Intermittent Fasting and Metabolic Dysfunction Associated Fatty Liver Disease

NCT06664684 | Completed Results

• 2 other identifiers: MAFLDIF24172
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Intermittent Fasting; Metabolic Dysfunction-Associated Fatty Liver Disease

Keywords

Intermittent fasting; fibroblast growth factor 21; autophagy; fatty liver; time-restricted eating

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Serum Fibroblast Growth Factor-21

  Measurements were taken baseline before and 8 weeks after the intervention.

• Serum Autophagy-Related Protein-5

  Measurements were taken twice baseline and 8 weeks after the intervention.

• Serum Beclin-1

  Measurements were taken twice baseline and 8 weeks after the intervention.

Study Arms (2)

Energy-restricted diet

ACTIVE COMPARATOR

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

Energy + time-restricted diet

EXPERIMENTAL

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

Interventions

Energy-restricted dietary intervention OTHER

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.

Energy-restricted diet

Energy + time-restricted dietary intervention OTHER

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.

Energy + time-restricted diet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istanbul Bilgi University: lead
• Marmara University: collaborator

Study Sites (1)

Institute of Gastroenterology, Liver Research Unit, Marmara University

Istanbul, 34854, Turkey (Türkiye)

Location

Related Publications (6)

• 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.

  PMID: 26725058 RESULT

• 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.

  PMID: 25071723 RESULT

• 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.

  PMID: 32690662 RESULT

• 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.

  PMID: 32042044 RESULT

• 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.

  PMID: 32674529 RESULT

• 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.

  PMID: 32044314 RESULT

MeSH Terms

Conditions

Intermittent Fasting; Fatty Liver

Condition Hierarchy (Ancestors)

Fasting; Feeding Behavior; Behavior; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Dr. Tugce Ozlu Karahan
• Organization: İstanbul Bilgi University

tugce.karahan@bilgi.edu.tr

+90 212 311 5042

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 24, 2024
• First Posted: October 29, 2024
• Study Start: May 23, 2022
• Primary Completion: January 30, 2023
• Study Completion: September 12, 2023
• Last Updated: June 26, 2025
• Results First Posted: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)