Branched-chain amino acid supplementation in adults with cirrhosis and porto-systemic encephalopathy: systematic review

Emma Louise Metcalfe, Alison Avenell, Andrew Fraser

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


BACKGROUND & AIMS: Branched-chain amino acid supplementation in porto-systemic encephalopathy remains controversial. Here, we examined the systematic review evidence for their effect on encephalopathy, hepatic decompensation, survival, infection, hospital stay and quality of life, and review data on adherence, side-effects and cost/economic evaluation.

METHODS: Four electronic databases were searched from 1980 to June 2011, with an update search in two databases in July 2013. Hand-searching was performed of references lists from included trials and six conference proceedings from 2005 to 2010. We included randomised controlled trials of branched chain amino acids versus other nutritional supplements in adults with cirrhosis and porto-systemic encephalopathy. Data extraction and quality assessment were performed by two independent assessors. Meta-analysis was performed if data were sufficient.

RESULTS: The search identified nine randomised controlled trials (436 patients in total) of branched-chain amino acid therapy for ≥2 weeks' duration. The overall quality of trials was poor. At meta-analysis, a significant improvement in the grade of encephalopathy was demonstrated in favour of branched-chain amino acids compared to other nutritional supplements (Risk Ratio 2.6, 95% Confidence Interval 1.7-3.9, p < 0.001, 2 trials, n 122) but no significant difference was found for either resolution or worsening of encephalopathy, gastrointestinal bleeding, survival or infection. Limited data suggested no difference in health-related quality of life, ascites or admission to hospital. Studies did not include cost data or economic evaluations. Side-effects appeared mild and gastrointestinal in nature.

CONCLUSIONS: Branched-chain amino acids might improve porto-systemic encephalopathy but more robust trials are needed to determine their role.

Original languageEnglish
Pages (from-to)958-965
Number of pages8
JournalClinical Nutrition
Issue number6
Early online date6 Mar 2014
Publication statusPublished - Dec 2014

Bibliographical note

Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The Health Services Research Unit, University of Aberdeen, is funded by the Chief Scientist Office of the Scottish Government Health Directorates. We also thank Ron Koretz for help with locating trials, and Alena Vasianovich for help with document translation to assess eligibility for trial inclusion.


  • branched-chain amino acids
  • cirrhosis
  • porto-systemic encephalopathy


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