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

Clin Nutr. 2014 Dec;33(6):958-65. doi: 10.1016/j.clnu.2014.02.011. Epub 2014 Mar 6.


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.

Keywords: Branched-chain amino acids; Cirrhosis; Porto-systemic encephalopathy.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Amino Acids, Branched-Chain / administration & dosage*
  • Dietary Supplements*
  • Hepatic Encephalopathy / drug therapy*
  • Humans
  • Length of Stay
  • Liver Cirrhosis / drug therapy*
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Sensitivity and Specificity
  • Treatment Outcome


  • Amino Acids, Branched-Chain