High Fructose Diet, the Gut Microbiome, and Metabolic Health

Part of paid clinical trials in New York, New York.

Sponsor
Icahn School of Medicine at Mount Sinai
Study ID
NCT06329544
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
25 Years - 45 Years
Healthy Volunteers
Accepted

Interventions

  • Fructose — DIETARY_SUPPLEMENT
    12-day isocaloric weight-maintaining high fructose diet (25% total calories from added fructose)
  • glucose — DIETARY_SUPPLEMENT
    12-day isocaloric weight-maintaining high glucose diet (25% total calories from added glucose)

Study Details

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. Determine the relationships between high fructose consumption, the gut microbiome and metabolic risk. 2. Characterize the causal role(s) that fructose-induced alterations to the gut microbiome have on metabolic risk using a germ-free mouse model. The research team will measure 1) microbiota community structure and function via metagenomic sequencing of stool, 2) fecal metabolites via targeted and untargeted metabolomics, 3) anthropometrics, 4) insulin resistance, serum markers of T2D risk and inflammatory cytokines, 5) fecal microbial carbohydrate oxidation capacity and 6) liver fat via MRI elastography. The research team will use novel statistical approaches, including Distributed Lag Modeling, to understand the complex relationships between diet, the microbiome, metabolites and health outcomes. The research team will then conduct controlled dietary interventions and fecal microbiome transplantation studies in germ-free mice. Donor fecal samples from human participants in both the glucose and fructose arms of the clinical intervention will be transplanted into germ-free and colonized mice to establish a causal relationship between fructose-induced changes to the gut microbiome, liver fat and metabolic and inflammatory changes known to increase risk for T2D. The research team aims to comprehensively assess the structural and functional changes to the gut microbiome brought about by a high fructose diet. Determining the impact of excess fructose on the microbiome will help identify novel means by which fructose contributes to metabolic disease risk. In addition to identifying strategies to improve metabolic health in adults, data from this proposal could help inform targeted approaches to mitigate future disease risk in vulnerable populations that consume high levels of fructose, such as children.

Key Dates

Start date
Oct 8, 2024
Status verified
Nov 2025
Primary completion
Aug 31, 2028
Completion
Aug 31, 2028

Study Design

Enrollment
30 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION

Arms

  • Experimental: Fructose Dietary then Glucose Dietary
    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.
  • Experimental: Glucose Dietary then Fructose Dietary
    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.

Primary Outcome Measure

Liver proton density fat fraction (PDFF) [ Time Frame: year 3 ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Mount Sinai MorningsideNew YorkNew York10025
Ryan Walker (PRINCIPAL_INVESTIGATOR)

Find similar trials in New York, NY

By condition
Obesity / overweightType 2 diabetes
By specialty
EndocrinologyMetabolic healthWeight loss
By research site
Mount Sinai Morningside· New York, NY

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