title: Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD) is one of the commonest liver disorders. Obesity, insulin resistance, lipid peroxidation and oxidative stress have been identified amongst the possible hits leading to the onset and progression of this disease. Nutritional evaluation of NAFLD patients showed a lower-than-recommended intake of vitamin E. Vitamin E is a family of 8 isoforms, 4 tocopherols and 4 tocotrienols. Alpha-tocopherol has been widely investigated in liver diseases, whereas no previous clinical trial has investigated tocotrienols for NAFLD. Aim of the study was to determine the effects of mixed tocotrienols, in normalising the hepatic echogenic response in hypercholesterolaemic patients with ultrasound-proven NAFLD.
  
  
  METHODS
  Eighty-seven untreated hypercholesterolaemic adults with ultrasound-proven NAFLD were enrolled and randomised into control group (n = 44) and tocotrienols group (n = 43). The treatment, either mixed tocotrienols 200 mg twice daily or placebo, had a 1-year duration.Normalisation of hepatic echogenic response, being the trial primary aim, was used in sample size calculations. The data were assessed according to intention to treat principle as primary outcome. Per protocol analysis was also carried out as secondary outcome measurement.
  
  
  RESULTS
  Thirty and 34 participants concluded the study in the tocotrienols and placebo group respectively. Alpha-tocopherol levels were within the normal range for all subjects. As primary outcome, the normalisation of hepatic echogenic response was significantly higher for the tocotrienols treated group compared to the placebo group in the intention to treat analysis (P = 0.039; 95% CI = 0.896-6.488). As secondary objective, the per protocol assessment also showed significant rate of remission (P = 0.014; 95% CI = 1.117-9.456). Worsening of NAFLD grade was recorded in two patients in the placebo group, but none in the group treated with tocotrienols. No adverse events were reported for both groups.
  
  
  CONCLUSIONS
  This is the first clinical trial that showed the hepatoprotective effects of mixed palm tocotrienols in hypercholesterolemic adults with NAFLD.
authors.forename: Enrico
authors.initials: E
authors.lastname: Magosso
authors.forename: Mukhtar Alam
authors.initials: MA
authors.lastname: Ansari
authors.forename: Yogheswaran
authors.initials: Y
authors.lastname: Gopalan
authors.forename: Ibrahim Lutfi
authors.initials: IL
authors.lastname: Shuaib
authors.forename: Jia-Woei
authors.initials: JW
authors.lastname: Wong
authors.forename: Nurzalina Abdul Karim
authors.initials: NA
authors.lastname: Khan
authors.forename: Mohamed Rizal
authors.initials: MR
authors.lastname: Abu Bakar
authors.forename: Bee-Hong
authors.initials: BH
authors.lastname: Ng
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia. khyuen@usm.my.
authors.forename: Kah-Hay
authors.initials: KH
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005234:Fatty Liver / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D015596:Nutrition Assessment; D011446:Prospective Studies; D012307:Risk Factors; D024508:Tocotrienols / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D024502:alpha-Tocopherol / Q000008:administration & dosage*; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D024508:Tocotrienols; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D024502:alpha-Tocopherol