The Effects of Combined Vitamin E and C for Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD): A Systematic Review and Meta-Analysis of Randomized Controlled Trials

OBJECTIVE: Antioxidant therapy is a promising treatment option for non-alcoholic fatty liver disease (NAFLD) after failure of lifestyle modification. We aimed to explore the efficacy of combined vitamin E and C therapy compared to no treatment for NAFLD. METHODS: A literature search was performed in Ovid Embase, Ovid Medline, PubMed, Cochrane Library, Scopus, and Web of Science from inception to 28(th) April 2020. A systematic review and meta-analysis were conducted on randomized controlled trials that assessed vitamin E and C co-treatment in NAFLD. Quality of evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Assessed outcomes were changes in imaging findings, histological features, and serum transaminases. Subgroup analyses that compared adult versus children were further explored. RESULTS: Four studies (n=260) satisfied our eligibility criteria. Vitamin co-treatment did not improve ultrasonographic liver brightness, histological parameters of hepatocyte injury (steatosis, lobular inflammation, and ballooning), fibrosis grading (standardized mean difference [SMD ]: 0.02, 95% CI: -0.40 to 0.45, I(2)=13%), serum aspartate transaminase (mean difference [MD]: -0.05, 95% CI: -2.59 to 2.50, I(2)=0%), and serum alanine transaminase (MD: 2.82, 95% CI: -2.11 to 7.76, I(2)=57%). Subgroup stratifications illustrated similar findings. CONCLUSION: Vitamin co-treatment may have limited efficacy in NAFLD. However, we have little confidence in our effect estimates due to bias and other major constraints.