Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis.
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.
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.
Takumi
T
Kawaguchi
Eitaro
E
Taniguchi
Michio
M
Sata
D000284:Administration, Oral; D000596:Amino Acids / Q000008:administration & dosage; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage*; D000641:Ammonia / Q000378:metabolism; D019587:Dietary Supplements; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D000641:Ammonia; D015032:Zinc
ammonia; branched chain amino acids; cognitive impairment; end-stage liver disease; hepatic encephalopathy; liver diseases; nutrition therapy