Effects of Dietary Fructose on Gut Microbiota and Fecal Metabolites in Obese Men and Postmenopausal Women: A Pilot Study

March 25, 2021 updated by: Rockefeller University

Non alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function tests in the U.S. (Browning, et al., 2004), ranging from steatosis to end-stage liver disease. Fructose ingestion by the American public has steadily increased since the 1980's, and with it increases in NAFLD, fatty liver hepatitis (NASH), diabetes, obesity, and cardiovascular disease. Foods and beverage in the U.S. are typically sweetened with sucrose (50% glucose and 50% fructose) or high fructose corn syrup (45-58% glucose and 42-55% fructose) (Stanhope, et al., 2009). Research into the role that added fructose plays in the emerging chronic health issues is necessary to affect public policy and provide the connection between fructose and the increasing incidence of these co-morbidities.

There is evidence that gut bacteria contribute to a range of human diseases including those of the liver and gastrointestinal tract. Dietary fructose has been suggested to play a role in the development of these diseases and has been shown to alter gut microbes in animals. If the investigators find that dietary fructose alters bacteria in the human gut, this would suggest a potential targetable link between high fructose diet and disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Non- alcoholic fatty liver disease (NAFLD) occurs in 30% of the adult US population (Luther, J., et al., 2015). Eating large amounts of fructose (a dietary sugar) increases liver fat accumulation and worsens NAFLD. In addition, fructose consumption has been shown to greatly increase triglycerides(fat) in the blood after meals, increasing the risk of heart disease,(Stanhope,et al., 2009) insulin resistance and diabetes. Current theories on liver disease caused by consuming fructose focuses on changes in the breakdown of fat by the liver. In experimental animals, fructose feeding changes the bacteria population (microbiota) in the gut, causes NAFLD and NASH, and increases leaking of toxins from the intestine (intestinal permeability) to the blood stream resulting in inflammation.

In humans, fructose consumption rapidly increases liver fat. However, changes in gut microbiota have not been studied. The proposed study will compare the addition of fructose or glucose to the study subjects' usual diet in a crossover design. They will not know which sugar they are receiving.

The Investigators plan to study postmenopausal, moderately obese but healthy women, and moderately obese but healthy men (age 45-70 years) to find out the effect of fructose verses glucose on the bacteria in their stool and inflammation in the bowel. The Investigators hypothesize that adding fructose to the participant's usual diet, compared to glucose, will change stool bacteria composition and the products that the bacteria produce, which may increase intestinal leakage, and increase markers of inflammation in the stool and blood due to this leakage. These changes may contribute to fructose -induced liver disease.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • The Rockefeller University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Post menopausal female, last menstrual period at least 24 months ago OR male
  • Age 45-70
  • Willing to consume usual diet with either fructose or glucose added during (2) 16-18 day inpatient stays
  • Willing to consume usual diet during 2 week wash-out period at home
  • BMI 30.0-39.9
  • Willingness not to travel long distances while on study, including wash-out period
  • Willingness not to be exposed to new pets while on study including wash-out period

Exclusion Criteria:

  • Fasting serum triglycerides >200mg/dl
  • Fasting blood glucose >126mg/dl
  • Renal function tests >2x Upper limit of normal
  • Liver Function Tests > 1.5x Upper limit of normal
  • Currently on statins
  • Daily use of a cathartic
  • Broad spectrum antibiotic use within the past 45 days
  • Currently on proton pump inhibitor
  • Currently on insulin or oral hypoglycemic agents
  • Active viral Hepatitis
  • Chronic constipation
  • Inflammatory bowel disease
  • Chronic diarrhea
  • GI resection
  • Any evidence of cardiovascular disease on EKG
  • History of cardiovascular disease such as coronary artery disease, Coronary Artery Bypass Graft, valve replacement, Myocardial Infarction, stroke / Transient Ischemic attack.
  • History of macronutrient malabsorption
  • Current smoker. Stopped < 3 months ago.
  • Daily alcohol intake equal to 1.5 oz of 40 proof alcohol.
  • HIV positive
  • Any medical, psychological or social condition that, in the opinion of the Investigator, would jeopardize the health or well-being of the participant during any study procedures or the integrity of the data
  • Persons taking probiotics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Glucose, Then Fructose
Participants first receive Glucose Solution (75 grams) from Day 3 through Day 16 of an inpatient stay with usual diet. After a 2-3 week washout period, they will then receive Fructose Solution (75 Grams) from Day 3 through Day 16 on a second inpatient stay with usual diet.
Other: Fructose Solution (75 Grams)
Fructose given in divided doses at breakfast and dinner.
Other: Glucose Solution (75 grams)
Glucose given in divided doses at breakfast and dinner.
Other Names:
  • Dextrose
Experimental: Fructose, Then Glucose
Participants first receive Fructose Solution (75 grams) from Day 3 through Day 16 of an inpatient stay with usual diet. After a 2-3 week washout period, they will then receive Glucose Solution (75 grams) from Day 3 through Day 16 on a second inpatient stay with usual diet.
Other: Fructose Solution (75 Grams)
Fructose given in divided doses at breakfast and dinner.
Other: Glucose Solution (75 grams)
Glucose given in divided doses at breakfast and dinner.
Other Names:
  • Dextrose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in the Distribution of Fecal Microbiota in Each Participant
Time Frame: assessed at Day 16 of each intervention, up to 64 days
Difference in the distribution of fecal microbiota in each participant, between the fructose versus glucose supplemented diet arms of the study, as measured at the end of each intervention.
assessed at Day 16 of each intervention, up to 64 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rockefeller University

Collaborators

National Institutes of Health (NIH)
Weill Medical College of Cornell University

Investigators

  • Principal Investigator: Peter Holt, MD, Rockefeller University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 5, 2017

Primary Completion (Actual)

October 2, 2018

Study Completion (Actual)

October 2, 2018

Study Registration Dates

First Submitted

November 7, 2017

First Submitted That Met QC Criteria

November 7, 2017

First Posted (Actual)

November 13, 2017

Study Record Updates

Last Update Posted (Actual)

March 26, 2021

Last Update Submitted That Met QC Criteria

March 25, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PHO-0956

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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