Effects of ketogenic diet on non-alcoholic fatty liver disease–a systematic review and meta-analysis

Non-Alcoholic Fatty Liver Disease (NAFLD) is a prevalent global metabolic disorder linked to obesity, insulin resistance, and dyslipidemia, burdening public health. With limited therapeutic strategies, dietary interventions like the Very-Low-Calorie Ketogenic Diet (VLCKD, high fat, very low carbohydrate, adequate protein) show metabolic improvement potential, but its comprehensive effects on NAFLD remain insufficiently validated. This study systematically evaluated VLCKD’s effects on NAFLD-related indices to clarify its therapeutic value. An RCT-based meta-analysis searched EMBASE, Web of Science, PubMed, and Cochrane databases. Eligible RCTs included adults with NAFLD (imaging/histology confirmation), comparing VLCKD with conventional diets. Outcomes included hepatic function (ALT, AST), body composition (BMI, weight), and glycemic/insulin indices (glucose, HOMA-IR, insulin). Heterogeneity was assessed via I²; fixed/random-effects models and subgroup analyses addressed biases. Twelve RCTs (854 patients) showed VLCKD significantly reduced ALT (SMD=-0.29, 95%CI[-0.45,-0.13], P = 0.0004, I²=0%), AST (SMD=-0.18, 95%CI[-0.34,-0.02], P = 0.03, I²=37%), BMI (SMD=-0.81, P < 0.00001, I²=84%), weight (SMD=-1.08, P < 0.00001, I²=89%), glucose (SMD=-0.46, P = 0.006, I²=73%), insulin (SMD=-0.75, P < 0.00001, I²=62%), and HOMA-IR (SMD=-0.87, P = 0.002, I²=87%). Sensitivity/subgroup analyses addressed heterogeneity; publication bias was minimal. VLCKD effectively improves hepatic function, reduces weight, and alleviates insulin resistance in NAFLD, serving as a feasible non-pharmacological intervention to reduce NAFLD progression and public health burden. Larger, long-term RCTs are needed to optimize VLCKD formulation and personalized application. CRD420250635846