title: Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study.
abstract: 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).
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological Chemistry, Medical Chemistry, and Molecular Biology, University of Catania, Italy. m.malaguarnera@email.it
authors.forename: Michele
authors.initials: M
authors.lastname: Malaguarnera
authors.forename: Marco
authors.initials: M
authors.lastname: Vacante
authors.forename: Maria
authors.initials: M
authors.lastname: Giordano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pennisi
authors.forename: Rita
authors.initials: R
authors.lastname: Bella
authors.forename: Liborio
authors.initials: L
authors.lastname: Rampello
authors.forename: Mariano
authors.initials: M
authors.lastname: Malaguarnera
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
mesh_terms: D000108:Acetylcarnitine / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000641:Ammonia / Q000097:blood; D004311:Double-Blind Method; D005221:Fatigue / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D005222:Mental Fatigue / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D008875:Middle Aged; D010807:Physical Endurance / Q000187:drug effects*; D012720:Severity of Illness Index; D014803:Vitamin B Complex / Q000627:therapeutic use*; D016138:Walking
chemical_list: D014803:Vitamin B Complex; D000108:Acetylcarnitine; D000641:Ammonia