Effects of Mediterranean diet, exercise, and their combination on body composition and liver outcomes in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials.

• Lifestyle interventions remain essential in preventing and managing liver fat accumulation.

• Consistent adherence to dietary patterns and exercise protocols offers measurable metabolic and hepatic benefits.

• The MD and aerobic exercise may improve weight and liver health in people with MASLD/MASH.

Introduction
This study aimed to assess the effect of the Mediterranean diet (MD), exercise, and their combination on anthropometric and liver outcomes in patients with metabolic dysfunction-associated steatotic liver disease / metabolic dysfunction-associated steatohepatitis (MASLD/MASH).

Methods
This was a systematic review and meta-analysis of thirty-seven randomised controlled trials. Among the included articles eleven assessed the MD, twenty-seven assessed exercise, and two assessed the combination of the MD and exercise.

Results
In comparison to control groups:

A. MD alone:

• Weight: Significant reduction (WMD = −2.38 kg; 95% CI −4.11 to −0.66; P = 0.01).

• Body mass index: Significant decrease (WMD = −0.70 kg/m²; 95% CI −1.03 to −0.36; P < 0.001).

• Waist Circumference: Notable reduction (WMD = −1.56 cm; 95% CI −3.02 to −0.09; P = 0.04)

• Liver Enzymes: Alanine transaminase (ALT) was significantly reduced (WMD = −3.96 IU/L; 95% CI −6.54 to −1.38; P < 0.001). No significant changes on aspartate transaminase (AST) (WMD = −2.14 IU/L; 95% CI −5.63 to 1.34; P = 0.23) or gamma-glutamyl transferase (GGT) (WMD = −3.55 IU/L; 95% CI −11.57 to 4.47; P = 0.39).

• Liver fat and fibrosis: The majority of RCTs reported significant improvements in fatty liver index, liver steatosis, and fibrosis outcomes compared to control or low-fat diets.

B. Exercise interventions:

• Weight: Aerobic (WMD = −1.56 kg; 95% CI −2.31 to −0.82; P < 0.001; Power > 85%) and combined aerobic-resistance (WMD = −1.90 kg; 95% CI −3.59 to −0.22; P = 0.03) both effective.

• Liver enzymes: Resistance exercise significantly reduced ALT (WMD = −15.40 IU/L; 95% CI −28.60 to −2.20; P < 0.001); AST or GGT remained unchanged.

• Liver fat: Aerobic and combined exercise consistently decreased intrahepatic fat; resistance training effects were variable.

• Fibrosis: Mostly unchanged, except high-intensity interval training showing a significant NFS reduction (P < 0.05).

C. Combined MD + Exercise:

• Both interventions improved intrahepatic fat, though group differences were not statistically significant.

Conclusion

The authors concluded that MD and aerobic exercise independently contribute to significant weight reduction and improvements in hepatic function among patients with MASLD/MASH

• Future high-quality, large-scale RCTs employing standardised definitions of the MD, harmonised intervention protocols, and extended follow-up periods are needed to better determine the effects of lifestyle interventions on body composition and liver outcomes in MASLD.

• Longer-term studies are needed to determine the sustainability of MD and exercise-induced improvements in hepatic steatosis and fibrosis.

• Standardisation of liver outcome measures may enhance data comparability across trials.

• Investigations into behavioural and adherence factors influencing the effectiveness of lifestyle interventions could inform tailored, patient-centred strategies.