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Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis.

Abstract

Branched-chain amino acids (BCAAs) constituting of valine, leucine, and isoleucine act as both substrates of proteins and as key regulators for various nutrient metabolisms. Patients with liver cirrhosis frequently lack sufficient BCAAs and therefore suffer from various metabolic disorders. Hepatic encephalopathy (HE) is a severe metabolic disorder with neurologic manifestations such as flapping tremors and coma in patients with liver cirrhosis. In addition, a mild form of HE known as minimal HE (MHE) is an important social issue because it occurs in up to 80% of patients with chronic liver disease and affects prognosis and activities of daily living, possibly resulting in falls and motor vehicle accidents. Although HE/MHE can be caused by various pathological conditions, including in an accumulation of mercaptans, short-chain fatty acids, and alterations in the gut flora, hyperammonemia has also been implicated in an important pathogenesis of HE/MHE. Besides urea cycle of liver, ammonia can be detoxified in the skeletal muscles by the amidation process for glutamine synthesis using BCAAs. Thus, BCAA supplementation may enhance detoxification of ammonia in skeletal muscle and may be a possible therapeutic strategy for HE/MHE. In this review, we summarize the clinical impacts of BCAA supplementation on HE/MHE and discuss possible mechanisms for a BCAA-induced improvement of HE/MHE. Furthermore, we present some modifications of oral BCAA therapy for improvement of efficacy in HE treatment. We also briefly describe pleiotropic benefits of BCAAs on life-threatening events and overall prognosis in patients with liver cirrhosis.

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  • Authors+Show Affiliations

    ,

    Takumi Kawaguchi, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Email: takumi@med.kurume-u.ac.jp.

    ,

    Source

    MeSH

    Administration, Oral
    Amino Acids
    Amino Acids, Branched-Chain
    Ammonia
    Dietary Supplements
    Hepatic Encephalopathy
    Humans
    Liver Cirrhosis
    Muscle, Skeletal
    Zinc

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    23945292

    Citation

    Kawaguchi, Takumi, et al. "Effects of Oral Branched-chain Amino Acids On Hepatic Encephalopathy and Outcome in Patients With Liver Cirrhosis." Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition, vol. 28, no. 5, 2013, pp. 580-8.
    Kawaguchi T, Taniguchi E, Sata M. Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis. Nutr Clin Pract. 2013;28(5):580-8.
    Kawaguchi, T., Taniguchi, E., & Sata, M. (2013). Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis. Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition, 28(5), pp. 580-8. doi:10.1177/0884533613496432.
    Kawaguchi T, Taniguchi E, Sata M. Effects of Oral Branched-chain Amino Acids On Hepatic Encephalopathy and Outcome in Patients With Liver Cirrhosis. Nutr Clin Pract. 2013;28(5):580-8. PubMed PMID: 23945292.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis. AU - Kawaguchi,Takumi, AU - Taniguchi,Eitaro, AU - Sata,Michio, Y1 - 2013/08/14/ PY - 2013/8/16/entrez PY - 2013/8/16/pubmed PY - 2014/4/11/medline KW - ammonia KW - branched chain amino acids KW - cognitive impairment KW - end-stage liver disease KW - hepatic encephalopathy KW - liver diseases KW - nutrition therapy SP - 580 EP - 8 JF - Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition JO - Nutr Clin Pract VL - 28 IS - 5 N2 - Branched-chain amino acids (BCAAs) constituting of valine, leucine, and isoleucine act as both substrates of proteins and as key regulators for various nutrient metabolisms. Patients with liver cirrhosis frequently lack sufficient BCAAs and therefore suffer from various metabolic disorders. Hepatic encephalopathy (HE) is a severe metabolic disorder with neurologic manifestations such as flapping tremors and coma in patients with liver cirrhosis. In addition, a mild form of HE known as minimal HE (MHE) is an important social issue because it occurs in up to 80% of patients with chronic liver disease and affects prognosis and activities of daily living, possibly resulting in falls and motor vehicle accidents. Although HE/MHE can be caused by various pathological conditions, including in an accumulation of mercaptans, short-chain fatty acids, and alterations in the gut flora, hyperammonemia has also been implicated in an important pathogenesis of HE/MHE. Besides urea cycle of liver, ammonia can be detoxified in the skeletal muscles by the amidation process for glutamine synthesis using BCAAs. Thus, BCAA supplementation may enhance detoxification of ammonia in skeletal muscle and may be a possible therapeutic strategy for HE/MHE. In this review, we summarize the clinical impacts of BCAA supplementation on HE/MHE and discuss possible mechanisms for a BCAA-induced improvement of HE/MHE. Furthermore, we present some modifications of oral BCAA therapy for improvement of efficacy in HE treatment. We also briefly describe pleiotropic benefits of BCAAs on life-threatening events and overall prognosis in patients with liver cirrhosis. SN - 1941-2452 UR - https://www.unboundmedicine.com/medline/citation/23945292/Effects_of_oral_branched_chain_amino_acids_on_hepatic_encephalopathy_and_outcome_in_patients_with_liver_cirrhosis_ L2 - https://doi.org/10.1177/0884533613496432 DB - PRIME DP - Unbound Medicine ER -