Effect of Plant-based Diets on Liver Biomarkers, Cardiometabolic Health, and Exposure to Environmental Contaminants and Endocrine Disruptors in Patients With Metabolic Liver Disease.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Body weight
Study Overview
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.
Detailed Description
Metabolic dysfunction-associated liver disease (MetLD) is currently the most prevalent chronic liver disease worldwide, representing the hepatic manifestation of metabolic syndrome and closely associated with obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension. Its global burden continues to rise in parallel with increasing rates of cardiometabolic disorders, posing a major public health challenge. The natural history of MetLD ranges from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Disease progression is influenced by a complex interplay of metabolic, genetic, environmental, and lifestyle-related factors.
Lifestyle modification remains the cornerstone of MetLD management, with dietary intervention being a key therapeutic strategy. Current clinical guidelines recommend the Mediterranean diet as the standard dietary approach, given its demonstrated benefits in reducing hepatic steatosis, improving insulin sensitivity, lowering systemic inflammation, and enhancing overall cardiometabolic health. Notably, these benefits have been observed even in the absence of substantial weight loss.
In recent years, plant-based dietary patterns have gained increasing attention due to their potential to further improve metabolic and hepatic outcomes. Diets rich in plant-derived foods are characterized by higher intakes of dietary fiber, polyphenols, antioxidants, and unsaturated fatty acids, alongside lower intakes of saturated fats and cholesterol. These nutritional characteristics may contribute to improved insulin sensitivity, modulation of lipid metabolism, and attenuation of chronic low-grade inflammation.
Furthermore, plant-based diets may influence liver health through mechanisms beyond traditional metabolic pathways. Emerging evidence highlights the role of environmental contaminants and endocrine-disrupting chemicals in the pathogenesis and progression of MetLD. Compounds such as per- and polyfluoroalkyl substances (PFAS) and heavy metals (e.g., cadmium, lead, mercury) have been associated with oxidative stress, mitochondrial dysfunction, alterations in glucose and lipid homeostasis, and hepatic injury. These contaminants are known to bioaccumulate predominantly in animal-derived foods, including fish, seafood, red meat, and organ meats. Therefore, dietary patterns that reduce or eliminate animal-based foods may lower internal exposure to these harmful substances.
In addition to environmental exposures, genetic susceptibility and gut microbiota composition play critical roles in MetLD development and progression. Genetic variants such as PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13 have been consistently associated with liver fat accumulation, inflammation, and fibrosis. Meanwhile, the gut microbiota acts as a key regulator of host metabolism and immune function through the gut-liver axis, influencing bile acid metabolism, short-chain fatty acid production, and inflammatory signaling pathways. Diet is one of the main determinants of microbiota composition and function, and plant-based diets have been associated with increased microbial diversity and beneficial metabolic profiles.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Care Provider, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Traditional Mediterranean diet
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.
Intervention: Traditional Mediterranean diet (Other)
Vegan Mediterranean diet
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.
Intervention: Vegan Mediterranean diet (Other)
Outcomes
Primary Outcomes
Body weight
Time Frame: Baseline and 12 weeks
Change from baseline to 12 weeks in body weight (kg), measured using bioelectrical impedance analysis under standardized conditions.
Hepatic steatosis
Time Frame: Baseline and 12 weeks
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)
Secondary Outcomes
- 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)
- Fasting glucose(Baseline and 12 weeks)
- Fasting insulin(Baseline and 12 weeks)
- Total cholesterol(Baseline and 12 weeks)
- Low-density lipoprotein cholesterol(Baseline and 12 weeks)
- High-density lipoprotein cholesterol(Baseline and 12 weeks)
- Triglycerides(Baseline and 12 weeks)
- Iron status(Baseline and 12 weeks)
- Ferritin(Baseline and 12 weeks)
- Transferrin saturation(Baseline and 12 weeks)
- C-reactive protein(Baseline and 12 weeks)
- Neutrophil-to-lymphocyte ratio(Baseline and 12 weeks)
- Gut microbiota alpha diversity(Baseline and 12 weeks)
- Gut microbiota taxonomic composition(Baseline and 12 weeks)
- Serum PFAS concentrations(Baseline and 12 weeks)
- Change in hair heavy metal concentrations (lead, cadmium, mercury, arsenic)(Baseline and 12 weeks)
- Genetic variants(Baseline)
- Health-related quality of life(Baseline and 12 weeks)
- Liver disease-specific quality of life(Baseline and 12 weeks)
Investigators
Miguel López Moreno
Principal Investigator
Universidad Francisco de Vitoria