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

Abstract

BackgroundNonalcoholic 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.MethodsEighty-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.ResultsThirty 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.ConclusionThis is the first clinical trial that showed the hepatoprotective effects of mixed palm tocotrienols in hypercholesterolemic adults with NAFLD.Trial registrationClinicaltrials.gov, NCT00753532.

Tocotrienols induce endoplasmic reticulum stress and apoptosis in cervical cancer cells

“…More recently, the beneficial effects of T3 on different human disorders have been evaluated in clinical trials [1, 33, 42, 45]. Within this context, few studies have definitively addressed the molecular mechanisms underlying T3 activity.…”

Gamma‐Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice

“…γT3 has been shown to reduce the triglyceride (TG) accumulation in rat primary hepatocytes and a rat model of NAFLD . Convincing evidence was also from the pilot intervention study with NASH patients, demonstrating that mixed isomers of tocotrienol (T3) delay the progression of end‐stage liver diseases . These studies suggest a translational potential of γT3 as a therapeutic dietary molecule treating NAFLD, while the underlying mechanisms are largely undetermined.…”

Biological Properties of Tocotrienols: Evidence in Human Studies

“…After supplementation of 400 mg of TRF for a year, patients in the tocotrienol arm showed significant improvement in normalization of hepatic echogenic response in addition to absence of worsening of NAFLD grade [39]. On the other hand, two patients in the placebo arm were reported to show disease progression with worsening grade.…”