Takumi Kawaguchi, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Email:
Nutr Clin Pract. 2013 Oct;28(5):580-8. doi: 10.1177/0884533613496432. Epub 2013 Aug 14.
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.
支链氨基酸（BCAAs）由缬氨酸、亮氨酸和异亮氨酸组成，它们既是蛋白质的底物，也是各种营养代谢的关键调节剂。肝硬化患者常缺乏足够的支链氨基酸，因此会遭受各种代谢紊乱。肝性脑病（HE）是一种严重的代谢紊乱，其特征为肝性昏迷的神经系统表现，如扑翼震颤和昏迷。此外，一种称为轻微肝性脑病（MHE）的轻度肝性脑病是一个重要的社会问题，因为它发生在多达 80%的慢性肝病患者中，并影响预后和日常生活活动，可能导致跌倒和机动车事故。尽管 HE/MHE 可能由多种病理状况引起，包括硫醇、短链脂肪酸和肠道菌群改变的积累，但血氨升高也与 HE/MHE 的重要发病机制有关。除了肝脏的尿素循环外，氨还可以在骨骼肌中通过支链氨基酸的酰胺化过程解毒，用于谷氨酰胺合成。因此，BCAA 补充可能增强骨骼肌中氨的解毒作用，可能是治疗 HE/MHE 的一种潜在治疗策略。在这篇综述中，我们总结了 BCAA 补充对 HE/MHE 的临床影响，并讨论了 BCAA 诱导改善 HE/MHE 的可能机制。此外，我们还提出了一些口服 BCAA 治疗的改进方法，以提高 HE 治疗的疗效。我们还简要描述了 BCAAs 对肝硬化患者危及生命的事件和总体预后的多效性益处。
