Intermittent Fasting and Metabolic Dysfunction Associated Fatty Liver Disease

Effects of Intermittent Fasting in Metabolic Dysfunction Associated Fatty Liver Disease

Previous studies have investigated the effect of different dietary patterns on metabolic dysfunction-associated fatty liver disease (MAFLD), for which lifestyle modification remains the primary treatment. The present study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers including autophagy-related protein (ATG)-5 and BECLIN-1 levels, as well as on hepatic steatosis and fibrosis levels in overweight or obese patients with MAFLD to elucidate the efficacy of intermittent fasting in the management of MAFLD. The study included 48 patients diagnosed with MAFLD. Patients were randomly assigned into two groups: 22 received a dietary treatment involving 22-25 kcal/kg/day of energy for 8 weeks (energy-restricted diet group), and 26 followed the same dietary intervention and a 16:8 pattern (energy + time-restricted diet group). The patients were assessed for various parameters at baseline (T0) and at the end of the week 8 (T8). The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan® device. Serum levels of FGF-21, BECLIN-1, and ATG-5 were determined using enzyme-linked immunosorbent assay.

Study Overview

• Status: Completed
• Conditions: Intermittent Fasting; Metabolic Dysfunction-Associated Fatty Liver Disease
• Intervention / Treatment: Other: Energy-restricted dietary intervention; Other: Energy + time-restricted dietary intervention

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34854
    • Institute of Gastroenterology, Liver Research Unit, Marmara University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Diagnosed with MAFLD
• Aged 18-65 years
• BMI ≥ 25 kg/m²
• A stable body weight (<5 kg weight loss or gain) over the last 3 months preceding the start of the study
• Signed the informed consent form.

Exclusion Criteria:

• An average daily alcohol consumption >20 g for females and >30 g for males
• Pregnant or lactating women
• Patients with ischemic heart disease or heart failure, chronic inflammatory diseases, chronic viral infections, cancer, moderate-to-severe kidney disease, uncontrolled hypertension, and eating disorders
• Those with a history of bariatric surgery
• Those on insulin due to increased risk of hypoglycemia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Energy-restricted diet; The energy-restricted diet group followed an 8-week long dietary treatment involving 22-25 kcal/kg/day based on ideal body weight.	Other: Energy-restricted dietary intervention; The diets were planned based on current guidelines, manuals, systematic reviews, and meta-analyses published in recent years on MAFLD [5-6, 27-28]. In this diet, carbohydrates constituted 50%-55% of total energy intake, proteins constituted 10%-20%, and fats constituted 25%-35%. The content of the diets was tailored to each patient, considering various factors such as sex, age, and physical activity status.
Experimental: Energy + time-restricted diet; Patients in the energy + time-restricted diet group followed the same dietary intervention and a 16:8 eating pattern where they were instructed to restrict their energy intake to an 8-h time window and not to consume energy-containing foods or drinks during the remaining 16 h.	Other: Energy + time-restricted dietary intervention; Patients in the energy + time-restricted diet group followed the same dietary intervention and a 16:8 eating pattern where they were instructed to restrict their energy intake to an 8-h time window and not to consume energy-containing foods or drinks during the remaining 16 h. Participants were allowed to consume energy-free beverages such as water, coffee, and tea during fasting. The timing of the eating window during the day varied according to participants' lifestyles and habits. However, considering the importance of nocturnal fasting, the eating window in all patients started at 10:00-12:00 in the day and ended at 18:00-20:00 in the evening. The energy-restricted diet group did not follow any time restriction in the planning of main meals and snacks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transient Elastography-Controlled Attenuation Parameter	The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan® device. All FibroScan measurements were performed following the manufacturer's instructions as specified previously. Hepatic steatosis was defined using controlled attenuation parameter (CAP). The CAP measurement, which indicates steatosis, ranged between 100 and 400 dB/m.	Measurements were taken twice baseline and 8 weeks after the intervention.
Transient Elastography-Liver Stiffness Measurement	The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan® device. All FibroScan measurements were performed following the manufacturer's instructions as specified previously. The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan® device. All FibroScan measurements were performed following the manufacturer's instructions as specified previously. Hepatic fibrosis were defined using liver stiffness measurement (LSM). LSM measurement ranged between 2.5 and 75 kPa.	Measurements were taken twice baseline and 8 weeks after the intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Fibroblast Growth Factor-21	At each time point (baseline and week 8), one serum sample was collected per participant. Serum Fibroblast Growth Factor-21 (FGF-21) levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits, following the manufacturer's protocols (Human FGF-21 ELISA, Biovendor, Czech Republic).	Measurements were taken baseline before and 8 weeks after the intervention.
Serum Autophagy-Related Protein-5	At each time point (baseline and week 8), one serum sample was collected per participant. Serum autophagy-related protein-5 (ATG-5) were analyzed using enzyme-linked immunosorbent assay (ELISA) kits, following the manufacturer's protocols (Human Autophagy protein 5 [ATG5] ELISA Kit, MyBioSource, Inc. USA).	Measurements were taken twice baseline and 8 weeks after the intervention.
Serum Beclin-1	At each time point (baseline and week 8), one serum sample was collected per participant. Serum Beclin-1 were analyzed using enzyme-linked immunosorbent assay (ELISA) kits, following the manufacturer's protocols (Human BECN1 [Beclin 1] ELISA Kit, ElabScience, USA).	Measurements were taken twice baseline and 8 weeks after the intervention.

Collaborators and Investigators

• Sponsor: Istanbul Bilgi University
• Collaborators: Marmara University

Publications and helpful links

General Publications

• Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020 May;158(7):1999-2014.e1. doi: 10.1053/j.gastro.2019.11.312. Epub 2020 Feb 8.
• Czaja MJ. Function of Autophagy in Nonalcoholic Fatty Liver Disease. Dig Dis Sci. 2016 May;61(5):1304-13. doi: 10.1007/s10620-015-4025-x. Epub 2016 Jan 2.
• Itoh N. FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases. Front Endocrinol (Lausanne). 2014 Jul 7;5:107. doi: 10.3389/fendo.2014.00107. eCollection 2014.
• Kleinert M, Muller TD. A New FGF21 Analog for the Treatment of Fatty Liver Disease. Diabetes. 2020 Aug;69(8):1605-1607. doi: 10.2337/dbi20-0025. No abstract available.
• Byun S, Seok S, Kim YC, Zhang Y, Yau P, Iwamori N, Xu HE, Ma J, Kemper B, Kemper JK. Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase. Nat Commun. 2020 Feb 10;11(1):807. doi: 10.1038/s41467-020-14384-z.
• Hydes TJ, Ravi S, Loomba R, E Gray M. Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH. Clin Mol Hepatol. 2020 Oct;26(4):383-400. doi: 10.3350/cmh.2020.0067. Epub 2020 Jul 17.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2022
• Primary Completion (Actual): January 30, 2023
• Study Completion (Actual): September 12, 2023

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 28, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: fatty liver; autophagy; Intermittent fasting; time-restricted eating; fibroblast growth factor 21
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: MAFLDIF; 24172 (Health Institutes of Türkiye (TUSEB))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No