The goal of this clinical trial is to learn if daily supplementation with Low-methoxy (LM) pectin (polysaccharides extracted from citrus peels), which are commonly found in the UK diet (not pharmacological agents), can reduce systemic inflammation and improve gut microbiota composition in adults recently diagnosed with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The main question it aims to answer is: -How does dietary Low-methoxy (LM) pectin supplementation affect systematic inflammation pathways such as those mediated by gut microbiota composition and what are the impacts on general metabolic indicators in individuals with MASLD? Researchers will compare a group taking 15g of LM-pectin with 10g of cocoa powder to a placebo group receiving 10g of placebo with 10g of cocoa powder to see if LM-pectin has measurable effects on inflammation and gut microbiota. Participants will: * Take a daily supplement for 6 weeks: either 15g of LM-pectin with 10g of cocoa powder (intervention), or 10g of placebo with 10g of cocoa powder (control) * Provide stool and fasting blood samples before and after the intervention * Undergo anthropometric measurements (weight, height, waist/hip ratio, and blood pressure) * Complete a case report form (CRF) including demographics and health/medical history * Undergo a FibroScan™ to assess liver health * (Optional) Participate in MRI scans to evaluate gut permeability
Primary Objective: This research aims to study the effects of daily ingestion of LM pectin on inflammation pathways by measuring the blood inflammatory markers associated with physiological processes (TNFα, IL-6, IL-10, IFNᵞ, C - reactive protein, Zonulin (Haptoglobulin), IL-1β). Secondary Objectives: 1. Assessment of changes in anthropometric measures. 2. Assessment of changes in general metabolic indicators, such as fasting blood glucose and other blood-based markers relevant to MASLD (e.g., CK18-M30, CK18-M65, PROC3, Enhanced Liver Fibrosis (ELF), NIS2+™, YKL-40, microRNA miR-34a-5p, liver-associated enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline Phosphatase (ALP)), bilirubin levels, lipid profiles, and platelet counts. 3. Exploration of changes in gut microbiome composition. 4. Exploration of modifications in non-invasive physiological assessments linked to liver characteristics, such as fat content and stiffness through controlled attenuation parameter (CAP) and transient elastography. 5. Observation of alteration in fat in liver and other surrounding abdominal organs through Dixon MRI sequence in patients who will agree to have 2 MRI scans. 6. Validation of MRI measures (T2\*) as a tool to measure gut permeability among MASLD patients and investigation of changes in gut permeability in participants undergoing two MRI scans. 7. Investigation the presence of gene variants such as MUC2, encoding Mucin protein, that are associated with gut permeability.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
45
15g of pectin with 10g of cocoa powder added as flavour were randomly allocated to eligible participants.
10g of cocoa powder served as the control/ placebo to compare the effects observed with pectin.
To validate MRI scans as a tool to assess intestinal wall thickness to indicate gut permeability on MASLD patients, the investigators will scan 15 healthy volunteers twice, at baseline and after 6 weeks, and then compare their results with MASLD participant results at baseline and after 6 weeks.
Sir Peter Mansfield Imaging Centre, University of Nottingham
Nottingham, United Kingdom
RECRUITINGNottingham Clinical Research Facility at Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
RECRUITINGUniversity of Nottingham
Nottingham, United Kingdom
RECRUITINGQuantification of blood markers contributing to systemic inflammation pathway (TNFα (pg/mL), IL-6 (pg/mL), IL-10 (pg/mL), IFNᵞ (pg/mL), C-Reactive Protein (pg/mL), Zonulin (Haptoglobulin)(pg/m), IL-1β(pg/mL)).
Change in circulating markers of inflammation measured by ELISAs in serum samples collected pre and post the 6-weeks intervention period.
Time frame: 6 weeks
Change in BMI (kg/m²)
Changes in BMI pre and post the 6-weeks intervention period.
Time frame: 6 weeks
Assessment of changes in general metabolic indicators, such as fasting blood glucose and other blood-based markers relevant to MASLD (e.g., CK18-M30, CK18-M65, PROC3, Enhanced Liver Fibrosis (ELF), NIS2+™, YKL-40, microRNA miR-34a-5p)
Changes in general metabolic indicators, such as fasting blood glucose and other blood-based markers relevant to MASLD (e.g., CK18-M30, CK18-M65, PROC3, Enhanced Liver Fibrosis (ELF), NIS2+™, YKL-40, microRNA miR-34a-5p) pre and post the 6-weeks intervention period.
Time frame: 6 weeks
Assessment of changes in liver-associated enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline Phosphatase (ALP)), bilirubin levels, lipid profiles, and platelet counts.
Changes in liver-associated enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline Phosphatase (ALP)), bilirubin levels, lipid profiles, and platelet counts pre and post the 6-weeks intervention period.
Time frame: 6 weeks
Change in Liver Stiffness via Transient Elastography
CAP and liver stiffness (in kPa) measured using transient elastography.
Time frame: 6 weeks
Change in Liver Fat Fraction Assessed by Dixon MRI Sequence.
Fat fraction (%) in liver and abdominal organs assessed using Dixon MRI before and after the 6-week intervention.
Time frame: 6 weeks
Change in Intestinal Permeability Measured by T2* MRI.
T2\* values in gut wall tissue will be compared before and after the intervention as a proxy for gut permeability.
Time frame: 6 weeks
Investigation the presence of gene variants such as MUC2, encoding Mucin protein, that are associated with gut permeability.
Genetic variants such as MUC2 will be determined where consent for genetic analysis is given.
Time frame: 6 weeks
Change in Systolic Blood Pressure (mmHg)
Change in Systolic Blood Pressure (mmHg) before and after the 6-week intervention.
Time frame: 6 weeks
Change in Diastolic Blood Pressure (mmHg)
Change in Diastolic Blood Pressure (mmHg) before and after the 6-week intervention.
Time frame: 6 weeks
Change in Heart Rate (beats/minute)
Change in Heart Rate (beats/minute) before and after the 6-week intervention.
Time frame: 6 weeks
Change in Waist-to-Hip Ratio
Change in Waist-to-Hip Ratio before and after the 6-week intervention.
Time frame: 6 weeks
Noor K Al-Tameemi, PhD student candidate
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