Supplementation with Synbiotics and/or Branched Chain Amino Acids in Hepatic Encephalopathy: A Pilot Randomised Placebo-Controlled Clinical Study

Nutrients. 2019 Aug 6;11(8):1810. doi: 10.3390/nu11081810.


Introduction: Hepatic encephalopathy (HE) is common in patients with cirrhosis and is characterised by reduced hepatic ammonia clearance. This is accompanied by alterations in gut bacteria that may be ameliorated with synbiotics (pro- and prebiotics). Branched chain amino acids (BCAAs) are thought to have a role in the detoxification of ammonia. We investigated the effects of the administration of synbiotics and/or BCAAs in treating HE.

Methods: Participants with overt HE were randomised in a blinded placebo-controlled study to receive synbiotics, BCAAs, or a combination of BCAAs and Synbiotics. Relevant biochemical and nutritional data and depression and anxiety scores (DASS-21) were collected at entry, 4 weeks, and on completion, at 8 weeks. The Trail Making Test (TMT) and Inhibitory Control Test (ICT) were used to assess cognitive function in patients withHE. Results were analysed using linear mixed effects regression analyses.

Results: Sixty-one participants were enrolled and 49 who returned for at least 1 follow-up review were included in the intention to treat analysis. The mean age was 55.8 ± 6.1 years and 86% were males. Despite evidence of a placebo effect, there was significant improvement in TMT B and ICT weighted lures in participants who received combined synbiotics/BCAAs treatment compared to placebo at study completion (p ≤ 0.05). Cognitive improvement occurred without a significant change in ammonia levels.

Conclusion: To our knowledge, this is the first study reporting that combined synbiotics and BCAAs improve HE, and that may be beneficial in the management of HE. A larger study is needed to confirm these results.

Keywords: branched chain amino acids; cognition; hepatic encephalopathy; inhibitory control test; synbiotics; trail making test.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Amino Acids, Branched-Chain / administration & dosage*
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Hepatic Encephalopathy / drug therapy*
  • Hepatic Encephalopathy / etiology
  • Humans
  • Liver Cirrhosis / complications
  • Male
  • Middle Aged
  • Pilot Projects
  • Synbiotics / administration & dosage*


  • Amino Acids, Branched-Chain