Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study

Am J Clin Nutr. 2011 Apr;93(4):799-808. doi: 10.3945/ajcn.110.007393. Epub 2011 Feb 10.


Background: Fatigue is frequently reported in hepatic encephalopathy (HE) and may be related to hyperammonemia. Acetyl-L-carnitine (ALC) offers neuroprotective benefits and improves mitochondrial energetics and function.

Objective: This study evaluated the effect of exogenous ALC on physical and mental fatigue, fatigue severity, and physical activity in patients with mild and moderate hepatoencephalopathy (HE1 and HE2, respectively).

Design: A total of 121 patients with overt HE were recruited to the study and were subdivided into 2 groups according to their initial HE grade [HE1 (n = 61) or HE2 (n = 60)]. Thirty-one patients with HE1 and 30 with HE2 received 2 g ALC, and 30 patients with HE1 and 30 patients with HE2 received placebo twice a day for 90 d. All patients underwent clinical and laboratory assessments and automated electroencephalogram analysis.

Results: At the end of the study period, the ALC-treated patients in the HE1 group showed significantly better improvement than did the placebo group in mental fatigue score (-1.7 compared with -0.3; P < 0.05), the fatigue severity scale (-6.4 compared with 2.3; P < 0.001), 7-d Physical Activity Recall questionnaire score (17.1 compared with -2.5; P < 0.001), and Short Physical Performance Battery (2.1 compared with 0.2; P < 0.001); the HE2 group showed significantly better improvement in the fatigue severity scale (-8.1 compared with -5.1; P < 0.001) and 6-min walk test (19.9 compared with 2.3; P < 0.05). Significant decreases in NH(4)(+) were observed in both groups (P < 0.001).

Conclusion: Patients with HE treated with ALC showed a decrease in the severity of both mental and physical fatigue and an increase in physical activity. This trial was registered at clinicaltrials.gov as NCT01223742.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / therapeutic use*
  • Adult
  • Aged
  • Ammonia / blood
  • Double-Blind Method
  • Fatigue / blood
  • Fatigue / drug therapy*
  • Fatigue / etiology
  • Female
  • Hepatic Encephalopathy / blood
  • Hepatic Encephalopathy / complications
  • Hepatic Encephalopathy / drug therapy*
  • Humans
  • Male
  • Memory / drug effects
  • Mental Fatigue / blood
  • Mental Fatigue / drug therapy
  • Mental Fatigue / etiology
  • Middle Aged
  • Physical Endurance / drug effects*
  • Severity of Illness Index
  • Vitamin B Complex / therapeutic use*
  • Walking


  • Vitamin B Complex
  • Acetylcarnitine
  • Ammonia

Associated data

  • ClinicalTrials.gov/NCT01223742