Intermittent Fasting and Metabolic Dysfunction Associated Fatty Liver Disease

Effects of Intermittent Fasting in Metabolic Dysfunction Associated Fatty Liver Disease

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06664684

Enrollment

Registered

2024-10-29

Start date

2022-05-23

Completion date

2023-09-12

Last updated

2025-06-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Intermittent Fasting, Metabolic Dysfunction-Associated Fatty Liver Disease

Keywords

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

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.

Interventions

OTHEREnergy-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.

OTHEREnergy + 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Transient Elastography-Controlled Attenuation Parameter	Measurements were taken twice baseline and 8 weeks after the intervention.	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.
Transient Elastography-Liver Stiffness Measurement	Measurements were taken twice baseline and 8 weeks after the intervention.	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.

Secondary

Measure	Time frame	Description
Serum Fibroblast Growth Factor-21	Measurements were taken baseline before and 8 weeks after the intervention.	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).
Serum Autophagy-Related Protein-5	Measurements were taken twice baseline and 8 weeks after the intervention.	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).
Serum Beclin-1	Measurements were taken twice baseline and 8 weeks after the intervention.	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).

Countries

Turkey (Türkiye)

Participant flow

Participants by arm

Arm	Count
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. 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.	22
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. 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.	26
Total	48

Baseline characteristics

Characteristic	Energy + Time-restricted Diet	Total	Energy-restricted Diet
Age, Continuous	46.0 years	49.0 years	51.0 years
Race/Ethnicity, Customized Turkish	26 Participants	48 Participants	22 Participants
Region of Enrollment Turkey	26 participants	48 participants	22 participants
Sex: Female, Male Female	15 Participants	27 Participants	12 Participants
Sex: Female, Male Male	11 Participants	21 Participants	10 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 22	0 / 26
other Total, other adverse events	0 / 22	0 / 26
serious Total, serious adverse events	0 / 22	0 / 26

Outcome results

Primary

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.

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