S2522 Intermittent Fasting Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Bayesian Network Meta-Analysis

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive hepatic fat accumulation. Intermittent fasting (IF) has emerged as a potential therapeutic strategy, with the ability to induce weight loss, improve insulin sensitivity, and reduce hepatic steatosis. This study aims to compare the efficacy of various IF regimens for managing MASLD. Methods: A systematic review and network meta-analysis of randomized controlled trials (RCTs) investigating different IF regimens for MASLD. PubMed, EMBASE, Web of Science, Scopus, and CENTRAL were searched until April 2025. A Bayesian network meta-analysis was performed in R (version 4.4.3) using pooled mean difference (MD) with 95% credible interval (CrI) relative to the control, based on random or common effects models as determined by the deviance information criterion (DIC), with quantification of the surface under the cumulative ranking (SUCRA). Results: Our analysis included 19 trials comprising 1,149 participants. For liver stiffness, none of the IF regimens had a significant impact, with modified alternate-day fasting (MADF) showing the largest, non-significant reduction (MD: -0.90, 95% Crl: -2.01 to 0.21, SUCRA: 90.84), followed by the 5:2 diet (MD: -0.31, 95% Crl: -0.80 to 0.06, SUCRA: 71.29). For weight change, ADF showed the most significant reduction (MD: -3.27 kg, 95% CrI: -6.32 to -0.11, SUCRA: 77.12). Regarding liver enzymes, only 2 regimens showed a significant reduction: the 5:2 diet: alanine aminotransferase (ALT; MD: -8.68 U/L, 95% CrI: -13.79 to -3.56, SUCRA: 71.27), and aspartate aminotransferase (AST; MD: -4.18 U/L, 95% CrI: -7.32 to -1.04, SUCRA: 81.52); and time-restricted feeding (TRF): ALT (MD: -7.23 U/L, 95% CrI: -10.43 to -4.03, SUCRA: 63.66), and AST (MD: -3.14 U/L, 95% CrI: -5.40 to -0.87, SUCRA: 70.73). None of the assessed regimens affected lipid panel levels and homeostatic model assessment for insulin resistance. Conclusion: MADF and ADF were the most effective interventions for weight loss, with ADF ranking highest. They also showed the greatest reductions in ALT and AST levels, though only ADF achieved significant improvements. The TRF and 5:2 diet contributed to modest, and sometimes significant, metabolic benefits, including reductions in ALT, AST, and LDL cholesterol. Overall, ADF and MADF appear superior for weight management and liver health, while TRF and the 5:2 diet may offer milder metabolic advantages, and none of the regimens affected liver stiffness.