Intermittent fasting strategies for metabolic dysfunction-associated steatotic liver disease: A systematic review and frequentist network meta-analysis of randomized controlled trials.

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition globally. Lifestyle modification through continuous calorie restriction is the cornerstone of management, but long-term adherence is a significant challenge. Intermittent fasting (IF) has been proposed as a more sustainable alternative, though evidence comparing the efficacy of different IF regimens remains limited. This study aimed to compare the effects of various IF strategies on liver and metabolic outcomes in patients with MASLD.

METHODS

A systematic review and network meta-analysis of randomized controlled trials (RCTs) was conducted by searching PubMed, EMBASE, Web of Science, Scopus, and CENTRAL to April 2025. We included RCTs that compared different IF regimens-including time-restricted feeding (TRF), alternate-day fasting (ADF), and the 5:2 Diet-among themselves or with non-IF controls in adults with MASLD. A frequentist network meta-analysis was performed, and continuous outcomes were analyzed using mean difference (MD) with 95% confidence intervals (CIs). PROSPERO registration ID: CRD420251068065.

RESULTS

Nineteen RCTs involving 1149 participants were included in the analysis. TRF was the most effective regimen for reducing hepatic steatosis (MD: -23.32 dB/m), followed by the 5:2 Diet; however, none of the IF regimens significantly improved liver stiffness. ADF demonstrated the greatest reductions in body weight, waist circumference, and body fat, and was the only regimen to improve insulin resistance (HOMA-IR) significantly. Both the 5:2 Diet and TRF significantly reduced ALT and AST levels. Additionally, the 5:2 Diet led to a modest but significant reduction in LDL-C.

CONCLUSION

IF effectively improves hepatic steatosis and key metabolic risk factors in patients with MASLD, but does not affect liver stiffness. The optimal IF strategy may be tailored to patient-specific goals: TRF is superior for reducing liver fat, ADF is most effective for improving adiposity and insulin resistance, and the 5:2 Diet may offer a modest benefit for LDL-C reduction.