The efficacy of vitamin E in reducing non-alcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population. Clinical trials have questioned the role of vitamin E in the treatment of NAFLD with or without other interventions, with still no firm conclusion reached. This study aims to examine the efficiency of vitamin E alone or combined in the management of NAFLD.

Methods: We performed a systematic literature search on PubMed, Scopus, Embase, Ovid, EBSCO host, Science Direct, Web of Science, and Cochrane CENTRAL for randomized controlled trials (RCTs) of the role of vitamin E alone or combined in NAFLD patients. Extracted manuscripts reported data on biochemical, histological, anthropometric, and metabolic outcomes. Baseline characteristics, settings, dosage, and frequency were also collected.

Research: A total of 1317 patients from 15 RCTs were included in our systematic review and meta-analysis. Vitamin E was superior at improving alanine aminotransferase (ALT), aspartate aminotransferase (AST), NAFLD activity score (NAS), and fibrosis in short- and long-term follow up in the adult population, and long-term follow up in the pediatric population. Improvements in metabolic outcomes were best noticed in pediatric patients. Results from multiple regression models showed a significant association between ALT-AST levels and vitamin E dose. AST levels had a significant effect on NAS, and patients with a baseline AST > 50 IU/l showed more promising results. Changes in weight and body mass index (BMI) were strongly associated with changes in NAS.

Conclusion: Current evidence affirms that vitamin E - whether alone or combined - improves biochemical and histological outcomes in adults and pediatric patients.

Keywords: NAFLD; NASH; meta-analysis; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; vitamin E.

Figure 1.

(A) PRISMA flow diagram illustrates the search strategy, screening and the selection process. (B) Risk of bias graph according to Cochrane risk of bias assessment tool. PRISMA, preferred reporting items for systematic reviews and meta-analyses; RCT, randomized controlled trial.

Figure 2.

The overall meta-regression mean difference of the interaction between dose/age on x-axis and ALT/AST on y-axis. (E–H) The overall meta-regression mean difference of the interaction between age/sex on x-axis and Fibrosis/NAS on y-axis. (I–Q) The overall meta-regression mean difference of the interaction between ALT/AST/BMI/weight on x-axis and Fibrosis/NAS on y-axis. (R–U) The overall meta-regression mean difference of the interaction between co-interventions on x-axis and ALT/AST/Fibrosis/NAS on y-axis. The stars indicates significant predictions. (V–Y) Funnel plots of ALT/AST/Fibrosis/NAS showing no evidence of publication bias. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score.

Figure 3.

Forest plots show the MD in each outcome along with the associated 95% CI in the two arms at 3, 6, 12, 18, and 24 months; p indicates pediatric population. Outcomes: (A) ALT, (B) AST, (C) fibrosis, (D) NAS, (E) BMI, (F) weight, (G) waist-circumference, (H) FBG, (I) FBI, (J) HOMA-IR, (K) total-cholesterol, (L) triglycerides, (M) to HDL, (N) LDL. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CI, confidence interval; FBG, fasting blood glucose; FBI, fasting blood insulin; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; LDL, low-density lipoprotein; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score.