Abstract
OBJECTIVE: This study aimed to compare the relative efficacy of dietary supplements and pharmacological agents in improving metabolic and oxidative stress outcomes in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) through a systematic review and Bayesian network meta-analysis. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched to identify randomized controlled trials (RCTs) published between 1 January 2014, and 3 March 2024, that evaluated the effects of dietary supplements or pharmacological agents on MAFLD. RESULTS: A total of 106 RCTs involving 7,273 participants were included, involving a variety of nutritional and pharmacological interventions. Pharmacological intervention plus bioactive regulator was the most effective in reducing triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C). Nutrient plus pharmacological intervention was the most efficacious in improving glycated hemoglobin (HbA1c) and insulin levels. Pharmacological intervention plus another pharmacological intervention was most effective in reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Phytochemicals significantly reduced interleukin-6 (IL-6), while bioactive metabolic regulators markedly decreased tumor necrosis factor-α (TNF-α). Herbal extracts demonstrated superior effects in enhancing total antioxidant capacity (TAC) and superoxide dismutase (SOD), while oleoylethanolamide (OEA) improved antioxidant enzyme activity and reduced malondialdehyde (MDA) levels. Further analysis revealed that garlic exerted the strongest effect in improving overall antioxidant capacity, whereas L-carnitine showed the most significant efficacy in suppressing lipid peroxidation. CONCLUSION: Multicomponent or mechanistically complementary interventions exhibited more stable potential benefits in improving glucose and lipid metabolism. Bioactive metabolic regulators (L-carnitine), endogenous lipid regulators (OEA), and herbal extracts (garlic) all demonstrated strong efficacy in enhancing antioxidant defense and alleviating oxidative damage. Further high-quality RCTs are needed to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024555065.