Effect of Flavonoids on Gut Permeability in Cyclists

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.

Study Overview

• Status: Completed
• Conditions: Gut Permeability, Gut Inflammation
• Intervention / Treatment: Drug: Low flavonoid beverage; Drug: High flavonoid beverage

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Logan, Utah, United States, 84322
      • Center for Human Nutrition Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Low flavonoid beverage; Subjects will consume 310 milliliters per day of a dairy-based, low flavonoid, sports nutrition recovery beverage 14 days.	Drug: Low flavonoid beverage; 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.
Active Comparator: High flavonoid beverage; Subjects will consume 310 milliliters per day of a dairy-based, high flavonoid, sports nutrition recovery beverage 14 days.	Drug: High flavonoid beverage; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Three weeks
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.	Three weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal calprotectin by ELISA	Secondary endpoint for intestinal inflammation. Calprotectin is measured in fecal samples by enzyme-linked immunosorbent assay.	Three weeks
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.	Three weeks
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.	Three weeks
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.	Three weeks
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.	Three weeks
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.	Three weeks
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.	One Day
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.	One Day

Collaborators and Investigators

• Sponsor: Utah State University
• Investigators: Principal Investigator: Robert E Ward, PhD, Nutrition, Dietetics and Food Sciences, Utah State University

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2018
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 1010820

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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