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

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ClinicalTrials.gov Identifier: NCT03339245
Recruitment Status : Completed
First Posted : November 13, 2017
Last Update Posted : February 5, 2019
Sponsor:
Collaborators:
Weill Medical College of Cornell University
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Peter Holt, MD, Rockefeller University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Non-Alcoholic Fatty Liver Disease Obesity Other: Fructose Solution (75 Grams) Other: Glucose Solution (75 grams) Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double blind
Primary Purpose: Basic Science
Official Title: Effects of Dietary Fructose on Gut Microbiota and Fecal Metabolites in Obese Men and Postmenopausal Women: A Pilot Study
Actual Study Start Date : December 5, 2017
Actual Primary Completion Date : October 2, 2018
Actual Study Completion Date : October 2, 2018


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 Name: 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 Name: Dextrose




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   45 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03339245


Locations
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United States, New York
The Rockefeller University
New York, New York, United States, 10065
Sponsors and Collaborators
Rockefeller University
Weill Medical College of Cornell University
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Peter Holt, MD Rockefeller University

Publications:
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Responsible Party: Peter Holt, MD, Senior Research Associate, Rockefeller University
ClinicalTrials.gov Identifier: NCT03339245     History of Changes
Other Study ID Numbers: PHO-0956
First Posted: November 13, 2017    Key Record Dates
Last Update Posted: February 5, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peter Holt, MD, Rockefeller University:
obesity
fructose
glucose
fecal microbiota
intestinal permiability
fecal metabolites

Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Pharmaceutical Solutions