Liver, Diet and Genetic Background

NCT ID: NCT04644887

Last Updated: 2024-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-12
• Study Completion Date: 2021-12-31

Brief Summary

PNPLA3 rs738409 (I148M) variant is associated with hepatic liver accumulation and chronic liver diseases including non-alcoholic fatty liver disease. It has been shown that obesity augments genetic risk but studies investigating the interaction of PNPLA3 rs738409 risk variant and diet are scarce. The aim is to investigate the effect of dietary fat quality modification in participants with different variants of the PNPLA3 gene (rs738409). The primary outcome is the change in liver fat measured by magnetic resonance imaging in the randomized controlled 12-week dietary intervention trial.

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The composition of the diet, especially quality of dietary fat, contributes to the susceptibility to hepatic lipid accumulation. Saturated fatty acids (SFA), but not polyunsaturated fatty acids (PUFA) increases intrahepatic triglycerides with and without concomitant weight gain. Therefore, the modification of dietary fat quality is the key dietary approach for the prevention of NAFLD.

PNPLA3 rs738409 (I148M) variant is associated with hepatic liver accumulation and chronic liver diseases including NAFLD. It has been shown that obesity augments genetic risk but studies investigating the interaction of PNPLA3 rs738409 risk variant and diet are scarce. Therefore, the aim is to investigate the effect of dietary fat quality modification (high unsaturated fat vs. high SFA) on liver fat and lipid and glucose metabolism in participants with different variants (CC or GG) of the PNPLA3 gene.

The investigators will conduct the randomized controlled 12-week dietary intervention trial in participants with different homozygous PNPLA3 variants (CC or GG). The primary outcome of the intervention is in the amount of liver fat measured by nuclear magnetic resonance imaging (MRI). Altogether 140 homozygous participants (PNPLA3 rs738409 CC and GG) will be recruited from the Metabolic Syndrome in Men (METSIM) study. The inclusion criteria include BMI < 35 kg/m2 and age < 75 years. The main exclusion criteria include diabetes, acute illness, or current evidence of acute or chronic inflammatory or infective diseases.

Dietary guidance in the intervention group is based on the Nordic and Finnish nutrition recommendations with an emphasis on the quality of dietary fat. The aims for the intake of fatty acids will be SFA < 10 % of energy intake (E%) and mono- and polyunsaturated fatty acids (UFA) >2/3 of the total fat intake.

The diet of the control group corresponds to the average nutrient intake in the Nordic countries, i.e. the intake of SFA about 15 E% and the proportion of UFA about 50 % of total fat intake.

Conditions

Liver Fat

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Healthy diet CC genotype

The participants will follow the intervention diet during the 12-week intervention period.

Group Type: EXPERIMENTAL

Dietary intervention: Healthy diet

Intervention Type: OTHER

Dietary guidance in the intervention group is based on the Nordic and Finnish nutrition recommendations with an emphasis on the quality of dietary fat. The aims for the intake of fatty acids will be SFA \< 10 % of energy intake (E%) and mono- and polyunsaturated fatty acids (UFA) \>2/3 of the total fat intake. The key food products such as vegetable oil-based spread, liquid margarine and canola oil are provided to the participants. The participants are recommended to use fat free (e.g. milk, sourdough milk and yogurt) and low fat (e.g. cheese ≤ 17%) dairy products and low-fat meat, poultry, and fish as well as natural nuts and seeds.

Control diet CC genotype

The participants will follow the control diet during the 12-week intervention period.

Group Type: ACTIVE_COMPARATOR

Dietary intervention: Control diet

Intervention Type: OTHER

The control diet corresponds to the average nutrient intake in the Nordic countries, i.e. the intake of SFA about 15 E% and the proportion of UFA about 50 % of total fat intake. The participants of the control group will get butter-based spread for bread and cooking. They are recommended to use semi-skimmed milk (1,5 %), normal fat yogurt (\~2%), normal fat cheese (\~24-35 %) and avoid consumption of vegetable oils. They are allowed to eat a portion of fish and nuts once a week.

Healthy diet GG genotype

The participants will follow the intervention diet during the 12-week intervention period.

Group Type: EXPERIMENTAL

Dietary intervention: Healthy diet

Intervention Type: OTHER

Dietary guidance in the intervention group is based on the Nordic and Finnish nutrition recommendations with an emphasis on the quality of dietary fat. The aims for the intake of fatty acids will be SFA \< 10 % of energy intake (E%) and mono- and polyunsaturated fatty acids (UFA) \>2/3 of the total fat intake. The key food products such as vegetable oil-based spread, liquid margarine and canola oil are provided to the participants. The participants are recommended to use fat free (e.g. milk, sourdough milk and yogurt) and low fat (e.g. cheese ≤ 17%) dairy products and low-fat meat, poultry, and fish as well as natural nuts and seeds.

Control diet GG genotype

The participants will follow the control diet during the 12-week intervention period.

Group Type: ACTIVE_COMPARATOR

Dietary intervention: Control diet

Intervention Type: OTHER

The control diet corresponds to the average nutrient intake in the Nordic countries, i.e. the intake of SFA about 15 E% and the proportion of UFA about 50 % of total fat intake. The participants of the control group will get butter-based spread for bread and cooking. They are recommended to use semi-skimmed milk (1,5 %), normal fat yogurt (\~2%), normal fat cheese (\~24-35 %) and avoid consumption of vegetable oils. They are allowed to eat a portion of fish and nuts once a week.

Interventions

Dietary intervention: Healthy diet

Dietary guidance in the intervention group is based on the Nordic and Finnish nutrition recommendations with an emphasis on the quality of dietary fat. The aims for the intake of fatty acids will be SFA \< 10 % of energy intake (E%) and mono- and polyunsaturated fatty acids (UFA) \>2/3 of the total fat intake. The key food products such as vegetable oil-based spread, liquid margarine and canola oil are provided to the participants. The participants are recommended to use fat free (e.g. milk, sourdough milk and yogurt) and low fat (e.g. cheese ≤ 17%) dairy products and low-fat meat, poultry, and fish as well as natural nuts and seeds.

Intervention Type: OTHER

Dietary intervention: Control diet

The control diet corresponds to the average nutrient intake in the Nordic countries, i.e. the intake of SFA about 15 E% and the proportion of UFA about 50 % of total fat intake. The participants of the control group will get butter-based spread for bread and cooking. They are recommended to use semi-skimmed milk (1,5 %), normal fat yogurt (\~2%), normal fat cheese (\~24-35 %) and avoid consumption of vegetable oils. They are allowed to eat a portion of fish and nuts once a week.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• PNPLA3 rs738409, CC or GG
• Body mass index (BMI) < 35 kg/m2
• Total cholesterol < 8 mmol/l
• LDL cholesterol < 5 mmol/l
• Fasting plasma glucose < 7 mmol/l
• Plasma alanine aminotransferase (ALT) < 100 U/l
• Age 60-75 y

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Kuopio University Hospital

OTHER

Sponsor Role: collaborator

University of Eastern Finland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ursula Schwab, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Eastern Finland

Locations

Institute of Public Health and Clinical Nutriton

Kuopio, , Finland

Countries

Finland

Other Identifiers

LIDIGE

Identifier Type: -

Identifier Source: org_study_id