Hepato-Protective Effects of Delta-Tocotrienol and Alpha-Tocopherol in Patients with Non-Alcoholic Fatty Liver Disease: Regulation of Circulating MicroRNA Expression

Int J Mol Sci. 2022 Dec 21;24(1):79. doi: 10.3390/ijms24010079.


MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 (n = 50) 300 mg or αTF (n = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis.

Keywords: apoptosis; circulating microRNAs; inflammation; non-alcoholic fatty liver disease; α-tocopherol; δ-tocotrienol.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Biomarkers / metabolism
  • Circulating MicroRNA* / metabolism
  • Humans
  • Inflammation / metabolism
  • Insulin Resistance*
  • Liver / metabolism
  • MicroRNAs* / metabolism
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Non-alcoholic Fatty Liver Disease* / genetics
  • alpha-Tocopherol / metabolism
  • alpha-Tocopherol / pharmacology


  • Circulating MicroRNA
  • alpha-Tocopherol
  • tocotrienol, delta
  • MicroRNAs
  • Biomarkers
  • MIRN122 microRNA, human