Comparison of delta-tocotrienol and alpha-tocopherol effects on hepatic steatosis and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: A randomized double-blind active-controlled trial

Complement Ther Med. 2022 Nov:70:102866. doi: 10.1016/j.ctim.2022.102866. Epub 2022 Aug 3.


Objective: We aimed to compare the efficacy of δ-tocotrienol with α-tocopherol in the treatment of patients with non-alcoholic fatty liver disease (NAFLD).

Design and interventions: This study was a double-blinded, active-controlled trial. The patients with NAFLD were randomly assigned to receive either δ-tocotrienol 300 mg or α-tocopherol 268 mg twice daily for 48 weeks.

Endpoints: The primary endpoints were change from baseline in fatty liver index (FLI), liver-to-spleen attenuation ratio (L/S ratio), and homeostatic model assessment for insulin resistance (HOMA-IR) at 48 weeks. Key secondary endpoints were change in markers of inflammation, oxidative stress, and hepatocyte apoptosis. Clinical assessment, biochemical analysis, and computed tomography scan of the liver were conducted at baseline, 24 and 48 weeks.

Results: A total of 100 patients (δ-tocotrienol = 50, α-tocopherol = 50) were randomized and included in the intention to treat analysis. Compared with baseline, there was a significant improvement (p < .001) in FLI, L/S ratio, HOMA-IR, and serum malondialdehyde in both groups at 48 weeks that was not significant between the two groups. However, there was a significantly greater decrease in body weight, serum interleukin-6, tumor necrosis factor-alpha, leptin, cytokeratin-18, and increase in adiponectin in the δ-tocotrienol group compared to the α-tocopherol group at 48 weeks (p < .05). No adverse events were reported.

Conclusion: δ-tocotrienol and α-tocopherol exerted equally beneficial effects in terms of improvement in hepatic steatosis, oxidative stress, and insulin resistance in patients with NAFLD. However, δ-tocotrienol was more potent than α-tocopherol in reducing body weight, inflammation, and apoptosis associated with NAFLD. TRIAL REGISTRATION: Sri Lankan Clinical Trials Registry (

Keywords: Fatty liver index; Inflammatory biomarkers; Liver-to-spleen attenuation ratio; Non-alcoholic fatty liver disease; α-tocopherol; δ-tocotrienol.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Biomarkers
  • Body Weight
  • Double-Blind Method
  • Humans
  • Inflammation
  • Insulin Resistance*
  • Liver
  • Non-alcoholic Fatty Liver Disease*
  • Vitamin E / analogs & derivatives
  • alpha-Tocopherol


  • Biomarkers
  • Vitamin E
  • tocotrienol, delta
  • alpha-Tocopherol