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

Sponsor

Utah State University (Other)

Overall Status

Completed

CT.gov ID

NCT02728570

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metabolic Syndrome X Inflammation	Other: High Dietary Flavonoids Other: Low Dietary Flavonoids	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Nov 1, 2013

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

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.

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

Other: Low Dietary Flavonoids

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Serum resistin [6 weeks]
Measure of adipocyte inflammation and systemic metabolism
Serum visfatin [6 weeks]
Measure of adipocyte inflammation and systemic metabolism
Serum adiponectin [6 weeks]
Measure of adipocyte inflammation and systemic metabolism
Serum leptin [6 weeks]
Measure of adipocyte inflammation and systemic metabolism
Body weight [6 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.