Effects of Fructose Restriction on Liver Steatosis

Study Overview
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Brief Summary
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Nonalcoholic fatty liver disease (NAFLD) is an emerging health problem as it can lead to end stage liver failure and cardiovascular complications. Diet play an important role in the development of NAFLD. Many studies have addressed the effects of added fructose on NAFLD. To date, little attention has been paid to the effects of a diet devoid of fructose. Therefore, the investigators aim to study the effects of fructose restriction on hepatic fat accumulation and vascular function using a double-blind randomized placebo-controlled design.

Official Title
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Effects of Fructose Restriction on Liver Steatosis

Conditions
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Nonalcoholic Fatty Liver Disease, Glucose Metabolism Disorders, Endothelial Dysfunction

Intervention / Treatment
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* Dietary Supplement: Glucose
* Dietary Supplement: Fructose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Body mass index ≥ 28 kg/m2 Fatty liver index ≥ 60 Fructose intake ≥45 grams/day Exclusion Criteria: Medical history of liver disease (History of) excessive alcohol consumption (defined as > 2 units/day for women, and > 3 units/day for men) Major change in weight and/or physical activity prior to the study Use of glucose lowering drugs Recent illness Pregnancy and/or lactation Contraindications for magnetic resonance imaging Inability to give informed consent Protocol change (implemented on July 18, 2018): in order to increase the inclusion of study participants, subjects with an average daily fructose intake < 45 gram/day will also be eligible for participation. In subjects who have an average daily fructose intake < 45 gram/day, supplementation of either fructose or glucose (see 'Arms and Interventions') will be increased to 45 gram/day.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double blind, randomized controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glucose<br>Participants will follow a six-week low fructose diet. The amount of restricted fructose will be supplemented as glucose powder. | Dietary Supplement: Glucose<br>* Participants will adhere to a fructose restricted diet for a period of six weeks (<7.5 grams/meal and/or <10 grams/day; ad-libitum intake). In addition, the amount of fructose that will be restricted - which is based on the average individual fructose intake assessed prior to randomization - will be supplemented as glucose powder three times daily during the meal.<br>|
| Placebo Comparator: Fructose<br>Participants will follow a six-week low fructose diet. The amount of restricted fructose will be supplemented as fructose powder. | Dietary Supplement: Fructose<br>* Participants will adhere to a fructose restricted diet for a period of six weeks (<7.5 grams/meal and/or <10 grams/day; ad-libitum intake). In addition, the amount of fructose that will be restricted - which is based on the average individual fructose intake assessed prior to randomization - will be supplemented as fructose powder three times daily during the meal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in intrahepatic triglyceride content | Assessed by magnetic resonance spectroscopy | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in arterial stiffness (PWV) | Assessed by pulse wave velocity | 6 weeks | 
| Change in endothelial function (flowmotion and skin heating response) | Assessed by laser doppler flowmetry | 6 weeks | 
| Change in endothelial function (RHI) | Assessed by reactive hyperemia peripheral arterial tonometry | 6 weeks | 
| Change in endothelial function (panel of endothelial dysfunction biomarkers) | Assessed by plasma biomarkers | 6 weeks | 
| Change in glucose metabolism | Assessed by a standard 75-gram oral glucose tolerance test | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fructose, Diet