Effect of Plant-based Diets on Liver Biomarkers, Cardiometabolic Health, and Exposure to Environmental Contaminants and Endocrine Disruptors in Patients With Metabolic Liver Disease.

NCT07503431 | Not Yet Recruiting

• 1 other identifier: PI 22/26
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Plant-based diets have gained increasing recognition for their sustainability and their benefits on cardiometabolic and liver health. However, evidence regarding their effects in patients with metabolic liver disease (MetLD) remains limited. The primary objective of this project is to compare the effects of a traditional Mediterranean diet and a Mediterranean diet exclusively based on plant-derived foods on liver parameters, cardiometabolic health, gut microbiota, and exposure to environmental contaminants in patients with MetLD. This study is a randomized clinical trial with a 1:1 allocation ratio into two groups: a traditional Mediterranean diet, considered the standard diet in our setting and recommended for this condition, and a Mediterranean diet exclusively based on plant-derived foods, both designed by registered dietitians. The intervention will last 12 weeks. Anthropometric, metabolic, hepatic, inflammatory, and quality of life variables will be assessed. Additionally, gut microbiota, genetic variants associated with MetLD, and internal exposure to environmental contaminants will be evaluated using biological samples. A 4-week follow-up after the intervention will also be conducted to assess the integration of lifestyle recommendations among participants. The results will contribute to the development of safe, sustainable, and cost-effective nutritional strategies and may serve as a basis for future clinical guidelines integrating precision nutrition and planetary health in the management of chronic liver diseases. The traditional Mediterranean diet has shown metabolic and hepatic benefits; however, its reformulation toward a predominantly plant-based pattern may enhance these effects by reducing saturated fat intake and increasing the consumption of fiber, bioactive compounds, and fatty acids with a more favorable profile. Moreover, this type of diet limits the intake of animal-based foods associated with the bioaccumulation of environmental contaminants such as PFAS and heavy metals, which are increasingly implicated in the progression of MetLD. This project hypothesizes that a Mediterranean diet based exclusively on plant-derived foods, compared to a traditional Mediterranean diet, will lead to greater improvements in hepatic, metabolic, and inflammatory parameters in patients with MetLD, and will additionally be associated with a lower internal burden of bioaccumulative environmental contaminants. Primary objective To evaluate the effect of a Mediterranean diet based exclusively on plant-derived foods on MetLD, assessed non-invasively through biochemical and elastographic parameters. Secondary objectives To evaluate changes in metabolic parameters, anthropometric measures, and body composition. To examine changes in systemic inflammatory markers, such as C-reactive protein and the neutrophil-to-lymphocyte ratio. To assess exposure to environmental contaminants, specifically heavy metals (lead, cadmium, mercury) and endocrine disruptors such as perfluorinated compounds (PFAS), and their relationship with liver damage. To evaluate whether genetic variants associated with susceptibility to and progression of MetLD modulate hepatic and metabolic responses to dietary patterns. To analyze changes in gut microbiota following the plant-based diet and their association with liver improvement.

Conditions

Metabolic Dysfunction-associated Liver Disease

Keywords

Metabolic dysfunction-associated liver disease; plant-based diet; mediterranean diet

Outcome Measures

Primary Outcomes (2)

• Body weight

  Change from baseline to 12 weeks in body weight (kg), measured using bioelectrical impedance analysis under standardized conditions.

  Baseline and 12 weeks

• Hepatic steatosis

  Change from baseline to 12 weeks in hepatic steatosis measured non-invasively using transient elastography. Hepatic steatosis will be assessed by the controlled attenuation parameter (CAP, dB/m)

  Baseline and 12 weeks

Secondary Outcomes (23)

• Liver stiffness

  Baseline and 12 weeks

• Fat mass

  Baseline and 12 weeks

• Waist circumference

  Baseline and 12 weeks

• Systolic blood pressure

  Baseline and 12 weeks

• Diastolic blood pressure

  Baseline and 12 weeks

Study Arms (2)

Traditional Mediterranean diet

EXPERIMENTAL

This dietary pattern is considered the standard of care in the study setting and includes a balanced intake of plant- and animal-derived foods, consistent with current clinical recommendations for metabolic liver disease. The diet emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat. Moderate intake of fish, poultry, eggs, and low-fat dairy products will be encouraged, while red and processed meats, added sugars, and ultra-processed foods will be limited.

Other: Traditional Mediterranean diet

Vegan Mediterranean diet

EXPERIMENTAL

This dietary pattern is designed and supervised by registered dietitians and emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat, in line with Mediterranean dietary principles. All animal-derived foods (including meat, fish, seafood, dairy products, and eggs) will be excluded. Legumes, whole grains, nuts, and seeds will serve as the main sources of protein and healthy fats. Participants will be encouraged to prioritize whole, minimally processed foods; however, plant-based alternatives to meat and dairy may be allowed in cases where necessary to support adherence.

Other: Vegan Mediterranean diet

Interventions

Traditional Mediterranean diet OTHER

This dietary pattern is considered the standard of care in the study setting and includes a balanced intake of plant- and animal-derived foods, consistent with current clinical recommendations for metabolic liver disease. The diet emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat. Moderate intake of fish, poultry, eggs, and low-fat dairy products will be encouraged, while red and processed meats, added sugars, and ultra-processed foods will be limited.

Traditional Mediterranean diet

Vegan Mediterranean diet OTHER

This dietary pattern is designed and supervised by registered dietitians and emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat, in line with Mediterranean dietary principles. All animal-derived foods (including meat, fish, seafood, dairy products, and eggs) will be excluded. Legumes, whole grains, nuts, and seeds will serve as the main sources of protein and healthy fats. Participants will be encouraged to prioritize whole, minimally processed foods; however, plant-based alternatives to meat and dairy may be allowed in cases where necessary to support adherence.

Vegan Mediterranean diet

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 to 75 years.
• Diagnosis of metabolic dysfunction-associated liver disease (MetLD) based on evidence of hepatic steatosis by ultrasound or transient elastography with controlled attenuation parameter (CAP) ≥ 275 dB/m, or liver biopsy.
• Body mass index (BMI) between 25 and 38.5 kg/m².

You may not qualify if:

• Liver disease of etiology other than MetLD.
• Any condition requiring specific dietary treatment and/or limiting adherence to a plant-based diet.
• Acute or chronic diseases that may reduce life expectancy.
• Type 1 diabetes mellitus.
• Use of weight-loss medications (e.g., incretin-based therapies) or initiation of glucose-lowering medication within the past 6 months.
• Pregnancy or breastfeeding.
• Pharmacological treatments that may interfere with study outcomes (e.g., corticosteroids or biological therapies).
• Uncontrolled psychiatric disorders.
• Inability to provide informed consent.

Sponsors & Collaborators

• Universidad Francisco de Vitoria: lead
• IMDEA Food: collaborator
• Hospital Clinico Universitario San Cecilio: collaborator
• Hospital Universitario Puerta del Hierro: collaborator

Study Sites (1)

Hospital Puerta del Hierro

Madrid, Spain

Location

Related Publications (6)

• Younossi ZM, Zelber-Sagi S, Lazarus JV, Wong VW, Yilmaz Y, Duseja A, Eguchi Y, Castera L, Pessoa MG, Oliveira CP, El-Kassas M, Tsochatzis E, Fan JG, Spearman CW, Tacke F, Castellanos Fernandez MI, Alkhouri N, Schattenberg JM, Romero-Gomez M, Noureddin M, Allen AM, Ong JP, Roberts SK, Shubrook JH, Burra P, Kohli R, Kautz A, Holleboom AG, Lam B, Isaacs S, Macedo P, Gastaldelli A, Henry L, Ivancovsky-Wajcman D, Nader F, de Avila L, Price JK, Mark HE, Villota-Rivas M, Barbera A, Kalligeros M, Gerber LH, Alqahtani SA. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis. Gastroenterology. 2025 Oct;169(5):1017-1032.e2. doi: 10.1053/j.gastro.2025.02.044. Epub 2025 Apr 11.

  PMID: 40222485 BACKGROUND

• European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024 Sep;81(3):492-542. doi: 10.1016/j.jhep.2024.04.031. Epub 2024 Jun 7.

  PMID: 38851997 BACKGROUND

• Lopez-Moreno M, Kraselnik A. The Impact of Plant-Based Proteins on Muscle Mass and Strength Performance: A Comprehensive Review. Curr Nutr Rep. 2025 Feb 21;14(1):37. doi: 10.1007/s13668-025-00628-1.

  PMID: 39982647 BACKGROUND

• Lopez-Moreno M, Fresan U. Do the Health Benefits of the Mediterranean Diet Increase with a Higher Proportion of Whole Plant-Based Foods? Curr Nutr Rep. 2025 Mar 26;14(1):52. doi: 10.1007/s13668-025-00647-y.

  PMID: 40138066 BACKGROUND

• López-Moreno M,Marrero-Fernández P,Galiana C,Aguilar-Navarro M,Muñoz A,Gutiérrez-Hellín J,Fresán U

  BACKGROUND

• Lopez-Moreno M, Fresan U, Del Coso J, Aguilar-Navarro M, Iglesias Lopez MT, Pena-Fernandez J, Munoz A, Gutierrez-Hellin J. The OMNIVEG STUDY: Health outcomes of shifting from a traditional to a vegan Mediterranean diet in healthy men. A controlled crossover trial. Nutr Metab Cardiovasc Dis. 2024 Dec;34(12):2680-2689. doi: 10.1016/j.numecd.2024.08.008. Epub 2024 Aug 23.

  PMID: 39358106 BACKGROUND

Central Study Contacts

Miguel López Moreno, PhD

CONTACT

+34 64892334; miguel.lopez@ufv.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: March 25, 2026
• First Posted: March 31, 2026
• Study Start: April 18, 2026
• Primary Completion (Estimated): December 19, 2026
• Study Completion (Estimated): March 10, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)