Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common health challenge worldwide and urgently requires effective therapeutic interventions. Flavonoids, a diverse group of plant-derived polyphenols, have demonstrated multifaceted biological functions, like anti-inflammatory, antioxidant and metabolic regulatory capacities, suggesting their potential utility in the management of NAFLD. OBJECTIVE: This systematic review and meta-analysis aims to synthesize evidence from randomized controlled trials (RCTs) that examined the effects of flavonoid supplementation (including specific subclasses) in patients with NAFLD on liver function, markers of inflammation, lipid profiles, anthropometric measures and insulin resistance. METHODS: This study rigorously adhered to the Cochrane Handbook for Systematic Reviews of Interventions (Version 6.5, 2024) and the PRISMA guidelines. A substantial literature review was obtained from PubMed, OVID, Web of Science Core Collection, Embase, and Cochrane Library databases, including studies published through December 2024. RESULTS: The analysis incorporated 25 RCTs involving 1,689 participants with NAFLD. Flavonoids intervention significantly decreased aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), total cholesterol (TC), steatosis score, body mass index (BMI), triglycerides (TG), fasting blood sugar (FBS), insulin levels and augmented the quantitative insulin sensitivity check index (QUICKI) levels. However, no significant alterations were observed in gamma-glutamyl transferase (GGT), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), body weight (WT), waist-to-height ratio (WHtR), hip circumference (HC), Waist Circumference (WC). Moreover, the impact on hepatic steatosis and fibrosis scores was non-significant. CONCLUSION: Flavonoids exhibit potential therapeutic benefits in mitigating liver enzyme levels, lipid profiles, enhancing insulin sensitivity among NAFLD patients. Nonetheless, their influence on inflammatory markers, and fibrosis scores appears to be limited. Future investigations should focus on assessing the long-term security and effectiveness of flavonoid supplementation in managing NAFLD and exploring their synergistic potential in combination with other therapeutic strategies. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251001203.