Effect of Fructose Reduction on Non-alcoholic Fatty Liver Disease (NAFLD) and Metabolic Syndrome in Overweight Children

Investigation on the Preventive Effect of Reduced Fructose Consumption on the Development of Non-alcoholic Fatty Liver Disease in Children in a Long Term Study

The aim of the present study is to find out if a dietary intervention mainly focusing on fructose reduction has a preventive effect on the development and progression of NAFLD and the metabolic syndrome in overweight children.

Study Overview

• Status: Unknown
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Behavioral: dietary intervention mainly focusing on fructose reduction

Detailed Description

In the intervention study a total of 100 overweight and 50 normal weight children, aged 5-8 years have to be included. At the beginning, two 24-h dietary recalls are performed to assess nutritional intake and fructose consumption. Anthropometric parameters (body weight and height) are measured to calculate BMI and BMI-SDS of the children. Physical activity during leisure time as well as socio-demographic status and "family background" are assessed using different questionnaires. An ultrasound examination of the liver is performed in all participants for detection of signs of fatty liver. From each child included in the study a fasting blood sample is taken to determine the following blood parameters: ALT, AST, γ-GT, uric acid, blood lipids (TG, HDL, LDL, Total cholesterol), blood alcohol, PAI-1 and endotoxin concentration. A part of the blood sample is used for DNA-analysis. In all children systolic (SBP) and diastolic (DBP) blood pressure are also measured. An oral glucose tolerance test (OGTT) is performed after an overnight fast of 12 h (glucose concentration: 1.75 g/kg body weight, maximum 75g). Simultaneously a glucose hydrogen breath test is performed to assess small intestinal bacterial overgrowth (SIBO). After the check-ups at the beginning of the study, children are divided into two study groups: the intervention group and the control group. Based on the daily fructose intake assessed at the beginning of the study, children participating in the intervention group are advised to reduce their daily fructose intake by 50%. In the first study year, every three months and in the second study year, every six months, nutritional counseling is repeated in small groups in which parents and children are separately trained. If families participating in the control group wish, they receive a dietary counseling based on the references of the "DGE" at the beginning of the study. After the first and the second study year the examinations are repeated in all participants (ultrasound examination only after the second study year).

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Stuttgart, Baden-Württemberg, Germany, 70599
      • Recruiting
      • University of Hohenheim, Dept. of Nutritional Medicine (180 a)
      • Contact: Ina Bergheim, Ph.D.; Phone Number: ++49/711/4592-4102; Email: ina.bergheim@uni-hohenheim.de
      • Principal Investigator: Ina Bergheim, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 8 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI > 90 percentile for overweight children
• BMI < 90 percentile for normal weight children
• no signs of fatty liver (maximal fatty liver grade one or slightly elevated ALT, AST, γ-GT concentrations)
• children with metabolic disorders (prehypertension, high triglyceride, cholesterol or fasting glucose levels) are included with agreement of the pediatrics

Exclusion Criteria:

• liver disease (e.g. steatohepatitis)
• diabetes type 1 and 2
• renal insufficiency
• chronic disease of the gastrointestinal tract
• taking drugs affecting lipid or glucose metabolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intervention group; Based on the daily fructose intake assessed at the beginning of the study, children participating in the intervention group are advised to reduce their daily fructose intake about 50%.	Behavioral: dietary intervention mainly focusing on fructose reduction; Based on the daily fructose intake assessed at the beginning of the study, children participating in the intervention group are advised to reduce their daily fructose intake by 50%. In the first study year, every three months and in the second study year, every six months, nutritional counseling is repeated in small groups in which parents and children are separately trained.
No Intervention: Control group; Families participating in the control group are given only one dietary counseling based on the references of the "DGE" at the beginning of the study if they wish.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prevalence of fatty liver disease	Prevalence of fatty liver disease in ultrasound examination after 2 years	2 years
changes in blood lipid concentrations	changes in TG, HDL, LDL, total choelsterol concentrations in serum	1, 2 years
changes in blood pressure	changes in systolic (SBP) and diastolic (DBP) blood pressure	1, 2 years
changes in glucose metabolism	changes in oral glucose tolerance-test	1, 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in small intestinal bacterial overgrowth	changes in glucose hydrogen breath test	1, 2 years

Collaborators and Investigators

• Sponsor: University of Hohenheim
• Investigators: Principal Investigator: Ina Bergheim, Ph.D., University of Hohenheim, Dept. of Nutritional Medicine (180 a)

Publications and helpful links

General Publications

• Engstler AJ, Aumiller T, Degen C, Durr M, Weiss E, Maier IB, Schattenberg JM, Jin CJ, Sellmann C, Bergheim I. Insulin resistance alters hepatic ethanol metabolism: studies in mice and children with non-alcoholic fatty liver disease. Gut. 2016 Sep;65(9):1564-71. doi: 10.1136/gutjnl-2014-308379. Epub 2015 May 25.
• Maier IB, Ozel Y, Wagnerberger S, Bischoff SC, Bergheim I. Dietary pattern and leisure time activity of overweight and normal weight children in Germany: sex-specific differences. Nutr J. 2013 Jan 15;12:14. doi: 10.1186/1475-2891-12-14.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Anticipated): December 1, 2011
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: February 25, 2011
• First Submitted That Met QC Criteria: February 28, 2011
• First Posted (Estimate): March 1, 2011

Study Record Updates

• Last Update Posted (Estimate): March 1, 2011
• Last Update Submitted That Met QC Criteria: February 28, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: children; NAFLD; metabolic syndrome; fructose
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Liver Diseases; Fatty Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 03105084 (IB)