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| Name | Class |
|---|---|
| Harbin Medical University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| high protein diet group | Experimental | 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. |
|
| control diet group | Placebo Comparator | Control meals will be provided for 6 days per week, and control recipes will be provided for the remainder of the week. |
|
| perilla peptide dietary group | Experimental | The perilla peptide alternative maintains the same total protein intake by partially replacing conventional protein sources with hydrolyzed vegetable protein. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| high protein diet | Dietary Supplement | high protein diet |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Magnetic Resonance Imaging proton density fat fraction in hepatic steatosis | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Liver function | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Inflammation level | 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Qingling Huang, Dr. | Contact | +8615267148306 | hqingling0306@163.com | |
| Kaixin Pan | Contact | +8613568620076 | 18966486859@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Songtao Li | Zhejiang Chinese Medical University | Study Chair |
| Rennan Ren | Harbin Medical University | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31652512 | Background | Marin-Alejandre BA, Abete I, Cantero I, Monreal JI, Elorz M, Herrero JI, Benito-Boillos A, Quiroga J, Martinez-Echeverria A, Uriz-Otano JI, Huarte-Muniesa MP, Tur JA, Martinez JA, Zulet MA. The Metabolic and Hepatic Impact of Two Personalized Dietary Strategies in Subjects with Obesity and Nonalcoholic Fatty Liver Disease: The Fatty Liver in Obesity (FLiO) Randomized Controlled Trial. Nutrients. 2019 Oct 22;11(10):2543. doi: 10.3390/nu11102543. | |
| 20216558 |
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Protect volunteers' personal health data and personal privacy
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| ID | Term |
|---|---|
| D000073600 | Diet, High-Protein |
| ID | Term |
|---|---|
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 |
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Intervention Group: high protein diet Intervention Group: perilla peptide dietary group Control Group: control diet
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| control diet |
| Dietary Supplement |
control diet |
|
| perilla peptide dietary group | Dietary Supplement | perilla peptide dietary group |
|
| Glucose metabolism | Hemoglobin A1c (HbA1c, %), Fasting blood glucose (FBG, mmol/L) | Baseline, up to 60 days of the study |
| Lipid metabolism | 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 |
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 | 16s rRNA sequencing | Baseline, up to 60 days of the study |
| serum untargeted metabolomics | serum untargeted metabolomics | Baseline, up to 60 days of the study |
| biomarkers of oxidative stress | Urinary 8-isoprostane(pg/mL) | Baseline, up to 60 days of the study |
| Background |
| Papakonstantinou E, Triantafillidou D, Panagiotakos DB, Koutsovasilis A, Saliaris M, Manolis A, Melidonis A, Zampelas A. A high-protein low-fat diet is more effective in improving blood pressure and triglycerides in calorie-restricted obese individuals with newly diagnosed type 2 diabetes. Eur J Clin Nutr. 2010 Jun;64(6):595-602. doi: 10.1038/ejcn.2010.29. Epub 2010 Mar 10. |
| 35571881 | Background | Sun P, Huang L, Shuai P, Wan Z, Liu Y, Xue J, Liu Y. Effect of a High Protein, Low Glycemic Index Dietary Intervention on Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial. Front Nutr. 2022 Apr 27;9:863834. doi: 10.3389/fnut.2022.863834. eCollection 2022. |
| 32652799 | Background | Xu C, Markova M, Seebeck N, Loft A, Hornemann S, Gantert T, Kabisch S, Herz K, Loske J, Ost M, Coleman V, Klauschen F, Rosenthal A, Lange V, Machann J, Klaus S, Grune T, Herzig S, Pivovarova-Ramich O, Pfeiffer AFH. High-protein diet more effectively reduces hepatic fat than low-protein diet despite lower autophagy and FGF21 levels. Liver Int. 2020 Dec;40(12):2982-2997. doi: 10.1111/liv.14596. Epub 2020 Jul 21. |
| 31338545 | Background | Skytte MJ, Samkani A, Petersen AD, Thomsen MN, Astrup A, Chabanova E, Frystyk J, Holst JJ, Thomsen HS, Madsbad S, Larsen TM, Haugaard SB, Krarup T. A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial. Diabetologia. 2019 Nov;62(11):2066-2078. doi: 10.1007/s00125-019-4956-4. Epub 2019 Jul 23. |
| 27765690 | Background | Markova M, Pivovarova O, Hornemann S, Sucher S, Frahnow T, Wegner K, Machann J, Petzke KJ, Hierholzer J, Lichtinghagen R, Herder C, Carstensen-Kirberg M, Roden M, Rudovich N, Klaus S, Thomann R, Schneeweiss R, Rohn S, Pfeiffer AF. Isocaloric Diets High in Animal or Plant Protein Reduce Liver Fat and Inflammation in Individuals With Type 2 Diabetes. Gastroenterology. 2017 Feb;152(3):571-585.e8. doi: 10.1053/j.gastro.2016.10.007. Epub 2016 Oct 17. |
| 38299591 | Background | Mackowiak B, Fu Y, Maccioni L, Gao B. Alcohol-associated liver disease. J Clin Invest. 2024 Feb 1;134(3):e176345. doi: 10.1172/JCI176345. |
| Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |