High Fructose Diet, the Gut Microbiome, and Metabolic Health

NCT06329544 | Recruiting DMC

• 2 other identifiers: STUDY-23-015721R01DK137968-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Americans commonly consume excess amounts of dietary fructose. Added fructose has been shown to have an adverse impact on metabolic health, including increased insulin resistance and type 2 diabetes (T2D) risk. However, the mechanisms that link dietary fructose and metabolic health are poorly understood. Malabsorption or incomplete metabolism of fructose in the small intestine is common in the population. Excess fructose reaches the colon where it may change the structure and function of the gut microbiome, alter bacterial metabolites and trigger inflammatory responses impacting T2D risk. To elucidate whether commonly consumed levels of dietary fructose influence metabolic outcomes through altering the gut microbiome, the research team will randomize 30 participants to a controlled cross-over dietary intervention, in which the participants will consume 12-day isocaloric, added fructose or glucose diets (25% of total calories) separated by a 10-day controlled diet washout period. The research team aims to:

1. 1.Determine the relationships between high fructose consumption, the gut microbiome and metabolic risk.
2. 2.Characterize the causal role(s) that fructose-induced alterations to the gut microbiome have on metabolic risk using a germ-free mouse model.

Conditions

Type 2 Diabetes; Obesity; MASLD

Keywords

Microbiome; MASLD; Obesity; Fructose; Fatty Liver

Outcome Measures

Primary Outcomes (2)

• Liver proton density fat fraction (PDFF)

  Liver proton density fat fraction (PDFF) in %

  year 3

• Degree of fibrosis

  Tissue shear stiffness will be measured in the right hepatic lobe \[in kilopascals (kPa)\] to assess the degree of fibrosis.

  year 3

Study Arms (2)

Fructose Dietary then Glucose Dietary

EXPERIMENTAL

Participants that will be randomized to the 12-day isocaloric weight-maintaining high fructose diet, then will change to the 12-day isocaloric weight-maintaining high glucose diet after a 10-day washout period.

Dietary Supplement: Fructose; Dietary Supplement: glucose

Glucose Dietary then Fructose Dietary

EXPERIMENTAL

Participants that will be randomized to the 12-day isocaloric weight-maintaining high glucose diet, then will change to the12-day isocaloric weight-maintaining high fructose diet after a 10-day washout period.

Dietary Supplement: Fructose; Dietary Supplement: glucose

Interventions

Fructose DIETARY_SUPPLEMENT

12-day isocaloric weight-maintaining high fructose diet (25% total calories from added fructose)

Fructose Dietary then Glucose Dietary; Glucose Dietary then Fructose Dietary

glucose DIETARY_SUPPLEMENT

12-day isocaloric weight-maintaining high glucose diet (25% total calories from added glucose)

Fructose Dietary then Glucose Dietary; Glucose Dietary then Fructose Dietary

Eligibility Criteria

• Age: 25 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must be determined to be a fructose malabsorber (screening visit) via hydrogen breath test.

You may not qualify if:

• Use of probiotic/prebiotic/synbiotic supplements
• Consumption of \> 1 sugar sweetened beverage per day
• Antibiotics within 3 months prior to enrollment or during intervention
• Vegetarian, vegan or other restrictive dietary habits
• Food allergy
• Alcohol consumption in excess of 2 drink per day
• Physician diagnosis of a major medical illness (including type 1 or type 2 diabetes) or eating disorder
• Physical, mental, or cognitive handicaps that prevent participation
• Chronic use of any medication that may affect body weight or composition, insulin resistance, or lipid profiles;
• Current smoking (more than 1 cigarette in the past week) or use of other recreational drugs; e) restrictive dietary habits;
• food allergy;
• excess alcohol consumption;
• recent use of pro-, pre- or Synbiotics of receipt of antibiotics within 3 months prior to enrollment or during the intervention;
• consumption of greater than 1 sugar sweetened beverage per day prior to enrollment

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Metabolic Solutions Inc.: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mount Sinai Morningside

New York, New York, 10025, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Fatty Liver

Interventions

Fructose; Glucose

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Ryan Walker

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ryan Walker, PhD

CONTACT

212-824-7088; ryan.walker@mssm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: All participants undergo both treatment arms but will be blinded to the order.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The study will be a double-blinded (participants and select study personnel), randomized controlled crossover dietary intervention design.

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 26, 2024
• Study Start: October 8, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: December 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose. To achieve aims in the approved proposal. Proposals should be directed to ryan.walker@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years.

Locations

US (1)