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

Not Applicable

Completed

Conditions: Obesity
Non-Alcoholic Fatty Liver Disease

Interventions: Other: Fructose Solution (75 Grams)
Other: Glucose Solution (75 grams)

Registration Number: NCT03339245

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Glucose, Then Fructose	Fructose Solution (75 Grams)	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.
Glucose, Then Fructose	Glucose Solution (75 grams)	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.
Fructose, Then Glucose	Fructose Solution (75 Grams)	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.
Fructose, Then Glucose	Glucose Solution (75 grams)	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.

Primary Outcome Measures

Name	Time	Method
Difference in the Distribution of Fecal Microbiota in Each Participant	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.

Secondary Outcome Measures