Effect of Dietary Flavonoids on Intestinal Microbiota, Intestinal Inflammation and Metabolic Syndrome

The investigators have hypothesized that dietary flavonoids reduce insulin resistance and subclinical inflammation secondary to reductions in intestinal inflammation and permeability and that these events are mediated through alterations in gut microbiota composition. To test this hypothesis, 30 overweight/obese men and women will be provided two well-controlled diets that are identical in macronutrient content (Protein, 17% en; Fat, 30% en; Carbohydrate, 53% en), but differ markedly in flavonoid content (Low Flavonoid Diet, 10 mg/1000 Kcals; High Flavonoid Diet, 340 mg/1000 Kcals). All meals for both diets will be prepared and fed for 6 weeks each in a randomized cross-over design with endpoints determined in duplicate during the last week of each diet period.

Study Overview

• Status: Completed
• Conditions: Inflammation; Metabolic Syndrome X
• Intervention / Treatment: Other: High Dietary Flavonoids; Other: Low Dietary Flavonoids

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Logan, Utah, United States, 84322-9815
      • Utah State University, Center for Human Nutrition Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI between 25 and 35 kg/m2

Exclusion Criteria:

• Documented presence of atherosclerotic disease;
• Diabetes mellitus
• Uncontrolled hypertension
• Renal, hepatic, endocrine, gastrointestinal or other systemic disease
• For women, pregnancy, breast feeding or postpartum < 6 months
• History of drug or alcohol abuse
• History of depression or mental illness requiring hospitalization within the last 12 months
• Use of antibiotics within the last 6 months
• Multiple food allergies or significant food preferences or restrictions that would interfere with diet adherence
• Chronic use of over-the-counter medication which would interfere with study endpoints including NSAIDS, laxatives and antacids
• Lifestyle or schedule incompatible with the study protocol
• Other medical, psychiatric, or behavioral conditions that in the view of the principal investigator may present a safety hazard to the participant or interfere with study participation or the ability to follow the intervention protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Flavonoids then High Flavonoids; Participants receive a prepared diet with Low Dietary Flavonoids (10 mg of flavonoids/1000 Kcals) for six weeks. After a minimum washout period of 2 weeks, participants receive a prepared diet with High Dietary Flavonoids (340 mg of flavonoids/1000 Kcals) for six weeks.	Other: High Dietary Flavonoids; A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing high levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.; Other: Low Dietary Flavonoids; A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing low levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.
Experimental: High Flavonoids then Low Flavonoids; Participants receive a prepared diet with High Dietary Flavonoids (340 mg of flavonoids/1000 Kcals) for six weeks. After a minimum washout period of 2 weeks, participants receive a prepared diet with Low Dietary Flavonoids (10 mg of flavonoids/1000 Kcals) for six weeks.	Other: High Dietary Flavonoids; A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing high levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.; Other: Low Dietary Flavonoids; A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing low levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal calprotectin	Primary endpoint for intestinal inflammation	6 weeks
Serum C-reactive protein	One of two primary endpoints for systemic inflammation	6 weeks
Serum soluble tumor necrosis factor receptor-1	One of two primary endpoints for systemic inflammation	6 weeks
Serum insulin	Primary endpoint for insulin resistance	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal microbiome composition	Includes relative abundances of operational taxonomic units and assigned taxonomy as well as alpha and beta diversity measurements	6 weeks
Fecal short chain fatty acids	Measure of fecal microbiome metabolic capabilities and includes acetate, propionate, butyrate, valerate and caproate.	6 weeks
Fecal eosinophil protein X	Secondary endpoint for intestinal inflammation	6 weeks
Fecal myeloperoxidase	Secondary endpoint for intestinal inflammation	6 weeks
Intestinal permeability by four sugar differential absorption test	Secondary endpoint for intestinal inflammation	6 weeks
Serum endotoxin	Secondary endpoint for intestinal inflammation	6 weeks
Serum interleukin-6	Secondary endpoint for systemic inflammation	6 weeks
Serum soluble tumor necrosis factor receptor-2	Secondary endpoint for systemic inflammation	6 weeks
Serum fasting glucose	Secondary endpoint for insulin resistance	6 weeks
Calculated Homeostatic Model Assessment-Insulin Resistance	Secondary endpoint for insulin resistance	6 weeks
Serum C-peptide	Secondary endpoint for insulin resistance	6 weeks
Plasma lipids	Secondary endpoint for insulin resistance. Includes LDL-cholesterol, HDL-cholesterol and triglycerides	6 weeks
Blood pressure	Secondary endpoint for insulin resistance. Includes systolic and diastolic blood pressure	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum resistin	Measure of adipocyte inflammation and systemic metabolism	6 weeks
Serum visfatin	Measure of adipocyte inflammation and systemic metabolism	6 weeks
Serum adiponectin	Measure of adipocyte inflammation and systemic metabolism	6 weeks
Serum leptin	Measure of adipocyte inflammation and systemic metabolism	6 weeks
Body weight		6 weeks

Collaborators and Investigators

• Sponsor: Utah State University

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: March 30, 2016
• First Posted (Estimate): April 5, 2016

Study Record Updates

• Last Update Posted (Estimate): April 15, 2016
• Last Update Submitted That Met QC Criteria: April 14, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: flavonoids; insulin resistance; intestinal microbiome; intestinal inflammation; subclinical inflammation; plasma lipids
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Inflammation; Metabolic Syndrome
• Other Study ID Numbers: USU #5483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual data will be deposited into a public repository as the data are published.