High-Protein Diet for Improving Alcoholic Fatty Liver Disease (HP-AFLD-RCT)

June 4, 2026 updated by: Li Lab,MD

Efficacy and Safety of a High-Protein Diet Versus a Standard Diet in Patients With Alcoholic Fatty Liver Disease: A Randomized Controlled Trial

Alcohol-associated liver disease (ALD) is a major cause of mortality from malignant liver diseases, accounting for 47.9% of cirrhosis-related deaths and 30% of liver cancer-related deaths annually. In China, both alcohol consumption and the prevalence of ALD (approximately 5.15%) are on the rise, making ALD an increasingly significant health concern for the population. Alcohol-associated fatty liver disease (AFLD), as the initial and most reversible stage of ALD, is primarily characterized by excessive hepatic lipid deposition, mild liver injury accompanied by mild inflammation. It can progressively develop into alcoholic hepatitis, and in some patients, advance to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Currently, there is a lack of effective clinical treatments for AFLD. Although alcohol abstinence remains the optimal choice for reversing AFLD, it is often difficult for individuals with alcohol dependence to maintain.

A high-protein diet generally refers to a dietary pattern where protein accounts for more than 20% of total energy intake. A protein contribution of 30% is a common ratio in research investigating high-protein dietary interventions for metabolic diseases. Population-based intervention studies have demonstrated that a high-protein diet at this ratio significantly reduces hepatic fat content. For instance, a study published in Gastroenterology (2017) reported that a 6-week isocaloric high-protein diet (macronutrient distribution: 30% protein, 40% carbohydrates, 30% fat) significantly improved hepatic lipid deposition in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Research in Diabetologia (2019) showed that a 6-week isocaloric high-protein diet (30% protein, 30% carbohydrates, 40% fat) significantly reduced hepatic fat content in patients with T2DM. Additionally, a study in Liver International (2020) indicated that a 3-week energy-restricted high-protein diet (30% protein, 35%-45% carbohydrates, 25%-30% fat) significantly decreased hepatic fat content in NAFLD patients. Importantly, none of the aforementioned studies reported adverse events associated with the high-protein dietary interventions. Furthermore, a population-based intervention study published in Annals of Internal Medicine revealed that a low-carbohydrate, high-fat diet was more effective than a high-carbohydrate, low-fat diet in reducing hepatic fat content over a 6-month period in patients with NAFLD and T2DM. These findings suggest that increasing the percentage of energy from protein by reducing carbohydrate intake may yield superior improvements. Based on the macronutrient distributions from the referenced population interventions, and considering that a 30% fat energy contribution closely aligns with the typical dietary fat intake of the Chinese AFLD population, we established the macronutrient distribution for the high-protein diet group as 30% protein, 40% carbohydrates, and 30% fat.

This study intends to conduct a randomized controlled trial to investigate the effects of increasing the percentage of energy from protein under an isocaloric dietary pattern on liver function, hepatic fat content, and glucose-lipid metabolism in individuals with AFLD. The aim is to elucidate the mechanisms underlying its beneficial effects on AFLD, thereby providing population-based evidence and strategies for health promotion in this patient group.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

72

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged between 30 and 65 years old.
  2. Able to understand the study and voluntarily sign the informed consent form.
  3. Meet the clinical diagnostic criteria for alcohol-associated fatty liver disease (AFLD): a history of alcohol consumption for ≥5 years, with an average daily ethanol intake of ≥20 g/d; clinically diagnosed with fatty liver (indicated by abdominal ultrasound or a liver MRI proton density fat fraction [MRI-PDFF] ≥5.2%).

Exclusion Criteria:

  1. Average daily ethanol intake >80 g/d.
  2. Presence of other hepatobiliary diseases, such as autoimmune liver disease, viral hepatitis, liver fibrosis, or cirrhosis.
  3. Presence of severe cardiovascular or cerebrovascular diseases, or renal insufficiency.
  4. Patients with tumors or other severe systemic diseases.
  5. Patients with gastrointestinal disorders, or those with known protein allergy or intolerance.
  6. Long-term use of medications known to cause hepatic steatosis or steatohepatitis (e.g., amiodarone or tamoxifen), nutritional supplements, or probiotics.
  7. Total daily energy intake (excluding energy from alcohol) <1900 kcal or ≥2900 kcal.
  8. Participation in another interventional study within the past year, or scheduled to receive non-study treatments during the trial period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: high protein diet group
Arm Description: High-protein meals will be provided for 5 days per week, and high-protein recipes will be provided for the two weekend days.
Dietary supplement: high protein diet
high protein diet
Placebo Comparator: control diet group
Control meals will be provided for 5 days per week, and control recipes will be provided for the two weekend days.
Dietary supplement: control diet
control diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Magnetic Resonance Imaging proton density fat fraction in hepatic steatosis
Time Frame: Baseline, up to 60 days of the study
Magnetic Resonance Imaging (MRI) technology utilizes magnetic fields and radiofrequency pulses to conduct non-invasive examinations of tissues. When measuring liver fat content, MRI employs water-fat separation techniques to quantify the proton density of water molecules and fat molecules (PDFF) within the liver, thereby providing a quantitative analysis of fat content.
Baseline, up to 60 days of the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liver function
Time Frame: Baseline, up to 60 days of the study
Alanine aminotransferase (ALT, U/L), aspartate aminotransferase (AST, U/L), γ-glutamyltransferase (γ-GT, U/L), alkaline phosphatase (ALP, U/L), total bilirubin (TBIL, μmol/L), direct bilirubin (DBIL, μmol/L), indirect bilirubin (IBIL, μmol/L), alcohol dehydrogenase (ADH, U/L), aldehyde dehydrogenase (ALDH, U/L).
Baseline, up to 60 days of the study
Glucose metabolism
Time Frame: Baseline, up to 60 days of the study
Hemoglobin A1c (HbA1c, %), Fasting blood glucose (FBG, mmol/L)
Baseline, up to 60 days of the study
Lipid metabolism
Time Frame: Baseline, up to 60 days of the study
Serum triglycerides (TG, mmol/L), total cholesterol (TC, mmol/L), low-density lipoprotein cholesterol (LDL-C, mmol/L), high-density lipoprotein cholesterol (HDL-C, mmol/L), apolipoprotein A-I (ApoA-I, g/L), apolipoprotein B (Apo B, g/L).
Baseline, up to 60 days of the study

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inflammation level
Time Frame: Baseline, up to 60 days of the study
High-sensitivity C-reactive protein (hs-CRP, mg/L), tumor necrosis factor (TNF-α, pg/mL), interleukins (IL-1β, pg/mL), interleukins (IL-6, pg/mL).
Baseline, up to 60 days of the study
Kidney function
Time Frame: Baseline, up to 60 days of the study
Blood creatinine (CREA, μmol/L), urea nitrogen (BUN, mmol/L), uric acid (UA, μmol/L).
Baseline, up to 60 days of the study
Intestinal flora
Time Frame: Baseline, up to 60 days of the study
16s rRNA sequencing
Baseline, up to 60 days of the study
serum untargeted metabolomics
Time Frame: Baseline, up to 60 days of the study
serum untargeted metabolomics
Baseline, up to 60 days of the study
biomarkers of oxidative stress
Time Frame: Baseline, up to 60 days of the study
Urinary 8-isoprostane(pg/mL)
Baseline, up to 60 days of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Li Lab,MD

Investigators

  • Study Chair: Songtao Li, Zhejiang Chinese Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

May 29, 2026

First Submitted That Met QC Criteria

June 4, 2026

First Posted (Actual)

June 8, 2026

Study Record Updates

Last Update Posted (Actual)

June 8, 2026

Last Update Submitted That Met QC Criteria

June 4, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-AFLD-RCT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Protect volunteers' personal health data and personal privacy

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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