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Published in: Journal of Gastroenterology 3/2018

01-03-2018 | Original Article—Liver, Pancreas, and Biliary Tract

Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis

Authors: Yoichiro Kitajima, Hirokazu Takahashi, Takumi Akiyama, Kenichiro Murayama, Shinji Iwane, Takuya Kuwashiro, Kenichi Tanaka, Seiji Kawazoe, Naofumi Ono, Takahisa Eguchi, Keizo Anzai, Yuichiro Eguchi

Published in: Journal of Gastroenterology | Issue 3/2018

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Abstract

Background

Liver cirrhosis induces marked metabolic disorders, protein-energy malnutrition, and sarcopenia. The objective of the study reported here was to investigate the effects of dietary branched-chain amino acids (BCAAs) on systemic glucose metabolism, skeletal muscle, and prognosis of patients with liver cirrhosis.

Methods

Japanese patients with liver cirrhosis (n = 21) were enrolled into a longitudinal study in which their diets were supplemented with BCAAs. We evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI) and intramuscular adipose tissue content (IMAC) using computed tomography.

Results

After 48 weeks of supplementation with BCAAs, there were no changes in glucose metabolism and skeletal muscle findings. In patients with ameliorated hypoalbuminemia, IMAC was significantly decreased and SAI was preserved concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels (P < 0.01 each). In patients without increased albumin levels, IMAC was significantly increased and the SAI was significantly decreased (P < 0.01 each). Liver-related event-free survival rates for 72 months were 63.6% in patients with decreased IMAC and 20.0% in patients with increased IMAC.

Conclusions

Amelioration of hypoalbuminemia associated with BCAA supplementation correlated with decreased fat accumulation in skeletal muscle, maintenance of skeletal muscle mass, and improved glucose sensitivity, all factors which may contribute to improving the survival of patients with liver cirrhosis.
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Literature
1.
go back to reference Gross CR, Malinchoc M, Kim WR, et al. Quality of life before and after liver transplantation for cholestatic liver disease. Hepatology. 1999;29:356–64.CrossRefPubMed Gross CR, Malinchoc M, Kim WR, et al. Quality of life before and after liver transplantation for cholestatic liver disease. Hepatology. 1999;29:356–64.CrossRefPubMed
2.
go back to reference 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;124:1792–801.CrossRefPubMed 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;124:1792–801.CrossRefPubMed
3.
go back to reference Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol. 2005;3:705–13.CrossRefPubMed Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol. 2005;3:705–13.CrossRefPubMed
4.
go back to reference Plauth M, Merli M, Kondrup J, et al. ESPEN guidelines for nutrition in liver disease and transplantation. Clin Nutr. 1997;16:43–55.CrossRefPubMed Plauth M, Merli M, Kondrup J, et al. ESPEN guidelines for nutrition in liver disease and transplantation. Clin Nutr. 1997;16:43–55.CrossRefPubMed
5.
go back to reference Greco AV, Mingrone G, Benedetti G, et al. Daily energy and substrate metabolism in patients with cirrhosis. Hepatology. 1998;27:346–50.CrossRefPubMed Greco AV, Mingrone G, Benedetti G, et al. Daily energy and substrate metabolism in patients with cirrhosis. Hepatology. 1998;27:346–50.CrossRefPubMed
6.
go back to reference Tajika M, Kato M, Mohri H, et al. Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition. 2002;18:229–34.CrossRefPubMed Tajika M, Kato M, Mohri H, et al. Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition. 2002;18:229–34.CrossRefPubMed
7.
go back to reference Moriwaki H, Miwa Y, Tajika M, et al. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Biophys Res Commun. 2004;313:405–9.CrossRefPubMed Moriwaki H, Miwa Y, Tajika M, et al. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Biophys Res Commun. 2004;313:405–9.CrossRefPubMed
8.
go back to reference Hidaka H, Nakazawa T, Kutsukake S, et al. The efficacy of nocturnal administration of branched-chain amino acid granules to improve quality of life in patients with cirrhosis. J Gastroenterol. 2013;48:269–70.CrossRefPubMed Hidaka H, Nakazawa T, Kutsukake S, et al. The efficacy of nocturnal administration of branched-chain amino acid granules to improve quality of life in patients with cirrhosis. J Gastroenterol. 2013;48:269–70.CrossRefPubMed
9.
go back to reference Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol. 2005;3:705–13.CrossRefPubMed Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol. 2005;3:705–13.CrossRefPubMed
10.
go back to reference 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;124:1792–801.CrossRefPubMed 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;124:1792–801.CrossRefPubMed
11.
go back to reference Urata Y, Okita K, Korenaga K, et al. The effect of supplementation with branched-chain amino acids in patients with liver cirrhosis. Hepatol Res. 2007;37:510–6.CrossRefPubMed Urata Y, Okita K, Korenaga K, et al. The effect of supplementation with branched-chain amino acids in patients with liver cirrhosis. Hepatol Res. 2007;37:510–6.CrossRefPubMed
12.
go back to reference Tabaru A, Shirohara H, Moriyama A, et al. Effects of branched-chain-enriched amino acid solution on insulin and glucagon secretion and blood glucose level in liver cirrhosis. Scand J Gastroenterol. 1998;33:853–9.CrossRefPubMed Tabaru A, Shirohara H, Moriyama A, et al. Effects of branched-chain-enriched amino acid solution on insulin and glucagon secretion and blood glucose level in liver cirrhosis. Scand J Gastroenterol. 1998;33:853–9.CrossRefPubMed
13.
go back to reference Kawaguchi T, Taniguchi E, Itou M, 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;27:1287–92.PubMed Kawaguchi T, Taniguchi E, Itou M, 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;27:1287–92.PubMed
14.
go back to reference Nishitani S, Takehana K, Fujitani S, et al. Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2005;288:G1292–300.CrossRefPubMed Nishitani S, Takehana K, Fujitani S, et al. Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2005;288:G1292–300.CrossRefPubMed
15.
go back to reference Lautz HU, Selberg O, Körber J, et al. Protein-calorie malnutrition in liver cirrhosis. Clin Investig. 1992;70(6):478–86.CrossRefPubMed Lautz HU, Selberg O, Körber J, et al. Protein-calorie malnutrition in liver cirrhosis. Clin Investig. 1992;70(6):478–86.CrossRefPubMed
16.
go back to reference Kachaamy T, Bajaj JS, Heuman DM. Muscle and mortality in cirrhosis. Clin Gastroenterol Hepatol. 2012;10(2):100–2.CrossRefPubMed Kachaamy T, Bajaj JS, Heuman DM. Muscle and mortality in cirrhosis. Clin Gastroenterol Hepatol. 2012;10(2):100–2.CrossRefPubMed
17.
go back to reference Kitajima Y, Eguchi Y, Ishibashi E, et al. Age-related fat deposition in multifidus muscle could be a marker for nonalcoholic fatty liver disease. J Gastroenterol. 2010;45:218–24.CrossRefPubMed Kitajima Y, Eguchi Y, Ishibashi E, et al. Age-related fat deposition in multifidus muscle could be a marker for nonalcoholic fatty liver disease. J Gastroenterol. 2010;45:218–24.CrossRefPubMed
18.
go back to reference Kitajima Y, Hyogo H, Sumida Y, et al. The severity of nonalcoholic steatohepatitis is associated with substitution of adipose tissue in skeletal muscle. J Gastroenterol Hepatol. 2013;28(9):1507–14.CrossRefPubMed Kitajima Y, Hyogo H, Sumida Y, et al. The severity of nonalcoholic steatohepatitis is associated with substitution of adipose tissue in skeletal muscle. J Gastroenterol Hepatol. 2013;28(9):1507–14.CrossRefPubMed
19.
go back to reference Plauth M, Cabré E, Campillo B, et al. ESPEN guidelines on parenteral nutrition: hepatology. Clin Nutr. 2009;28:436–44.CrossRefPubMed Plauth M, Cabré E, Campillo B, et al. ESPEN guidelines on parenteral nutrition: hepatology. Clin Nutr. 2009;28:436–44.CrossRefPubMed
20.
go back to reference Haffner SM, Kennedy E, Gonzalez C, et al. A prospective analysis of the HOMA model. The Mexico City Diabetes Study. Diabetes Care. 1996;19:1138–41.CrossRefPubMed Haffner SM, Kennedy E, Gonzalez C, et al. A prospective analysis of the HOMA model. The Mexico City Diabetes Study. Diabetes Care. 1996;19:1138–41.CrossRefPubMed
21.
go back to reference Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402–10.CrossRefPubMed Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402–10.CrossRefPubMed
22.
go back to reference Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.CrossRefPubMed Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.CrossRefPubMed
23.
go back to reference Piekarski J, Goldberg HI, Royal SA, et al. Difference between liver and spleen CT number in the normal adult: its usefulness in predicting the presence of diffuse liver disease. Radiology. 1980;137:727–9.CrossRefPubMed Piekarski J, Goldberg HI, Royal SA, et al. Difference between liver and spleen CT number in the normal adult: its usefulness in predicting the presence of diffuse liver disease. Radiology. 1980;137:727–9.CrossRefPubMed
24.
go back to reference Yoshizumi T, Nakamura T, Yamane M, et al. Abdominal fat: standardized technique for measurement at CT. Radiology. 1999;211:283–6.CrossRefPubMed Yoshizumi T, Nakamura T, Yamane M, et al. Abdominal fat: standardized technique for measurement at CT. Radiology. 1999;211:283–6.CrossRefPubMed
25.
go back to reference Janssen I, Baumgartner RN, Ross R, et al. Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am J Epidemiol. 2004;159(4):413–21.CrossRefPubMed Janssen I, Baumgartner RN, Ross R, et al. Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am J Epidemiol. 2004;159(4):413–21.CrossRefPubMed
26.
go back to reference Mourtzakis M, Prado CM, Lieffers JR, et al. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33(5):997–1006.CrossRefPubMed Mourtzakis M, Prado CM, Lieffers JR, et al. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33(5):997–1006.CrossRefPubMed
27.
go back to reference Ling CH, de Craen AJ, Slagboom PE, et al. Accuracy of direct segmental multi-frequency bioimpedance analysis in the assessment of total body and segmental body composition in middle-aged adult population. Clin Nutr. 2011;30(5):610–5.CrossRefPubMed Ling CH, de Craen AJ, Slagboom PE, et al. Accuracy of direct segmental multi-frequency bioimpedance analysis in the assessment of total body and segmental body composition in middle-aged adult population. Clin Nutr. 2011;30(5):610–5.CrossRefPubMed
28.
go back to reference Janssen I, Heymsfield SB, Baumgartner RN, et al. Estimation of skeletal muscle mass by bioelectrical impedance analysis. J Appl Physiol. 2000;89(2):465–71.CrossRefPubMed Janssen I, Heymsfield SB, Baumgartner RN, et al. Estimation of skeletal muscle mass by bioelectrical impedance analysis. J Appl Physiol. 2000;89(2):465–71.CrossRefPubMed
29.
go back to reference Kawaguchi T, Izumi N, Charlton MR, et al. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology. 2011;54:1063–70.CrossRefPubMed Kawaguchi T, Izumi N, Charlton MR, et al. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology. 2011;54:1063–70.CrossRefPubMed
30.
go back to reference Ijichi C, Matsumura T, Tsuji T, et al. 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.CrossRefPubMed Ijichi C, Matsumura T, Tsuji T, et al. 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.CrossRefPubMed
31.
go back to reference Nishitani S, Ijichi C, Takehana K, et al. Pharmacological activities of branched-chain amino acids: specificity of tissue and signal transduction. Biochem Biophys Res Commun. 2004;313:387–9.CrossRefPubMed Nishitani S, Ijichi C, Takehana K, et al. Pharmacological activities of branched-chain amino acids: specificity of tissue and signal transduction. Biochem Biophys Res Commun. 2004;313:387–9.CrossRefPubMed
32.
go back to reference Matsumura T, Morinaga Y, Fujitani S, et al. Oral administration of branched-chain amino acids activates the mTOR signal in cirrhotic rat liver. Hepatol Res. 2005;33:27–32.CrossRefPubMed Matsumura T, Morinaga Y, Fujitani S, et al. Oral administration of branched-chain amino acids activates the mTOR signal in cirrhotic rat liver. Hepatol Res. 2005;33:27–32.CrossRefPubMed
33.
go back to reference Hayashi M, Ohnishi H, Kawade 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.PubMed Hayashi M, Ohnishi H, Kawade 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.PubMed
34.
go back to reference Higuchi N, Kato M, Miyazaki M, 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;112:30–8.CrossRefPubMed Higuchi N, Kato M, Miyazaki M, 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;112:30–8.CrossRefPubMed
35.
go back to reference Nishimura J, Masaki T, Arakawa M, et al. 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.CrossRefPubMed Nishimura J, Masaki T, Arakawa M, et al. 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.CrossRefPubMed
36.
go back to reference Arakawa M, Masaki T, Nishimura J, et al. 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;58:161–70.CrossRefPubMed Arakawa M, Masaki T, Nishimura J, et al. 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;58:161–70.CrossRefPubMed
37.
go back to reference Nakaya Y, Okita K, Suzuki K, et al. BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition. 2007;23:113–20.CrossRefPubMed Nakaya Y, Okita K, Suzuki K, et al. BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition. 2007;23:113–20.CrossRefPubMed
38.
go back to reference Ichikawa T, Naota T, Miyaaki H, et al. Effect of an oral branched chain amino acid-enriched snack in cirrhotic patients with sleep disturbance. Hepatol Res. 2010;40:971–8.CrossRefPubMed Ichikawa T, Naota T, Miyaaki H, et al. Effect of an oral branched chain amino acid-enriched snack in cirrhotic patients with sleep disturbance. Hepatol Res. 2010;40:971–8.CrossRefPubMed
39.
go back to reference Nishitani S, Matsumura T, Fujitani S, et al. Leucine promotes glucose uptake in skeletal muscles of rats. Biochem Biophys Res Commun. 2002;299:693–6.CrossRefPubMed Nishitani S, Matsumura T, Fujitani S, et al. Leucine promotes glucose uptake in skeletal muscles of rats. Biochem Biophys Res Commun. 2002;299:693–6.CrossRefPubMed
40.
go back to reference Müller MJ, Böker KH, Selberg O. Metabolism of energy-yielding substrates in patients with liver cirrhosis. Metabolism of energy-yielding substrates in patients with liver cirrhosis. Clin Investig. 1994;72(8):568–79.CrossRefPubMed Müller MJ, Böker KH, Selberg O. Metabolism of energy-yielding substrates in patients with liver cirrhosis. Metabolism of energy-yielding substrates in patients with liver cirrhosis. Clin Investig. 1994;72(8):568–79.CrossRefPubMed
41.
go back to reference Campillo B, Bories PN, Pornin B, et al. Influence of liver failure, ascites, and energy expenditure on the response to oral nutrition in alcoholic liver cirrhosis. Nutrition. 1997;13(7–8):613–21.CrossRefPubMed Campillo B, Bories PN, Pornin B, et al. Influence of liver failure, ascites, and energy expenditure on the response to oral nutrition in alcoholic liver cirrhosis. Nutrition. 1997;13(7–8):613–21.CrossRefPubMed
42.
go back to reference Selberg O, Böttcher J, Tusch G, et al. Identification of high- and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients. Hepatology. 1997;25(3):652–7.CrossRefPubMed Selberg O, Böttcher J, Tusch G, et al. Identification of high- and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients. Hepatology. 1997;25(3):652–7.CrossRefPubMed
44.
go back to reference Kamachi S, Mizuta T, Otsuka T, et al. Sarcopenia is a risk factor for the recurrence of hepatocellular carcinoma after curative treatment. Hepatol Res. 2016;46(2):201–8.CrossRefPubMed Kamachi S, Mizuta T, Otsuka T, et al. Sarcopenia is a risk factor for the recurrence of hepatocellular carcinoma after curative treatment. Hepatol Res. 2016;46(2):201–8.CrossRefPubMed
45.
go back to reference Campillo B, Fouet P, Bonnet JC, et al. Submaximal oxygen consumption in liver cirrhosis. Evidence of severe functional aerobic impairment. J Hepatol. 1990;10(2):163–7.CrossRefPubMed Campillo B, Fouet P, Bonnet JC, et al. Submaximal oxygen consumption in liver cirrhosis. Evidence of severe functional aerobic impairment. J Hepatol. 1990;10(2):163–7.CrossRefPubMed
46.
go back to reference 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):1966–75.CrossRefPubMed 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):1966–75.CrossRefPubMed
47.
go back to reference 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):E193–200.CrossRefPubMed 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):E193–200.CrossRefPubMed
Metadata
Title
Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis
Authors
Yoichiro Kitajima
Hirokazu Takahashi
Takumi Akiyama
Kenichiro Murayama
Shinji Iwane
Takuya Kuwashiro
Kenichi Tanaka
Seiji Kawazoe
Naofumi Ono
Takahisa Eguchi
Keizo Anzai
Yuichiro Eguchi
Publication date
01-03-2018
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 3/2018
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-017-1370-x

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Acknowledgements

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