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

NCT03339245 | Completed Results

• 1 other identifier: PHO-0956
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Alcoholic Fatty Liver Disease; Obesity

Keywords

obesity; fructose; glucose; fecal microbiota; intestinal permiability; fecal metabolites

Outcome Measures

Primary Outcomes (1)

• Difference in the Distribution of Fecal Microbiota in Each Participant

  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

Study Arms (2)

Glucose, Then Fructose

EXPERIMENTAL

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); Other: Glucose Solution (75 grams)

Fructose, Then Glucose

EXPERIMENTAL

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); Other: Glucose Solution (75 grams)

Interventions

Fructose Solution (75 Grams) OTHER

Fructose given in divided doses at breakfast and dinner.

Fructose, Then Glucose; Glucose, Then Fructose

Glucose Solution (75 grams) OTHER

Glucose given in divided doses at breakfast and dinner.

Also known as: Dextrose

Fructose, Then Glucose; Glucose, Then Fructose

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rockefeller University: lead
• Weill Medical College of Cornell University: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

The Rockefeller University

New York, New York, 10065, United States

Location

Related Publications (4)

• Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004 Dec;40(6):1387-95. doi: 10.1002/hep.20466.

  PMID: 15565570 BACKGROUND

• Luther J, Garber JJ, Khalili H, Dave M, Bale SS, Jindal R, Motola DL, Luther S, Bohr S, Jeoung SW, Deshpande V, Singh G, Turner JR, Yarmush ML, Chung RT, Patel SJ. Hepatic Injury in Nonalcoholic Steatohepatitis Contributes to Altered Intestinal Permeability. Cell Mol Gastroenterol Hepatol. 2015 Mar;1(2):222-232. doi: 10.1016/j.jcmgh.2015.01.001.

  PMID: 26405687 BACKGROUND

• Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W, McGahan JP, Seibert A, Krauss RM, Chiu S, Schaefer EJ, Ai M, Otokozawa S, Nakajima K, Nakano T, Beysen C, Hellerstein MK, Berglund L, Havel PJ. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest. 2009 May;119(5):1322-34. doi: 10.1172/JCI37385. Epub 2009 Apr 20.

  PMID: 19381015 BACKGROUND

• Boursier J, Mueller O, Barret M, Machado M, Fizanne L, Araujo-Perez F, Guy CD, Seed PC, Rawls JF, David LA, Hunault G, Oberti F, Cales P, Diehl AM. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology. 2016 Mar;63(3):764-75. doi: 10.1002/hep.28356. Epub 2016 Jan 13.

  PMID: 26600078 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity

Interventions

Glucose

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates

Results Point of Contact

• Title: Dr. Peter R Holt
• Organization: The Rockefeller University

holtp@rockefeller.edu

212-327-7706

Study Officials

• Peter Holt, MD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 13, 2017
• Study Start: December 5, 2017
• Primary Completion: October 2, 2018
• Study Completion: October 2, 2018
• Last Updated: March 26, 2021
• Results First Posted: March 26, 2021

Record last verified: 2021-03

Locations

US (1)