Effects of Intermittent Fasting on Liver Steatosis and Fibrosis, Serum FGF-21 and Autophagy Markers in Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial

Background: This randomized controlled study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers, as well as on hepatic steatosis and fibrosis levels in overweight or obese patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: Patients were randomly assigned into two groups: received a dietary treatment involving 22-25 kcal/kg/day of energy for 8 weeks and followed the same dietary intervention and a 16:8 pattern. The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan (R) device. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), determined by transient elastography, reflect hepatic steatosis and fibrosis, respectively. In duplicate, serum levels of FGF-21, Beclin-1, and ATG-5 were determined using enzyme-linked immunosorbent assay. Results: The study included 48 patients with a mean age of 48.2 +/- 1.4 years (27 female and 21 male). Improvements in anthropometric measurement and CAP and LSM levels and a decrease in serum FGF-21 levels were found in both groups (p < 0.05). Changes in the CAP and FGF-21 levels were higher in the energy + time-restricted diet group (p < 0.05). Autophagy-related protein (ATG)-5 levels increased only in the energy + time-restricted diet group [(0.74 (0.46-1.29) ng/mL vs. 0.95 (0.73-1.32) ng/mL, p = 0.03]. Conclusions: Intermittent fasting was potentially practical in the management of MAFLD. In particular, changes in FGF-21 and ATG-5 levels indicate the potential of intermittent fasting to regulate metabolic processes and autophagy. However, methodological limitations should be taken into consideration when interpreting the study results.