Author(s): Prabhat Varshney, Prem Saini

Email(s): ,

DOI: 10.5958/0974-360X.2020.00622.8   

Address: Prabhat Varshney1*, Prem Saini2*
1Ph.D. Scholar, School of Pharmacy, Lingaya’s Vidyapeeth, Faridabad, Haryana, India.
2Head, School of Pharmacy, Lingaya’s Vidyapeeth, Faridabad, Haryana, India.
*Corresponding Author

Published In:   Volume - 13,      Issue - 7,     Year - 2020

Due to nutrition distortions and energy metabolism, protein energy malnutrition (PEM) is triggered in liver cirrhosis (LC). Since PEM is directly related to the prognosis of LC, it has been postulated that supplementation of Branched Chain Amino Acids (BCAAs) which comprised of the amino acids valine, leucine and isoleucine is helpful in LC. Decreased BCAAs and increased Aromatic Amino Acids (AAAs) are typical abnormalities in the blood of individuals with liver cirrhosis, which play a function in the pathogenesis of hepatic encephalopathy and muscle loss. As the concentration of AAAs increased, it was hypothesized that the influx of AAAs into the brain increased, resulting in an imbalance of the neurotransmitter synthesis, particularly serotonin and noradrenaline. It may cause an aggregation of 'false' neurotransmitters such as octopamine, which may in effect be responsible for Hepatic Encephalopathy associative cognitive impairment. HE is a reversible disordered brain function condition that arises in people with progressive liver failure. BCAAs treatment significantly raises the BCAAs/AAAs ratio and reduces the grade of hepatic encephalopathy. Since the nutritional treatment focused on the administration of BCAAs, it resulted in an improvement in the clinical condition, which also led to an improvement in quality of live (QOL).

Cite this article:
Prabhat Varshney, Prem Saini. Role of Branched Chain Amino Acids supplementation on quality of life in liver cirrhosis patients. Research J. Pharm. and Tech. 2020; 13(7): 3516-3519. doi: 10.5958/0974-360X.2020.00622.8

Prabhat Varshney, Prem Saini. Role of Branched Chain Amino Acids supplementation on quality of life in liver cirrhosis patients. Research J. Pharm. and Tech. 2020; 13(7): 3516-3519. doi: 10.5958/0974-360X.2020.00622.8   Available on:

1. Charlton MR. Protein metabolism and liver disease. Baillieres Clin Endocrinol Metab 1996; 10: 617-635.
2. Kawaguchi T, Yamagishi S, Sata M. Branched-chain amino acids and pigment epithelium-derived factor: novel therapeutic agents for hepatitis c virus-associated insulin resistance. Curr Med Chem 2009; 16: 4843-4857. 
3. Lautz HU, Selberg O, Korber J, et al. Forms of malnutrition in patients with liver cirrhosis. Clin Invest 1992; 70:178–86. 
4. Crawford DHG, Shepherd RW, Halliday JW, et al. Body composition in nonalcoholic cirrhosis: the effect of disease etiology and severity on nutritional compartments. Gastroenterology 1994; 106:1611–7.
5. Kondrup J, Muller MJ. Energy and protein requirements of patients with chronic liver disease. J Hepatol 1997; 27: 239–47. 
6. Alberino F, Gatta A, Amodio P, et al. Nutrition and survival in patients with liver cirrhosis. Nutrition 2001; 17: 445–50. 
7. Tajika M, Kato M, Mohri H, et al. Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition 2002; 18: 229–34. 
8. Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophagealvarices. Br J Surg 1973; 60:646 – 649. 
9. Christensen E, Schlichting P, Fauerholdt L, et al. Prognostic value of Child-Turcotte criteria in medically treated cirrhosis. Hepatology 1984; 4:430–435. 
10. Merkel C, Bolognesi M, Finucci GF, et al. Indocyanine green intrinsic hepatic clearance as a prognostic index of survival in patients with cirrhosis. J Hepatol 1989; 9: 16–22. 
11. Cabre E, Gonzalez-Huix F, Abad-LaCruz A, et al. Effects of total enteral nutrition on short-term outcome of severely malnourished cirrhosis. Gastroenterology 1990; 98: 715–720. 
12. Mendenhall CL, Tosch T, Weesner RE, et al. VA cooperative study on alcoholic hepatitis II: prognostic significance of protein-calorie malnutrition. Am J Clin Nutr 1986;43:213
13. Christie ML, Sack DM, Pomposelli J et al. Enriched branched-chain amino acid formula versus a casein-based supplement in the treatment of cirrhosis. JPEN J Parenter Enteral Nutr 1985; 9: 671–8.
14. McGhee A, Henderson JM, Millikan WJ Jr et al. Comparison of the effects of Hepatic-Aid and a Casein modular diet on encephalopathy, plasma amino acids, and nitrogen balance in cirrhotic patients. Ann Surg1983; 197:288– 93. 
15. Italian Multicentre Cooperative Project on Nutrition in Liver Cirrhosis. Nutritional status in cirrhosis. J Hepatol 1994; 21: 317–25.
16. 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):1792–1801.
17. Muto Y, Yoshida T. Effect of oral supplementation with branched- chain amino acid granules on improvement of protein nutrition in decompensated liver cirrhosis: a cross-over controlled study. In: Ogoshi S, Okada A, eds. Parenteral and enteral hyper-alimentation. Amsterdam: Excerpta Medica, 1984:280–292. 
18. Muto Y, Yoshida T, Sato S, et al. Effect of oral supplementation with BCAAS-G on the prognosis of liver cirrhosis. JJPEN 1992; 14: 765–775.
19. Kawaguchi T, Izumi N, Charlton MR, Sata M. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology. 2011; 54(3):1063-1070. 
20. Charlton M. Branched-chain amino acid enriched supplements as therapy for liver disease. J Nutr. 2006; 136(suppl 1):295S-298S.
21. Plauth M, Schutz T. Branched-chain amino acids in liver disease: new aspects of long known phenomena. Curr Opin Clin Nutr Metab Care. 2011; 14(1):61-66. 
22. Yoshizawa F. New therapeutic strategy for amino acid medicine: nota- ble functions of branched chain amino acids as biological regulators. J Pharmacol Sci. 2012; 118(2):149-155.
23. Paul HS, Adibi SA. Activation of hepatic branched chain alpha- keto acid dehydrogenase by a skeletal muscle factor. J Biol Chem. 1982; 257(21):12581-12588. 
24. Damuni Z, Merryfield ML, Humphreys JS, Reed LJ. Purification and properties of branched-chain alpha-keto acid dehydrogenase phosphatase from bovine kidney. Proc Natl Acad Sci U S A. 1984; 81(14):4335- 4338. 
25. Holecek M. Three targets of branched-chain amino acid supplementation in the treatment of liver disease. Nutrition. 2010; 26(5):482-490.
26. Marchesini G, Dioguardi FS, Bianchi GP, 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. 
27. Kato M, Miwa Y, Tajika M, et al. Preferential use of branched-chain amino acids as an energy substrate in patients with liver cirrhosis. Intern Med 1998; 37:429–34. 
28. Schuppan, D., and Afdhal, N. H. (2008). Liver cirrhosis. The Lancet, 371(9615), 838–851. doi: 10.1016/s0140-6736(08) 60383-9
29. Schaffner H, Popper H. Capillarization of the sinusoids. Gastroenterology. 1963; 44: 339–42.
30. Fischer JE, Funovics JM, Aguirre A, James JH, Keane JM, Wesdorp RI, et al. The role of plasma amino acids in hepatic encephalopathy. Surgery. 1975; 78:276–90. 
31. Dasarathy S, Hatzoglou M. Hyperammonemia and proteostasis in cirrhosis. Curr Opin Clin Nutr Metab Care. 2018; 21:30–6.
32. Fischer JE, Baldessarini RJ. False neurotransmitters and hepatic failure. Lancet 1971; ii: 75–80. 
33. Fischer JE, Rosen HM, Ebeid AM, et al. The effect of normalization of plasma amino acids on hepatic encephalopathy in man. Surgery 1976; 80: 77–91.
34. A.S.P.E.N. Board of Directors. The clinical guidelines task force: guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients, Liver disease. J Parenter Enter Nutr 2002; 26: 65SA–8SA. 
35. Hayashi M, Ohnishi H, Kawada Y, et al. Augmented utilization of branched-chain amino acids by skeletal muscle in decompensated liver cirrhosis in special relation to ammonia detoxication. Gastroenterol Jpn 1981; 16:64–70. 
36. Yamato M, Muto Y, Yoshida T, et al. Clearance rate of plasma branched-chain amino acids correlates significantly with blood ammonia level in patients with liver cirrhosis. Hepatol Res 1995; 3: 91–6. 
37. Leweling H, Breitkreutz R, Behne F, et al. Hyperammonemia- induced depletion of glutamate and branched-chain amino acids in muscle and plasma. J Hepatol 1996; 25: 756–62.
38. Munro HN, Fernstrom JD, Wurtman RJ. Insulin, plasma amino acid imbalance and hepatic coma. Lancet 1975; I: 724–72. 
39. Kato A. Abnormality in plasma branched chain amino acid in chronic hepatic failure: on its relationship with ammonia and insulin. J Iwate Med Assoc 1984; 36: 565–76 (in Japanese). 
40. Rabbani P, Prasad AS. Plasma ammonia and liver ornithine trans-carbamoylase activity in zinc-deficient rats. Am J Physiol. 1978; 235(2):E203 -E206. 
41. Moriyama M, Matsumura H, Fukushima A, et al. Clinical significance of evaluation of serum zinc concentrations in C-viral chronic liver disease. Dig Dis Sci. 2006; 51(11):1967-1977. 
42. Nagasue N, Kolno H, Chang YC, Nakamura T. Iron, copper and zinc level in serum and cirrhotic liver of patients with and without hepatocellular carcinoma. Oncology. 1989; 46 (5):293-296. 
43. Riggio O, Merli M, Capocaccia L, et al. Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis. Hepatology. 1992; 16(3):785-789. 
44. Aquilio E, Spagnoli R, Riggio D, Seri S. Effects of zinc on hepatic orni- thinetranscarbamylase (OTC) activity. J Trace Elem Electrolytes Health Dis. 1993; 7(4):240-241.
45. Hayashi M, Ikezawa K, Ono A, et al. Evaluation of the effects of combination therapy with branched-chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis. Hepatol Res. 2007; 37(8):615-619. 
46. Takuma Y, Nouso K, Makino Y, Hayashi M, Takahashi H. Clinical trial: oral zinc in hepatic encephalopathy. Aliment Pharmacol Ther. 2010; 32(9):1080-1090. 
47. Ndraha S, Hasan I, Simadibrata M. The effect of L-ornithine L-aspartate and branch chain amino acids on encephalopathy and nutritional status in liver cirrhosis with malnutrition. Acta Med Indones. 2011; 43(1):18-22. 
48. Malaguarnera M, Risino C, Cammalleri L, et al. Branched chain amino acids supplemented with L-acetylcarnitine versus BCAAS treatment in hepatic coma: a randomized and controlled double blind study. Eur J Gastroenterol Hepatol. 2009; 21(7):762-770.
49. Moriwaki H, Miwa Y, Tajika M, et al. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Bio- phys Res Commun 2004; 313:405–409. 
50. Yoshida T, Muto Y, Moriwaki H, et al. Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis. J Gastroenterol 1989; 24:692–698.
51. Selberg O, Bottcher J, Tusch G, et al. Identification of high- or low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients. Hepatology 1997; 25:652–657. 
52. ASPEN Board of Directors and The Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients: liver disease. JPEN 2002; 26:65SA–68SA.
53. Hara K, Yonezawa K, Weng QP, et al. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 1998; 273:14484 –14494.  

54. Proud CG. Regulation of mammalian translation factors by nutrients. Eur J Biochem 2002; 269: 5338 –5349. 
55. Bianchi GP, Marchesini G, Zoli M, et al. Oral BCAAS supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels. Hepatogastroenterology. 1992; 39(5):443-446.
56. Horst D, Grace ND, Conn HO, et al. Comparison of dietary protein with an oral, branched chain-enriched amino acid supplement in chronic portal-systemic encephalopathy: a randomized controlled trial. Hepatology. 1984;4(2):279-287.
57. Dhiman RK, Saraswat VA, Sharma BK, et al. Minimal hepatic encephalopathy: consensus statement of a working party of the Indian National Association for Study of the Liver. J Gastroenterol Hepatol. 2010;25(6):1029-1041. 
58. Bajaj JS, Cordoba J, Mullen KD, et al. Review article: the design of clinical trials in hepatic encephalopathy—an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Aliment Pharmacol Ther. 2011; 33(7):739-747.
59. Kato A, Tanaka H, Kawaguchi T, et al. Nutritional Management contributes to improvement in minimal hepatic encephalopathy and quality of life in patients with liver cirrhosis; a preliminary, prospective open-label study. Hepatol Res. 2013; 43(5):452-458. 
60. Shibayama A, Nakajima H, Tokuue H. Muscle function and nutritional assessment in chronic liver disease. Jpn J Nutr Assessment 1994; 11: 383–6.
61. Suzuki K, Kato A, Onodera K, et al. Quality of life in patients with liver cirrhosis: effect of oral administration with branched-chain amino acid granules. Kan Tan Sui (Japan) 1999; 38: 817–21.
62. Naohiro Kawamura, Hiroshi Nakajima, Shinichi Takashi Administration of granulated BCAAS and quality of life The Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan Hepatology Research 30S (2004) S42–S45.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available