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Effect of isolated branched chain amino acids in the serum pH and cerebral blood flow of cirrhotic patients: a randomized, double blind controlled trial

Grant number: 13/11761-2
Support type:Regular Research Grants
Duration: February 01, 2014 - July 31, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Fernando Gomes Romeiro
Grantee:Fernando Gomes Romeiro
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers:Carlos Antonio Caramori ; Katia Hiromoto Koga ; Luiz Eduardo Gomes Garcia Betting ; Sonia Marta Moriguchi

Abstract

Hepatic encephalopathy (HE) is a serious complication of cirrhosis. The swelling of astrocytes, caused by the conversion of ammonia to glutamine into the brain, is a leading cause of persistent HE, impairing the cerebral blood flow. It has been shown that alkalemia is a trigger for HE, but few studies have evaluated the serum pH in these patients.The use of branched chain amino acids (BCAA) is recommended for patients with cirrhosis and HE in specific Guidelines. BCAA increases cerebral blood flow in these patients within few hours after ingestion, but the involved mechanisms remains unknown. The hypothesis of this study is that as soon as the patient ingests the BCAA, its metabolization to ketoacids led to a slight reduction of the serum pH, increasing cerebral blood flow. After a more prolonged BCAA ingestion, the muscle mass changes will favor ammonia metabolization in muscles, preventing its cerebral conversion to glutamine and reducing astrocyte swelling.Until now there are no studies comparing outcomes of supplementation with different BCAA in patients with cirrhosis and HE. The use of isolated leucine promotes muscle mass changes, which is extremely important for patients with cirrhosis. On the other hand, the serum dosage of isoleucine acts as an independent marker of HE. This study will assess electroencephalographic, biochemical and imaging exams performed immediately and after prolonged BCAA use, comparing the effects obtained by leucine and isoleucine. The study will be a prospective, randomized, double-blind controlled trial comparing the aforementioned parameters before and after the treatments. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROMEIRO, FERNANDO GOMES; IETSUGU, MARJORIE DO VAL; FRANZONI, LETICIA DE CAMPOS; AUGUSTI, LAIS; ALVAREZ, MATHEUS; AMARAL SANTOS, LIVIA ALVES; LIMA, TALLES BAZEI; KOGA, KATIA HIROMOTO; MORIGUCHI, SONIA MARTA; CARAMORI, CARLOS ANTONIO; SILVA, GIOVANNI FARI; GOMES GARCIA BETTING, LUIZ EDUARDO. Which of the branched-chain amino acids increases cerebral blood flow in hepatic encephalopathy? A double-blind randomized trial. NEUROIMAGE-CLINICAL, v. 19, p. 302-310, 2018. Web of Science Citations: 1.
AUGUSTI, L.; FRANZONI, L. C.; SANTOS, L. A. A.; LIMA, T. B.; IETSUGU, M. V.; KOGA, K. H.; MORIGUCHI, S. M.; BETTING, L. E.; CARAMORI, C. A.; SILVA, G. F.; ROMEIRO, F. G. Lower values of handgrip strength and adductor pollicis muscle thickness are associated with hepatic encephalopathy manifestations in cirrhotic patients. METABOLIC BRAIN DISEASE, v. 31, n. 4, p. 909-915, AUG 2016. Web of Science Citations: 6.
ROMEIRO, FERNANDO GOMES; AUGUSTI, LAIS. Nutritional assessment in cirrhotic patients with hepatic encephalopathy. WORLD JOURNAL OF HEPATOLOGY, v. 7, n. 30, p. 2940-2954, DEC 28 2015. Web of Science Citations: 10.

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