Effect of Flavonoids on Gut Permeability in Cyclists
Primary Purpose
Gut Permeability, Gut Inflammation
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Low flavonoid beverage
High flavonoid beverage
Sponsored by

About this trial
This is an interventional prevention trial for Gut Permeability, Gut Inflammation
Eligibility Criteria
Inclusion Criteria:
- Male or female of any race or ethnicity between 18 to 49 years of age
- Competed in a road race or triathlon in past 12 months
- Free of chronic disease and GI conditions
- Train at least 3 times per week, 1 hour at a time on average
- Willing to prepare and consume provided pre-workout beverage daily
- Maintain weight (no more/less than 5 kg change)
- Willing to avoid consumption of high flavonoid foods/supplements, large dose vitamin and mineral supplements, and NSAIDs or other medications known to affect inflammation during study period
- Willing to provide urine, stool, and blood samples
Exclusion Criteria:
- Age <18 or >50 years
- Medical history of heart disease, hypertension, diabetes, Crohn's disease, IBS, colitis, celiac disease, inflammatory or autoimmune disease, and lactose intolerance
- Uncontrolled hypertension: diastolic blood pressure >95 mm Hg or systolic blood pressure >160 mm Hg
- For women: pregnancy, breast feeding or postpartum <6 months
- Food allergies or restrictions to treatment/placebo beverages
- Chronic use of NSAIDs
- Consumption of flavonoid supplements <1 month prior to study start
- Antibiotic use <3 months prior to study start
- Other conditions (medical, psychiatric, or behavioral) that may present a safety hazard to the participant or interfere with study participation, as determined by the principal investigators
Sites / Locations
- Center for Human Nutrition Studies
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Low flavonoid beverage
High flavonoid beverage
Arm Description
Subjects will consume 310 milliliters per day of a dairy-based, low flavonoid, sports nutrition recovery beverage 14 days.
Subjects will consume 310 milliliters per day of a dairy-based, high flavonoid, sports nutrition recovery beverage 14 days.
Outcomes
Primary Outcome Measures
Urinary lactulose:mannitol ratio by gas chromatography
Measure of gut permeability from mouth to end of small intestine. Ratio of urinary lactulose to mannitol after subject consumes a beverage containing these sugars. Sugars in urine are measured by gas chromatography with flame ionization detection.
Plasma intestinal fatty acid binding protein (i-FABP) by ELISA
Marker of gut wall integrity. i-FABP is measure by enzyme-linked immunosorbent assay in plasma of subjects after the time trial.
Secondary Outcome Measures
Fecal calprotectin by ELISA
Secondary endpoint for intestinal inflammation. Calprotectin is measured in fecal samples by enzyme-linked immunosorbent assay.
Urinary sucralose:mannitol ratio by gas chromatography
Secondary measure of gut permeability from mouth to end of colon. Ratio of urinary lactulose to mannitol after subject consumes a beverage containing these sugars. Sugars in urine are measured by gas chromatography with flame ionization detection.
Serum soluble tumor necrosis factor (TNFa) by ELISA
One of four secondary endpoints for systemic inflammation. The cytokine, TNFa, is measured in plasma by enzyme-linked immunosorbent assay.
Serum soluble interleukin-6 (IL-6) by ELISA
One of four secondary endpoints for systemic inflammation. The cytokine, IL-6, is measured in plasma by enzyme-linked immunosorbent assay.
Serum soluble interleukin-10 by ELISA
One of four secondary endpoints for systemic inflammation. The cytokine, IL-10, is measured in plasma by enzyme-linked immunosorbent assay.
Serum endotoxin by ELISA.
One of four secondary endpoint for systemic inflammation. The bacterial cell wall product is measured in plasma by enzyme-linked immunosorbent assay.
Distance ridden in time trial
Subjects will complete a 15m time trial on a bike after each dietary intervention. The distance covered in each time trial will be measured by the computer on the exercise bike.
Rating of perceived exertion by questionnaire.
Subjects will complete a 15m time trial on a bike after each dietary intervention. This measure is a subjective measure of the difficulty of the work. Subjects will provide the ratings orally during the time trial.
Full Information
NCT ID
NCT03427879
First Posted
January 30, 2018
Last Updated
February 23, 2021
Sponsor
Utah State University
1. Study Identification
Unique Protocol Identification Number
NCT03427879
Brief Title
Effect of Flavonoids on Gut Permeability in Cyclists
Official Title
Effect of Flavonoids on Gut Permeability in Cyclists
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
September 14, 2018 (Actual)
Primary Completion Date
May 15, 2019 (Actual)
Study Completion Date
July 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Utah State University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this investigation is to test the hypothesis that chronic supplementation with a dairy-based beverage containing a mixture of blueberry, green tea, and cocoa flavonoids (non-nutritive natural plant compounds) will ameliorate exercise-related changes in gut permeability and inflammation. In a previous feeding study in humans, (NCT02728570) a high flavonoid diet (flavonoids at 340 mg/1000kcal) was effective in mitigating gut permeability and inflammation in overweight and obese adults compared to a low flavonoid diet (10mg/1000 kcal). To test this hypothesis, 20 trained cyclists will complete a randomized crossover study with supplementation for 2 weeks with a dairy-based sports beverage containing either a high flavonoid (approximately 620 mg) or low flavonoid (approximately 5mg) beverage. After the two week intervention, cyclists will complete a 1 hour cycling trial (45 min at 65% VO2 max then 15 minute time trial). The primary endpoints will be gut permeability as measured by plasma intestinal fatty acid binding protein (I-FABP) and the differential sugar test. Secondary endpoints will include gut inflammation (measured via fecal calprotectin), plasma cytokines (IL-6, IL-10 and TNFα) and plasma LPS. In addition, the distance completed in the time trial is a secondary endpoint.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gut Permeability, Gut Inflammation
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low flavonoid beverage
Arm Type
Placebo Comparator
Arm Description
Subjects will consume 310 milliliters per day of a dairy-based, low flavonoid, sports nutrition recovery beverage 14 days.
Arm Title
High flavonoid beverage
Arm Type
Active Comparator
Arm Description
Subjects will consume 310 milliliters per day of a dairy-based, high flavonoid, sports nutrition recovery beverage 14 days.
Intervention Type
Drug
Intervention Name(s)
Low flavonoid beverage
Intervention Description
A low flavonoid, sports nutrition recovery beverage will be prepared from milk (78%), sugar (8.6%), maltodextrin (8.6%), placebo blueberry powder (2.4%), alkalized cocoa powder (1.6%), and whey protein isolate (0.6%). The beverage will contain approximately 5mg flavonoids per serving.
Intervention Type
Drug
Intervention Name(s)
High flavonoid beverage
Intervention Description
A high flavonoid, sports nutrition recovery beverage will be prepared from milk (78%), sugar (8.6%), maltodextrin (8.6%), blueberry powder (2.4%), cocoa powder (1.6%), green tea extract (0.1%) and whey protein isolate (0.6%). The beverage will contain approximately 620 mg flavonoids per serving.
Primary Outcome Measure Information:
Title
Urinary lactulose:mannitol ratio by gas chromatography
Description
Measure of gut permeability from mouth to end of small intestine. Ratio of urinary lactulose to mannitol after subject consumes a beverage containing these sugars. Sugars in urine are measured by gas chromatography with flame ionization detection.
Time Frame
Three weeks
Title
Plasma intestinal fatty acid binding protein (i-FABP) by ELISA
Description
Marker of gut wall integrity. i-FABP is measure by enzyme-linked immunosorbent assay in plasma of subjects after the time trial.
Time Frame
Three weeks
Secondary Outcome Measure Information:
Title
Fecal calprotectin by ELISA
Description
Secondary endpoint for intestinal inflammation. Calprotectin is measured in fecal samples by enzyme-linked immunosorbent assay.
Time Frame
Three weeks
Title
Urinary sucralose:mannitol ratio by gas chromatography
Description
Secondary measure of gut permeability from mouth to end of colon. Ratio of urinary lactulose to mannitol after subject consumes a beverage containing these sugars. Sugars in urine are measured by gas chromatography with flame ionization detection.
Time Frame
Three weeks
Title
Serum soluble tumor necrosis factor (TNFa) by ELISA
Description
One of four secondary endpoints for systemic inflammation. The cytokine, TNFa, is measured in plasma by enzyme-linked immunosorbent assay.
Time Frame
Three weeks
Title
Serum soluble interleukin-6 (IL-6) by ELISA
Description
One of four secondary endpoints for systemic inflammation. The cytokine, IL-6, is measured in plasma by enzyme-linked immunosorbent assay.
Time Frame
Three weeks
Title
Serum soluble interleukin-10 by ELISA
Description
One of four secondary endpoints for systemic inflammation. The cytokine, IL-10, is measured in plasma by enzyme-linked immunosorbent assay.
Time Frame
Three weeks
Title
Serum endotoxin by ELISA.
Description
One of four secondary endpoint for systemic inflammation. The bacterial cell wall product is measured in plasma by enzyme-linked immunosorbent assay.
Time Frame
Three weeks
Title
Distance ridden in time trial
Description
Subjects will complete a 15m time trial on a bike after each dietary intervention. The distance covered in each time trial will be measured by the computer on the exercise bike.
Time Frame
One Day
Title
Rating of perceived exertion by questionnaire.
Description
Subjects will complete a 15m time trial on a bike after each dietary intervention. This measure is a subjective measure of the difficulty of the work. Subjects will provide the ratings orally during the time trial.
Time Frame
One Day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male or female of any race or ethnicity between 18 to 49 years of age
Competed in a road race or triathlon in past 12 months
Free of chronic disease and GI conditions
Train at least 3 times per week, 1 hour at a time on average
Willing to prepare and consume provided pre-workout beverage daily
Maintain weight (no more/less than 5 kg change)
Willing to avoid consumption of high flavonoid foods/supplements, large dose vitamin and mineral supplements, and NSAIDs or other medications known to affect inflammation during study period
Willing to provide urine, stool, and blood samples
Exclusion Criteria:
Age <18 or >50 years
Medical history of heart disease, hypertension, diabetes, Crohn's disease, IBS, colitis, celiac disease, inflammatory or autoimmune disease, and lactose intolerance
Uncontrolled hypertension: diastolic blood pressure >95 mm Hg or systolic blood pressure >160 mm Hg
For women: pregnancy, breast feeding or postpartum <6 months
Food allergies or restrictions to treatment/placebo beverages
Chronic use of NSAIDs
Consumption of flavonoid supplements <1 month prior to study start
Antibiotic use <3 months prior to study start
Other conditions (medical, psychiatric, or behavioral) that may present a safety hazard to the participant or interfere with study participation, as determined by the principal investigators
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert E Ward, PhD
Organizational Affiliation
Nutrition, Dietetics and Food Sciences, Utah State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Human Nutrition Studies
City
Logan
State/Province
Utah
ZIP/Postal Code
84322
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Effect of Flavonoids on Gut Permeability in Cyclists
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