Effects of Fructose Restriction on Liver Steatosis (FRUITLESS)

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.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism Disorders; Endothelial Dysfunction; Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Glucose; Dietary supplement: Fructose

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6200 MD
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glucose; Participants will follow a six-week low fructose diet. The amount of restricted fructose will be supplemented as glucose powder.	Dietary supplement: Glucose; 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.
Placebo Comparator: Fructose; Participants will follow a six-week low fructose diet. The amount of restricted fructose will be supplemented as fructose powder.	Dietary supplement: Fructose; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Martijn CG Brouwers, MD,PhD, Maastricht University Medical Center

Publications and helpful links

General Publications

• Janssen LEF, Simons N, Simons PIHG, Schaper NC, Feskens EJM, van der Ploeg LMC, Van den Eynde MDG, Schalkwijk CG, Houben AJHM, Stehouwer CDA, Brouwers MCGJ. Effects of fructose restriction on blood pressure: Secondary analysis of a double-blind randomized controlled trial. Clin Nutr ESPEN. 2022 Oct;51:97-103. doi: 10.1016/j.clnesp.2022.07.009. Epub 2022 Jul 30.
• Simons N, Veeraiah P, Simons PIHG, Schaper NC, Kooi ME, Schrauwen-Hinderling VB, Feskens EJM, van der Ploeg EMCL, Van den Eynde MDG, Schalkwijk CG, Stehouwer CDA, Brouwers MCGJ. Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial. Am J Clin Nutr. 2021 Feb 2;113(2):391-400. doi: 10.1093/ajcn/nqaa332.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2017
• Primary Completion (Actual): December 20, 2019
• Study Completion (Actual): December 20, 2019

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): February 21, 2020
• Last Update Submitted That Met QC Criteria: February 20, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Fructose; Diet
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Metabolic Diseases; Glucose Metabolism Disorders
• Other Study ID Numbers: 162034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No