Effect of High Protein Diet on Hepatic Steatosis in Patients With MAFLD

Effect of High Protein Diet on Hepatic Steatosis, Inflammation and Mitochondrial Bioenergetics in Patients With MAFLD : A Randomized Controlled Trial

MAFLD is a growing problem in India. Its pathophysiology is complex, but focused on abnormal substrate handling due to mitochondrial dysfunction reflecting as metabolic inflexibility. Nutrition is the cornerstone of management. The ideal macronutrient distribution within a hypocaloric diet is not known yet. Evidence from experimental and a few human studies in obese, highlight the role of dietary proteins, independent of calorie restriction, in reducing hepatic steatosis by improving the cellular and systemic bioenergetics.

Study Overview

• Status: Not yet recruiting
• Conditions: Metabolic Dysfunction Associated Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Normal Protein diet; Dietary supplement: High protein diet

Detailed Description

Novelty: First study to assess the effect of high protein diet (HPD) in comparison to a standard protein diet (SPD) within a calorie restricted diet, on both the cellular and systemic bioenergetics in patients with MAFLD.

Objectives: Aims to see the effect of HPD on hepatic steatosis, cellular and systemic bioenergetics, along with metabolic parameters in patients with MAFLD.

Method: In this RCT, patients with MAFLD (n=140) with or without MS, would be randomized into HPD or SPD groups (i.e. 70 in each group), and parameters like hepatic steatosis (CAP by Transient elastography (FibroScan), cellular bioenergetics by oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) as measured using Seahorse Analyzer, and Indirect Calorimetry will be used to assess the fasting and postglucose challenge (Oral glucose tolerance test) REE and RQ. DEXA scan would be used to assess body composition apart from routine blood tests to assess features of Metabolic syndrome. The serum levels of GLP1, CKK, Ghrelin, FGF21, Adipokines like leptin and adiponectin, NADH/NAD ratio, insulin and glucagon would be measured.

Outcome: A HPD is expected to improve hepatic steatosis, blunted fuel switching (RQ) and cellular bioenergetics (OCR) along with metabolic parameters in patients with MAFLD.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kanika Jain, MSc; Phone Number: 08076030183; Email: kanikjain@gmail.com

Study Locations

• India
  • New Delhi
    • Delhi, New Delhi, India, 110070
      • Institute of Liver and Biliary Sciences
      • Contact: Jaya Benjamin, Dr; Phone Number: 9540951081; Email: jayabenjaminilbs@gmail.com
      • Contact: Kanika Jain, MSc; Phone Number: 8076030183; Email: kanikjain@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed treatment naïve consenting adults with MAFLD (controlled attenuation parameter; CAP >250, BMI>23 and/or DM) Age 18-65 years

Exclusion Criteria:

• • Lean (BMI <23) patients

  • Age <18 and >65 years
  • Individuals who had been hospitalized with complications of Diabetes mellitus, Chronic Kidney disease, Hypertension in the previous 6 months
  • Patients with viral hepatitis
  • Patients with significant alcohol consumption (regular consumption of > 10g per day for females and > 20g/d in males),
  • Patients having chronic inflammatory bowel disease or any chronic and autoimmune diseases will be excluded
  • Pregnant & lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Treatment Group; The intervention is planned as a supervised dietary supplementation, with a goal of restricting the calorie intake to 20 Kcal/Kg BW/day, with a protein intake of 0.9 gm/Kg BW/day i.e., around 15 % of total calories from protein, 25% from fats and 60% from carbohydrates. Physical activity recommendations: Brisk walking on a treadmill (at a speed 5-6 Kmph for 60 minutes) OR 5000 steps per day by pedometer counting.	Dietary supplement: Normal Protein diet; Normal protein diet
Experimental: High Protein Diet; The intervention is planned as a supervised dietary supplementation, with a goal of restricting the calorie intake to 20 Kcal/Kg BW/day, with a protein intake of 1.3 gm/Kg BW/day i.e., around 25 % of total calories from protein, 25% from fats and 50% from carbohydrates. Major portion of the protein would be met by dairy, legumes and pulses along with egg whites. Physical activity recommendations: Brisk walking on a treadmill (at a speed 5-6 Kmph for 60 minutes) OR 5000 steps per day by pedometer counting.	Dietary supplement: High protein diet; High protein diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Hepatic steatosis.	Changes in hepatic steatosis at baseline and follow up would be done using fibro scan (CAP) and Computed Tomography (Liver Attenuation Index).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of cellular bioenergetics would be done.	Changes in oxygen consumption rate (OCR in pmol/min) at baseline and follow up would be done using Seahorse XF analyser.	3 months
Assessment of cellular bioenergetics would be done.	Changes in Extracellular acidification rate(ECAR in mph/min) at baseline and follow up would be done using Seahorse XF analyser.	3 months
Assessment of systemic bioenergetics would be done.	A switch in Respiratory quotient (RQ) at fasting and OGTT would be assessed using indirect calorimetry at baseline and follow up.	3 months
Assessment of metabolic markers at baseline and follow up.	Changes in metabolic markers would be done at baseline and follow up. The following metabolic markers would be assessed :- Blood pressure(systolic and dystolic), HbA1c,Thyroid stimulating hormone , Total lipid profile, CRP levels.	3 months
Assessment of muscle mass.	Assessment of muscle mass would be done by DEXA scan at baseline and follow up.	3 months
Assessment of serum levels of FGF21(in ng/ml) and leptin(in ng/ml).	Assessments would be done using commercially available Elisa kits at baseline and follow up.	3 months
Assessment of serum levels of adiponectin(in μg/mL).	Assessments would be done using commercially available Elisa kits at baseline and follow up.	3 months
Assessment of serum levels of insulin(in μU/mL)	Assessments would be done using commercially available Elisa kits at baseline and follow up.	3 months
Assessment of serum levels of glucagon(in pg/mL).	Assessments would be done using commercially available Elisa kits at baseline and follow up.	3 months
Assessment of serum levels of glucagon like peptide(GLP-1) (in pmol/L)	Assessments would be done using commercially available Elisa kits at baseline and follow up.	3 months
Assessment of serum levels of ghrelin (in fmol/ml).	Assessments would be done using commercially available Elisa kits at baseline and follow up.	3 months
Assessment of serum levels of cholecystokinin (in pmol/liter).	Assessments would be done using commercially available Elisa kits at baseline and follow up.	3 months

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Study Director: Jaya Benjamin, PhD, Institute of Liver and Biliary Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): December 27, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: December 24, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: mitochondrial dysfunction; metabolic inflexibility; FGF21 resistance
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver
• Other Study ID Numbers: ILBS-MAFLD-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No