Endothelial Dysfunction, Glucose Metabolism Disorders, Nonalcoholic Fatty Liver Disease
Conditions
Keywords
Fructose, Diet
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTGlucose
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.
DIETARY_SUPPLEMENTFructose
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.
Sponsors
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
double blind, randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in intrahepatic triglyceride content | 6 weeks | Assessed by magnetic resonance spectroscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in arterial stiffness (PWV) | 6 weeks | Assessed by pulse wave velocity |
| Change in endothelial function (flowmotion and skin heating response) | 6 weeks | Assessed by laser doppler flowmetry |
| Change in endothelial function (RHI) | 6 weeks | Assessed by reactive hyperemia peripheral arterial tonometry |
| Change in endothelial function (panel of endothelial dysfunction biomarkers) | 6 weeks | Assessed by plasma biomarkers |
| Change in glucose metabolism | 6 weeks | Assessed by a standard 75-gram oral glucose tolerance test |
Countries
Netherlands
Outcome results
None listed