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

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 NH4+ 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. Am J Clin Nutr 2011;93:799-808.