Branched-chain amino acids as pharmacological nutrients in chronic liver disease

Hepatology

Volumn 54, Issue 3, 2011, Pages 1063-1070

  Kawaguchi, Takumi ^a   Izumi, Namiki ^b   Charlton, Michael R ^c   Sata, Michio ^a  

^a Department of Medicine ^*  (Japan)

^b MUSASHINO RED CROSS HOSPITAL   (Japan)

^c MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRANCHED CHAIN AMINO ACID; GLUCOSE 6 PHOSPHATASE; GLUCOSE TRANSPORTER 1; INSULIN; LEUCINE; LIVER X RECEPTOR ALPHA; MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE; POLYPYRIMIDINE TRACT BINDING PROTEIN; PROTEIN KINASE B; PROTEIN KINASE C; S6 KINASE; SERUM ALBUMIN; SOMATOMEDIN C RECEPTOR; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TRYPTOPHAN; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3;

ADIPOSE TISSUE; ALBUMIN BLOOD LEVEL; ANGIOGENESIS; BRAIN BLOOD FLOW; CELL MIGRATION; CELL PROLIFERATION; CHRONIC LIVER DISEASE; DIET SUPPLEMENTATION; DRUG FORMULATION; DRUG SAFETY; EPITHELIAL MESENCHYMAL TRANSITION; FATIGUE; FATTY ACID OXIDATION; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; HEPATIC ENCEPHALOPATHY; HEPATITIS C; HOSPITAL ADMISSION; HOSPITALIZATION; HUMAN; HYPERINSULINEMIA; IN VITRO STUDY; INSULIN BINDING; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIVER; LIVER CARCINOGENESIS; LIVER CELL; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FAILURE; LYMPHOCYTE COUNT; MALNUTRITION; MOLECULAR INTERACTION; MORTALITY; MUSCLE; MUSCLE CRAMP; NATURAL KILLER T CELL; NEUTROPHIL; OBESITY; OUTCOME ASSESSMENT; OXIDATIVE STRESS; PATIENT COMPLIANCE; PHAGOCYTE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; QUALITY OF LIFE; RADIOFREQUENCY ABLATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RNA TRANSPORT; SKELETAL MUSCLE; SLEEP DISORDER; UPREGULATION;

ALBUMINS; AMINO ACIDS, BRANCHED-CHAIN; CARCINOMA, HEPATOCELLULAR; DIETARY SUPPLEMENTS; HUMANS; INSULIN RESISTANCE; LIVER CIRRHOSIS; LIVER NEOPLASMS; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 80052025887     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.24412     Document Type: Review

References (79)

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. Yamato M, Muto Y, Yoshida T, Kato M, Moriwaki M. Clearance rate of plasma branched-chain amino acids correlates significantly with blood ammonia level in patients with liver cirrhosis. Int Hepatol Commun 1995; 3: 91-96.
4. Okuno M, Moriwaki H, Kato M, Muto Y, Kojima S. Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes. Biochem Biophys Res Commun 1995; 214: 1045-1050.
5. Steigmann F, Szanto PB, Poulos A, Lim PE, Dubin A. Significance of serum aminograms in diagnosis and prognosis of liver diseases. J Clin Gastroenterol 1984; 6: 453-460.
6. Plauth M, Egberts EH, Hamster W, Torok M, Muller PH, Brand O, et al. Long-term treatment of latent portosystemic encephalopathy with branched-chain amino acids. A double-blind placebo-controlled crossover study. J Hepatol 1993; 17: 308-314.
7. Keshavarzian A, Meek J, Sutton C, Emery VM, Hughes EA, Hodgson HJ. Dietary protein supplementation from vegetable sources in the management of chronic portal systemic encephalopathy. Am J Gastroenterol 1984; 79: 945-949.
8. ASPEN Board of Directors and the Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr 2002; 26(suppl 1): 1SA-138SA.
9. Plauth M, Cabre E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, et al. ESPEN Guidelines on Enteral Nutrition: Liver disease. Clin Nutr 2006; 25: 285-294.
10. Suzuki K, Suzuki K, Koizumi K, Ichimura H, Oka S, Takada H, et al. Measurement of serum branched-chain amino acids to tyrosine ratio level is useful in a prediction of a change of serum albumin level in chronic liver disease. Hepatol Res 2008; 38: 267-272.
11. 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: 276-290.
12. Ijichi C, Matsumura T, Tsuji T, Eto Y. Branched-chain amino acids promote albumin synthesis in rat primary hepatocytes through the mTOR signal transduction system. Biochem Biophys Res Commun 2003; 303: 59-64.
13. Nishitani S, Takehana K, Fujitani S, Sonaka I. Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol 2005; 288: G1292-G1300.
14. She P, Reid TM, Bronson SK, Vary TC, Hajnal A, Lynch CJ, et al. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab 2007; 6: 181-194.
15. 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; 124: 1792-1801.
16. Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol 2005; 3: 705-713.
17. Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, et al. Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis. Hepatol Res 2006; 35: 204-214.
18. Kawaguchi T, Nagao Y, Matsuoka H, Ide T, Sata M. Branched-chain amino acid-enriched supplementation improves insulin resistance in patients with chronic liver disease. Int J Mol Med 2008; 22: 105-112.
19. Kakazu E, Ueno Y, Kondo Y, Fukushima K, Shiina M, Inoue J, et al. Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis. HEPATOLOGY 2009; 50: 1936-1945.
20. Nakaya Y, Okita K, Suzuki K, Moriwaki H, Kato A, Miwa Y, et al. BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition 2007; 23: 113-120.
21. Ichikawa T, Naota T, Miyaaki H, Miuma S, Isomoto H, Takeshima F, et al. Effect of an oral branched chain amino acid-enriched snack in cirrhotic patients with sleep disturbance. Hepatol Res 2010; 40: 971-978.
22. Charlton M. Branched-chain amino acid enriched supplements as therapy for liver disease. J Nutr 2006; 136(suppl 1): 295S-298S.
23. Moriwaki H, Miwa Y, Tajika M, Kato M, Fukushima H, Shiraki M. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Biophys Res Commun 2004; 313: 405-409.
24. Montoya A, Gomez-Lechon MJ, Castell JV. Influence of branched-chain amino acid composition of culture media on the synthesis of plasma proteins by serum-free cultured rat hepatocytes. In Vitro Cell Dev Biol 1989; 25: 358-364.
25. Kuwahata M, Yoshimura T, Sawai Y, Amano S, Tomoe Y, Segawa H, et al. Localization of polypyrimidine-tract-binding protein is involved in the regulation of albumin synthesis by branched-chain amino acids in HepG2 cells. J Nutr Biochem 2008; 19: 438-447.
26. 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: 387-389.
27. Kawamura-Yasui N, Kaito M, Nakagawa N, Fujita N, Ikoma J, Gabazza EC, et al. Evaluating response to nutritional therapy using the branched-chain amino acid/tyrosine ratio in patients with chronic liver disease. J Clin Lab Anal 1999; 13: 31-34.
28. Layman DK, Shiue H, Sather C, Erickson DJ, Baum J. Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss. J Nutr 2003; 133: 405-410.
29. 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: 1647-1654.
30. Ikehara O, Kawasaki N, Maezono K, Komatsu M, Konishi A. Acute and chronic treatment of L-isoleucine ameliorates glucose metabolism in glucose-intolerant and diabetic mice. Biol Pharm Bull 2008; 31: 469-472.
31. Nishitani S, Matsumura T, Fujitani S, Sonaka I, Miura Y, Yagasaki K. Leucine promotes glucose uptake in skeletal muscles of rats. Biochem Biophys Res Commun 2002; 299: 693-696.
32. Hinault C, Mothe-Satney I, Gautier N, Lawrence JC Jr, Van Obberghen E. Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in normal adipocytes treated with wortmannin and in adipocytes from db/db mice. FASEB J 2004; 18: 1894-1896.
33. Higuchi N, Kato M, Miyazaki M, Tanaka M, Kohjima M, Ito T, et al. Potential role of branched-chain amino acids in glucose metabolism through the accelerated induction of the glucose-sensing apparatus in the liver. J Cell Biochem 2011; 112: 30-38.
34. Nishimura J, Masaki T, Arakawa M, Seike M, Yoshimatsu H. Isoleucine prevents the accumulation of tissue triglycerides and upregulates the expression of PPARalpha and uncoupling protein in diet-induced obese mice. J Nutr 2010; 140: 496-500.
35. Arakawa M, Masaki T, Nishimura J, Seike M, Yoshimatsu H. The effects of branched-chain amino acid granules on the accumulation of tissue triglycerides and uncoupling proteins in diet-induced obese mice. Endocr J 2011; 58: 161-170.
36. Tabaru A, Shirohara H, Moriyama A, Otsuki M. Effects of branched-chain-enriched amino acid solution on insulin and glucagon secretion and blood glucose level in liver cirrhosis. Scand J Gastroenterol 1998; 33: 853-859.
37. Korenaga K, Korenaga M, Uchida K, Yamasaki T, Sakaida I. Effects of a late evening snack combined with alpha-glucosidase inhibitor on liver cirrhosis. Hepatol Res 2008; 38: 1087-1097.
38. Sakaida I, Tsuchiya M, Okamoto M, Okita K. Late evening snack and the change of blood glucose level in patients with liver cirrhosis. Hepatol Res 2004; 30S: 67-72.
39. Kawaguchi T, Taniguchi E, Itou M, Sumie S, Oriishi T, Matsuoka H, et al. Branched-chain amino acids improve insulin resistance in patients with hepatitis C virus-related liver disease: report of two cases. Liver Int 2007; 27: 1287-1292.
40. Tsuchiya K, Asahina Y, Izumi N. Long time oral supplementation with branched-chain amino acids improves survival and decreases recurrences in patients with hepatocellular carcinoma [in Japanese]. Nippon Shokakibyo Gakkai Zasshi 2008; 105: 808-816.
41. Iwasa J, Shimizu M, Shiraki M, Shirakami Y, Sakai H, Terakura Y, et al. Dietary supplementation with branched-chain amino acids suppresses diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db mice. Cancer Sci 2010; 101: 460-467.
42. Yoshiji H, Noguchi R, Kaji K, Ikenaka Y, Shirai Y, Namisaki T, et al. Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats. J Gastroenterol 2010; 45: 443-450.
43. Paradis V, Zalinski S, Chelbi E, Guedj N, Degos F, Vilgrain V, et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. HEPATOLOGY 2009; 49: 851-859.
44. Kawaguchi T, Yoshida T, Harada M, Hisamoto T, Nagao Y, Ide T, et al. Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol 2004; 165: 1499-1508.
45. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. HEPATOLOGY 2010; 51: 1820-1832.
46. Formisano P, Oriente F, Fiory F, Caruso M, Miele C, Maitan MA, et al. Insulin-activated protein kinase Cbeta bypasses Ras and stimulates mitogen-activated protein kinase activity and cell proliferation in muscle cells. Mol Cell Biol 2000; 20: 6323-6333.
47. Sandhu MS, Dunger DB, Giovannucci EL. Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 2002; 94: 972-980.
48. Scharf JG, Dombrowski F, Ramadori G. The IGF axis and hepatocarcinogenesis. Mol Pathol 2001; 54: 138-144.
49. Qi HL, Zhang Y, Ma J, Guo P, Zhang XY, Chen HL. Insulin/protein kinase B signalling pathway upregulates metastasis-related phenotypes and molecules in H7721 human hepatocarcinoma cell line. Eur J Biochem 2003; 270: 3795-3805.
50. Nitta T, Kim JS, Mohuczy D, Behrns KE. Murine cirrhosis induces hepatocyte epithelial mesenchymal transition and alterations in survival signaling pathways. HEPATOLOGY 2008; 48: 909-919.
51. Nakamura I, Ochiai K, Imai Y, Moriyasu F, Imawari M. Restoration of innate host defense responses by oral supplementation of branched-chain amino acids in decompensated cirrhotic patients. Hepatol Res 2007; 37: 1062-1067.
52. Fukushima H, Miwa Y, Shiraki M, Gomi I, Toda K, Kuriyama S, et al. Oral branched-chain amino acid supplementation improves the oxidized/reduced albumin ratio in patients with liver cirrhosis. Hepatol Res 2007; 37: 765-770.
53. Ohno T, Tanaka Y, Sugauchi F, Orito E, Hasegawa I, Nukaya H, et al. Suppressive effect of oral administration of branched-chain amino acid granules on oxidative stress and inflammation in HCV-positive patients with liver cirrhosis. Hepatol Res 2008; 38: 683-688.
54. Halliwell B, Gutteridge JM. The antioxidants of human extracellular fluids. Arch Biochem Biophys 1990; 280: 1-8.
55. Hayashi T, Suda K, Imai H, Era S. Simple and sensitive high-performance liquid chromatographic method for the investigation of dynamic changes in the redox state of rat serum albumin. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 772: 139-146.
56. Watanabe A, Matsuzaki S, Moriwaki H, Suzuki K, Nishiguchi S. Problems in serum albumin measurement and clinical significance of albumin microheterogeneity in cirrhotics. Nutrition 2004; 20: 351-357.
57. Sakata M, Kawaguchi T, Taniguchi E, Nakayama A, Ishizaki S, Sonaka I, et al. Oxidized albumin is associated with water retention and severity of disease in patients with chronic liver diseases. e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 2010; 5: e247-e253.
58. Ichida T, Shibasaki K, Muto Y, Satoh S, Watanabe A, Ichida F. Clinical study of an enteral branched-chain amino acid solution in decompensated liver cirrhosis with hepatic encephalopathy. Nutrition 1995; 11(suppl 2): 238-244.
59. Kajiwara K, Okuno M, Kobayashi T, Honma N, Maki T, Kato M, et al. Oral supplementation with branched-chain amino acids improves survival rate of rats with carbon tetrachloride-induced liver cirrhosis. Dig Dis Sci 1998; 43: 1572-1579.
60. Yoshida T, Muto Y, Moriwaki H, Yamato M. Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis. Gastroenterol Jpn 1989; 24: 692-698.
61. Kuroda H, Ushio A, Miyamoto Y, Sawara K, Oikawa K, Kasai K, et al. Effects of branched-chain amino acid-enriched nutrient for patients with hepatocellular carcinoma following radiofrequency ablation: a one-year prospective trial. J Gastroenterol Hepatol 2010; 25: 1550-1555.
62. Meng WC, Leung KL, Ho RL, Leung TW, Lau WY. Prospective randomized control study on the effect of branched-chain amino acids in patients with liver resection for hepatocellular carcinoma. Aust N Z J Surg 1999; 69: 811-815.
63. Poon RT, Yu WC, Fan ST, Wong J. Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial. Aliment Pharmacol Ther 2004; 19: 779-788.
64. Kumada H, Okanoue T, Onji M, Moriwaki H, Izumi N, Tanaka E, et al. Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis C virus infection for the fiscal year 2008 in Japan. Hepatol Res 2010; 40: 8-13.
65. Gross CR, Malinchoc M, Kim WR, Evans RW, Wiesner RH, Petz JL, et al. Quality of life before and after liver transplantation for cholestatic liver disease. HEPATOLOGY 1999; 29: 356-364.
66. Kawamura N, Nakajima H, Takashi SI. Administration of granulated BCAA and quality of life. Hepatol Res 2004; 30S: 42-45.
67. Cordoba J, Cabrera J, Lataif L, Penev P, Zee P, Blei AT. High prevalence of sleep disturbance in cirrhosis. HEPATOLOGY 1998; 27: 339-345.
68. Wilkinson DJ, Smeeton NJ, Watt PW. Ammonia metabolism, the brain and fatigue; revisiting the link. Prog Neurobiol 2010; 91: 200-219.
69. Huang A, Fuchs D, Widner B, Glover C, Henderson DC, Allen-Mersh TG. Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer. Br J Cancer 2002; 86: 1691-1696.
70. Davis JM, Alderson NL, Welsh RS. Serotonin and central nervous system fatigue: nutritional considerations. Am J Clin Nutr 2000; 72(suppl 2): 573S-578S.
71. Fernstrom JD. Branched-chain amino acids and brain function. J Nutr 2005; 135(suppl 6): 1539S-1546S.
72. Biswal B, Kunwar P, Natelson BH. Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling. J Neurol Sci 2011; 301: 9-11.
73. Ahl B, Weissenborn K, van den Hoff J, Fischer-Wasels D, Kostler H, Hecker H, et al. Regional differences in cerebral blood flow and cerebral ammonia metabolism in patients with cirrhosis. HEPATOLOGY 2004; 40: 73-79.
74. Iwasa M, Matsumura K, Kaito M, Ikoma J, Kobayashi Y, Nakagawa N, et al. Decrease of regional cerebral blood flow in liver cirrhosis. Eur J Gastroenterol Hepatol 2000; 12: 1001-1006.
75. Iwasa M, Matsumura K, Watanabe Y, Yamamoto M, Kaito M, Ikoma J, et al. Improvement of regional cerebral blood flow after treatment with branched-chain amino acid solutions in patients with cirrhosis. Eur J Gastroenterol Hepatol 2003; 15: 733-737.
76. Yamamoto M, Iwasa M, Matsumura K, Nakagawa Y, Fujita N, Kobayashi Y, et al. Improvement of regional cerebral blood flow after oral intake of branched-chain amino acids in patients with cirrhosis. World J Gastroenterol 2005; 11: 6792-6799.
77. Marchesini G, Bianchi G, Amodio P, Salerno F, Merli M, Panella C, et al. Factors associated with poor health-related quality of life of patients with cirrhosis. Gastroenterology 2001; 120: 170-178.
78. Sako K, Imamura Y, Nishimata H, Tahara K, Kubozono O, Tsubouchi H. Branched-chain amino acids supplements in the late evening decrease the frequency of muscle cramps with advanced hepatic cirrhosis. Hepatol Res 2003; 26: 327-329.
79. Corbani A, Manousou P, Calvaruso V, Xirouchakis I, Burroughs AK. Muscle cramps in cirrhosis: the therapeutic value of quinine. Is it underused? Dig Liver Dis 2008; 40: 794-799.