun Singh Tejavath, Amit Mathur, Deepak Nathiya, Pratima Singh, Preeti Raj, Supriya Suman, Payal Ramakant Mundada, Sheikh Atif, Ramesh Roop Rai, Balvir Singh Tomar, Arun Singh Tejavath, Amit Mathur, Deepak Nathiya, Pratima Singh, Preeti Raj, Supriya Suman, Payal Ramakant Mundada, Sheikh Atif, Ramesh Roop Rai, Balvir Singh Tomar

Abstract

Background: This study aimed to investigate the long-term effects of branched-chain amino acids (BCAAs) supplementations on the parameters associated with improved prognosis in sarcopenic patients with liver cirrhosis (LC) and evaluate its impact on cirrhotic-related events. Methods: A 24-week, single-center, randomized, open-label, controlled, two cohort parallel-group intervention study was carried out by comparing the efficacy of BCAAs against lactoalbumin (L-ALB) on 106 sarcopenic patients with LC. The BCAA (intervention) group was treated with 7.2 g BCAA per dose, whereas the L-ALB group was treated with 6.3 g of L-ALB. The primary outcome was to assess the effect of BCAA on the parameters of sarcopenia, such as muscle mass, muscle strength, and physical performance. The secondary outcomes were to study the combined survival and maintenance of liver function changes in laboratory and prognostic markers over the duration of 6 months. Results: The treatment with BCAA leads to the significant improvement in sarcopenic parameters, such as muscle strength, muscle function, and muscle mass. The total cirrhotic-related complications and cumulative event-free survival occurred fewer in the BCAA group than in the L-ALB group. In addition, prognostic markers improved significantly in the study. Conclusion: The current study demonstrated that long-term BCAAs supplementation improved sarcopenia and prognostic markers in patients with advanced LC.

Keywords: albumin; branched-chain amino acid; liver cirrhosis; quality of life; sarcopenia.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Singh Tejavath, Mathur, Nathiya, Singh, Raj, Suman, Mundada, Atif, Rai and Tomar.

Figures

Figure 1
Figure 1
Schematic study plan in consideration of the patients enrolled in the study.
Figure 2
Figure 2
(A) Changes in Hand-grip strength in BCAA and L-ALB group over a period of 24 weeks. (B) Changes in muscle function in BCAA and L-ALB group over a period of 24 weeks. Changes in muscle mass based on the different variables; (C) Total abdominal muscles area (TAMA) circumference; (D) Fat-fold triceps; (E) Mid-upper arm circumference; (F) Mid-arm muscle circumference in BCAA and L-ALB group over 24 weeks. Statistically significant at p < 0.05.
Figure 3
Figure 3
Kaplan Meier analysis of cumulative event-free survival in patients supplemented with BCAA and L-ALB group over 24 weeks. Events were considered death (any reason) and deterioration to exclusion criteria. Statistically significant at p < 0.05.
Figure 4
Figure 4
Mean changes in Albumin concentration (A), Child Turcotte Pugh score (B), MELD score (C), and Total Bilirubin level (D) in subjects supplemented with BCAA (black scale) or L-ALB (grayscale) over 24 weeks. MELD, Model for End-stage Liver Disease. Statistically significant at p < 0.05.

References

    1. Merli M, Riggio O, Dally L. Does malnutrition affect survival in cirrhosis? Hepatology. (1996) 23:1041–6. 10.1002/hep.510230516
    1. Peng S, Plank LD, McCall JL, Gillanders LK, McIlroy K, Gane EJ. Body composition, muscle function, and energy expenditure in patients with liver cirrhosis: a comprehensive study. Am J Clin Nutr. (2007) 85:1257–66. 10.1093/ajcn/85.5.1257
    1. Hanai T, Shiraki M, Nishimura K, Ohnishi S, Imai K, Suetsugu A, et al. . Sarcopenia impairs prognosis of patients with liver cirrhosis. Nutrition. (2015) 31:193–9. 10.1016/j.nut.2014.07.005
    1. Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, et al. . The epidemiology of cirrhosis in the United States a population-based study. J Clin Gastroenterol. (2015) 49:690–6. 10.1097/MCG.0000000000000208
    1. Montano-Loza AJ, Meza-Junco J, Baracos VE, Prado CMM, Ma M, Meeberg G, et al. . Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation. Liver Transplant. (2014) 20:640–8. 10.1002/lt.23863
    1. Tsien CD, Mccullough AJ, Dasarathy S. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis. J Gastroenterol Hepatol. (2012) 27:430–41. 10.1111/j.1440-1746.2011.06951.x
    1. Tessari P. Protein metabolism in liver cirrhosis: from albumin to muscle myofibrils. Curr Opin Clin Nutr Metab Care. (2003) 6:79–85. 10.1097/00075197-200301000-00012
    1. Dasarathy S. Consilience in sarcopenia of cirrhosis. J Cachexia Sarcopenia Muscle. (2012) 3:225–37. 10.1007/s13539-012-0069-3
    1. Owen OE, Trapp VE, Reichard GA, Mozzoli MA, Moctezuma J, Paul P, et al. . Nature and quantity of fuels consumed in patients with alcoholic cirrhosis. J Clin Invest. (1983) 72:1821–32. 10.1172/JCI111142
    1. Shimomura Y, Yamamoto Y, Bajotto G, Sato J, Murakami T, Shimomura N, et al. . Nutraceutical effects of branched-chain amino acids on skeletal muscle. J Nutr. (2006) 136:529S. 10.1093/jn/136.2.529S
    1. Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, et al. . Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. (2003) 323:8. 10.1016/S0016-5085(03)00323-8
    1. Ray G. Trends of chronic liver disease in a tertiary care referral hospital in Eastern India. Indian J Public Health. (2014) 58:186–94. 10.4103/0019-557X.138630
    1. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. . Sarcopenia: European consensus on definition and diagnosis. Age Ageing. (2010) 39:412–23. 10.1093/ageing/afq034
    1. Plauth M, Merli M, Kondrup J, Weimann A, Ferenci P, Muller MJ, et al. . guidelines for nutrition in liver disease and transplantation. Clin Nutr. (1997) 16:43–55. 10.1016/S0261-5614(97)80022-2
    1. Stewart A, Marfell-Jones M, Olds T, de Ridder JH. International Society for the Advancement of Kinantropometry. Int. Stand. Anthr. Assessment. Aust. Low. Hutt New Zeal. Int. Soc. Adv. Kinanthropometry. (2001) 1:57–72.
    1. Frisancho AR. New standards of weight and body composition by frame size and height for assessment of nutritional status of adults and the elderly. Am J Clin Nutr. (1984) 40:808–19. 10.1093/ajcn/40.4.808
    1. Fryar CD, Gu Q, Ogden CL. Anthropometric reference data for children and adults: United States, 2007-2010. Vital Health Stat. (2012) 252:1–48.
    1. Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, et al. . review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing. (2011) 40:423–9. 10.1093/ageing/afr051
    1. Horowitz B, Tollin R, Cassidy G. Grip strength. Phys Occup Ther Geriatr. (1997) 15:53–64. 10.1300/J148v15n01_04
    1. Bruyère O, Beaudart C, Reginster JY, Buckinx F, Schoene D, Hirani V, et al. . Assessment of muscle mass, muscle strength and physical performance in clinical practice: an international survey. Eur Geriatr Med. (2016) 7:243–6. 10.1016/j.eurger.2015.12.009
    1. Cooper C, Fielding R, Visser M, Van Loon LJ, Rolland Y, Orwoll E, et al. . Tools in the assessment of sarcopenia. Calcif Tissue Int. (2013) 93:201–10. 10.1007/s00223-013-9757-z
    1. Tsoris A, Marlar CA. Use of the Child Pugh Score in Liver Disease. (2019). Available online at: (accessed April 29, 2021).
    1. Ko CH, Wu SJ, Wang ST, Chang YF, Chang CS, Kuan TS, et al. . Effects of enriched branched-chain amino acid supplementation on sarcopenia. Aging. (2020) 12:15091–103. 10.18632/aging.103576
    1. Bohé J, Low A, Wolfe RR, Rennie MJ. Human muscle protein synthesis is modulated by extracellular, not intramuscular amino acid availability: a dose-response study. J Physiol. (2003) 552:315–24. 10.1113/jphysiol.2003.050674
    1. Pasiakos SM, Mcclung JP. Supplemental dietary leucine and the skeletal muscle anabolic response to essential amino acids. Nutr Rev. (2011) 69:550–7. 10.1111/j.1753-4887.2011.00420.x
    1. Bianchi G, Marzocchi R, Agostini F, Marchesini G. Update on nutritional supplementation with branched-chain amino acids. Curr Opin Clin Nutr Metab Care. (2005) 8:83–7. 10.1097/00075197-200501000-00013
    1. Alberino F, Gatta A, Amodio P, Merkel C, Di Pascoli L, Boffo G, et al. . Nutrition and survival in patients with liver cirrhosis. Nutrition. (2001) 17:445–50. 10.1016/S0899-9007(01)00521-4
    1. Fanelli FR, Cangiano C, Capocaccia L, Cascino A, Ceci F, Muscaritoli M, et al. . Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences. Gut. 27:111–5. 10.1136/gut.27.suppl_1.111
    1. Charlton M. Branched-chain amino acid enriched supplements as therapy for liver disease. J Nutr. (2006) 136:295S−8S. 10.1093/jn/136.1.295S
    1. Blonde-Cynober F, Aussel C, Cynober L. Abnormalities in branched-chain amino acid metabolism in cirrhosis: influence of hormonal and nutritional factors and directions for future research. Clin Nutr. (1999) 18:5–13. 10.1016/S0261-5614(99)80043-0
    1. Lochs H, Dejong C, Hammarqvist F, Hebuterne X, Leon-Sanz M, Schütz T, et al. . ESPEN guidelines on enteral nutrition: gastroenterology. Clin Nutr. (2006) 25:260–74. 10.1016/j.clnu.2006.01.007
    1. Park JG, Tak WY, Park SY, Kweon YO, Jang SY, Lee YR, et al. . Effects of branched-chain amino acids (BCAAs) on the progression of advanced liver disease: a Korean nationwide, multicenter, retrospective, observational, cohort study. Med. (2017) 96:6580. 10.1097/MD.0000000000006580
    1. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. . A model to predict survival in patients with end-stage liver disease. Hepatology. (2001) 33:464–70. 10.1053/jhep.2001.22172
    1. Wiesner R, Edwards E, Freeman R, Harper A, Kim R, Kamath P, et al. . Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. (2003) 124:91–6. 10.1053/gast.2003.50016
    1. Park JG, Tak WY, Park SY, Kweon YO, Chung WJ, Jang BK, et al. . 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) 12:51429. 10.3390/nu12051429
    1. Kalman DR, Saltzman JR. Nutrition status predicts survival in cirrhosis. Nutr Rev. (1996) 54:217–9. 10.1111/j.1753-4887.1996.tb03937.x
    1. Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem. (1998) 273:14484–94. 10.1074/jbc.273.23.14484
    1. Habu D, Nishiguchi S, Nakatani S, Lee C, Enomoto M, Tamori A, et al. . Comparison of the effect of BCAA granules on between decompensated and compensated cirrhosis. Hepatogastroenterology. (2009) 56:1719–23.
    1. 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 intakehepr. Hepatol Res. (2011) 41:1027–35. 10.1111/j.1872-034X.2011.00864.x
    1. Conn HO. A peek at the child-turcotte classification. Hepatology. (1981) 1:673–6. 10.1002/hep.1840010617
    1. Albers I, Hartmann H, Bircher J, Creutzfeldt W. Superiority of the child-pugh classification to quantitative liver function tests for assessing prognosis of liver cirrhosis. Scand J Gastroenterol. (1989) 24:269–76. 10.3109/00365528909093045
    1. Merkel C, Morabito A, Sacerdoti D, Bolognesi M, Angeli P, Gatta A. Updating prognosis of cirrhosis by Cox's regression model using Child-Pugh score and aminopyrine breath test as time-dependent covariates. Ital J Gastroenterol Hepatol. (1998) 30:276–82.
    1. Proud CG. Regulation of mammalian translation factors by nutrients. Eur J Biochem. (2002) 269:5338–49. 10.1046/j.1432-1033.2002.03292.x
    1. Marchesini G, Dioguardi FS, Bianchi GP, Zoli M, Bellati G, Roffi L, et al. . Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. J Hepatol. (1990) 11:92–101. 10.1016/0168-8278(90)90278-Y

Source: PubMed

3
Iratkozz fel