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

Li Lab,MD

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Alcohol-associated Fatty Liver Disease

Treatments: Dietary Supplement: perilla peptide dietary group; Dietary Supplement: control diet; Dietary Supplement: high protein diet

Study type: Interventional

Funder types: Other

Identifiers

NCT07632222

HP-AFLD-RCT

Details and patient eligibility

About

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.

Enrollment: 74 estimated patients

Sex: All

Ages: 30 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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74 participants in 3 patient groups, including a placebo group

high protein diet group

Experimental group

Description:

Arm Description: High-protein meals will be provided for 6 days per week, and high-protein recipes will be provided for the remainder of the week.

Treatment:

Dietary Supplement: high protein diet

control diet group

Placebo Comparator group

Description:

Control meals will be provided for 6 days per week, and control recipes will be provided for the remainder of the week.

Treatment:

Dietary Supplement: control diet

perilla peptide dietary group

Experimental group

Description:

The perilla peptide alternative maintains the same total protein intake by partially replacing conventional protein sources with hydrolyzed vegetable protein.

Treatment:

Dietary Supplement: perilla peptide dietary group