The recommended treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) currently focuses on lifestyle changes, including dietary adjustments and increased physical activity. Intermittent fasting is a specific dietary approach in which food intake is restricted for certain periods. Recent scientific evidence suggests that intermittent fasting can positively influence body weight, insulin resistance, and markers of inflammation. This study will examine whether restricting energy intake to approximately 600 kcal on two days per week has beneficial effects on MASLD. The nutritional framework is based on the guidelines of the German Nutrition Society (DGE) for a healthy diet (10 rules for healthy eating). Following a two-week introduction to these DGE recommendations, participants will be randomly assigned to one of two treatment groups. In the intervention group, participants follow a 5:2 intermittent fasting regimen, eating without restrictions on five days per week and limiting intake to about one-quarter of their usual daily energy (≈600 kcal) on two non-consecutive days. In the control group, participants follow a healthy diet according to DGE guidelines without restrictions on timing or energy intake.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
120
Participants in the intervention group follow a 5:2 intermittent fasting regimen, consisting of two non-consecutive days per week with a reduced energy intake of approximately 600 kcal, while on the remaining five days they adhere to a balanced diet in accordance with the recommendations of the German Nutrition Society (DGE).
Department of Internal Medicine II, Saarland University Medical Center, Saarland University,
Homburg, Saarland, Germany
RECRUITINGReduction of controlled attenuation parameter (CAP)
The Controlled Attenuation Parameter (CAP) is a non-invasive ultrasound-based measure obtained during transient elastography (FibroScan®). CAP quantifies the attenuation of ultrasound signals as they pass through the liver, which correlates with the degree of hepatic steatosis. It is expressed in decibels per meter (dB/m). In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), CAP is widely used to assess and grade liver fat content. Higher CAP values reflect greater hepatic fat accumulation. An improvement is defined as a reduction in CAP value of at least 20 dB/m compared to the baseline value
Time frame: from enrollment to the end of treatment at 12 weeks
Improvement in liver stiffness measurment (LSM)
Liver stiffness measurement (LSM) is a non-invasive technique used to assess hepatic fibrosis. It is most commonly performed using transient elastography (FibroScan®), which measures the velocity of a shear wave generated by a mechanical pulse through the liver tissue. The faster the wave propagates, the stiffer the liver, reflecting the degree of fibrosis. Results are expressed in kilopascals (kPa). In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), LSM provides valuable information on fibrosis stage and risk of progression to advanced liver disease, including cirrhosis.
Time frame: from enrollment to the end of treatment at 12 weeks
Improvement in CLDQ-NAFLD/NASH for liver-specific quality of life
The CLDQ (Chronic Liver Disease Questionnaire) is a validated questionnaire for assessing quality of life in patients with chronic liver disease. An improvement in quality of life is defined as a significant improvement in the score on the liver-specific quality of life scale compared to the baseline value.
Time frame: from enrollment to the end of treatment at 12 weeks
Change in insulin sensitivity (HOMA-IR)
Insulin sensitivity is assessed using HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), an index that describes the body's resistance to insulin. An improvement is defined as a significant reduction in the HOMA-IR value compared to the baseline value.
Time frame: from enrollment to the end of treatment at 12 weeks
Changes in the gut microbiome
Changes in the gut microbiome (diversity and composition of the microbial population) are investigated using microbiological analyses (e.g. 16S rRNA sequencing). A change is defined as a significant shift in the composition or diversity of the microbiome compared to the baseline value.
Time frame: from enrollment to the end of treatment at 12 weeks
Reduction of skin AGE
Skin AGE (Advanced Glycation End-products) is measured as a biomarker for oxidative stress and skin ageing. A reduction in Skin AGE is defined as a significant decrease in the AGE value compared to the baseline value.
Time frame: from enrollment to the end of treatment at 12 weeks
Number of participants with selected genetic variants at baseline
Genotyping will be performed at baseline for the following variants: MBOAT7, TM6SF2, PNPLA3, HSD17B13, and MTARC1. The outcome is defined as the number and proportion of participants carrying each genetic variant.
Time frame: baseline
Change in proportion fo circulating immune cell subsets
Immunophenotyping will be performed to quantify circulating immune cell subsets, including Th1, Th17, regulatory T cells (Treg), CD4+ T cells, CD8+ T cells, CD16+ cells, naïve and IgA+ B cells, natural killer cells, neutrophils, and M1 and M2 macrophages. The outcome is defined as the mean change in the proportion (%) of each immune cell subset from baseline to Week 12.
Time frame: from enrollment to the end of treatment at 12 weeks
Change in fasting plasma glucose
Fasting plasma glucose will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12
Time frame: From enrollment to end of treatment at 12 weeks
Change in LDL cholesterol
low-density lipoprotein (LDL) cholesterol will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12.
Time frame: From enrollment to end of treatment at 12 weeks.
Change in HDL cholesterol
High-density lipoprotein (HDL) cholesterol will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12.
Time frame: From enrollment to end of treatment at 12 weeks.
Change in triglycerides
Triglyceride levels will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12.
Time frame: From enrollment to end of treatment at 12 weeks.
Change in blood pressure
Systolic and diastolic blood pressure will be measured in mmHg. The outcome is defined as the mean change from baseline to week 12.
Time frame: From enrollment to end of treatment at 12 weeks.
Change in serum cytokine and chemokine levels
Serum levels of cytokines and chemokines, including IL-6, IL-6 receptor, IL-8, CCL2, TNF-α, and IFN-γ, will be measured. The outcome is defined as the mean change in concentration (pg/mL) from baseline to Week 12.
Time frame: From enrollment to end of treatment at 12 weeks
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