Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. 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.

    Article  CAS  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. Plauth M, Merli M, Kondrup J, et al. ESPEN guidelines for nutrition in liver disease and transplantation. Clin Nutr. 1997;16:43–55.

    Article  CAS  PubMed  Google Scholar 

  5. Greco AV, Mingrone G, Benedetti G, et al. Daily energy and substrate metabolism in patients with cirrhosis. Hepatology. 1998;27:346–50.

    Article  CAS  PubMed  Google Scholar 

  6. Tajika M, Kato M, Mohri H, et al. Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition. 2002;18:229–34.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. Lautz HU, Selberg O, Körber J, et al. Protein-calorie malnutrition in liver cirrhosis. Clin Investig. 1992;70(6):478–86.

    Article  CAS  PubMed  Google Scholar 

  16. Kachaamy T, Bajaj JS, Heuman DM. Muscle and mortality in cirrhosis. Clin Gastroenterol Hepatol. 2012;10(2):100–2.

    Article  PubMed  Google Scholar 

  17. 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.

    Article  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. Plauth M, Cabré E, Campillo B, et al. ESPEN guidelines on parenteral nutrition: hepatology. Clin Nutr. 2009;28:436–44.

    Article  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.

    Article  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. Yoshizumi T, Nakamura T, Yamane M, et al. Abdominal fat: standardized technique for measurement at CT. Radiology. 1999;211:283–6.

    Article  CAS  PubMed  Google Scholar 

  25. 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.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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.

    Article  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. Kawaguchi T, Izumi N, Charlton MR, et al. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology. 2011;54:1063–70.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    CAS  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

    Article  CAS  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed  Google Scholar 

  37. Nakaya Y, Okita K, Suzuki K, et al. BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition. 2007;23:113–20.

    Article  CAS  PubMed  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. 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.

    Article  PubMed  Google Scholar 

  41. 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.

    Article  CAS  PubMed  Google Scholar 

  42. 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.

    Article  CAS  PubMed  Google Scholar 

  43. Englesbe MJ, Patel SP, He K, et al. Sarcopenia and mortality after liver transplantation. J Am Coll Surg. 2010;211:271–8.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 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.

    Article  CAS  PubMed  Google Scholar 

  45. 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.

    Article  CAS  PubMed  Google Scholar 

  46. 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.

    Article  PubMed  Google Scholar 

  47. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the medical staff at Eguchi Hospital and Professor Kyuichi Tanikawa (International Institute for Liver Research) for excellent advice. This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (2010) (#22590741 to Y.E.).

Author information

Authors and Affiliations

  1. Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan

    Yoichiro Kitajima, Hirokazu Takahashi, Takumi Akiyama, Kenichiro Murayama, Shinji Iwane, Takuya Kuwashiro, Kenichi Tanaka & Keizo Anzai

  2. Liver Center, Saga Medical School, Saga, Japan

    Yuichiro Eguchi

  3. Department of Clinical Gastroenterology, Eguchi Hospital, Ogi, Japan

    Yoichiro Kitajima, Naofumi Ono & Takahisa Eguchi

  4. Hepatobiliary and Pancreatology Division, Department of Internal Medicine, Saga Prefectural Hospital Kosei-kan, Saga, Japan

    Seiji Kawazoe

Authors
  1. Yoichiro Kitajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hirokazu Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takumi Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenichiro Murayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinji Iwane
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takuya Kuwashiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kenichi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Seiji Kawazoe
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Naofumi Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takahisa Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Keizo Anzai
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yuichiro Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuichiro Eguchi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPTX 242 kb)

Supplementary material 2 (DOC 104 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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 53, 427–437 (2018). https://doi.org/10.1007/s00535-017-1370-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-017-1370-x

Keywords

Search

Navigation