Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial.

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. CONCLUSION: This is the first clinical trial that showed the hepatoprotective effects of mixed palm tocotrienols in hypercholesterolemic adults with NAFLD.

Prevalence of non-alcoholic fatty liver in a hypercholesterolemic population of northwestern peninsular Malaysia.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and a frequent finding on ultrasound examination. NAFLD is considered as the liver component of metabolic syndrome and is linked to accelerated atherosclerosis and cardiovascular disease. No data from systematic studies regarding the prevalence of NAFLD are available for the Malaysian population. One hundred eighty untreated hypercholesterolemic volunteers underwent blood and ultrasound examinations to evaluate their livers. NAFLD was diagnosed in 102 subjects (56.7%) with similar prevalences between sexes. Of the 102 positive subjects 82 (80.4%) were graded as mild, 17 (16.7%) as moderate and 3 (2.9%) as severe fatty liver cases. Elevated fasting plasma glucose (FPG) levels were found in 13 of 180 subjects (7.2%), while elevated AST and ALT levels were seen in 30 (16.7%) and 22 (12.2%) of the180 subjects, respectively.