Effect of Flavonoids on Gut Permeability in Cyclists

NCT03427879 | Completed Phase 1

• 1 other identifier: 1010820
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Gut Permeability, Gut Inflammation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Fecal calprotectin by ELISA

  Three weeks

• Urinary sucralose:mannitol ratio by gas chromatography

  Three weeks

• Serum soluble tumor necrosis factor (TNFa) by ELISA

  Three weeks

• Serum soluble interleukin-6 (IL-6) by ELISA

  Three weeks

• Serum soluble interleukin-10 by ELISA

  Three weeks

Study Arms (2)

Low flavonoid beverage

PLACEBO COMPARATOR

Subjects will consume 310 milliliters per day of a dairy-based, low flavonoid, sports nutrition recovery beverage 14 days.

Drug: Low flavonoid beverage

High flavonoid beverage

ACTIVE COMPARATOR

Subjects will consume 310 milliliters per day of a dairy-based, high flavonoid, sports nutrition recovery beverage 14 days.

Drug: High flavonoid beverage

Interventions

Low flavonoid beverage DRUG

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.

Low flavonoid beverage

High flavonoid beverage DRUG

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.

High flavonoid beverage

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Utah State University: lead

Study Sites (1)

Center for Human Nutrition Studies

Logan, Utah, 84322, United States

Location

Related Publications (1)

• Kung S, Vakula MN, Kim Y, England DL, Bergeson J, Bressel E, Lefevre M, Ward R. No effect of a dairy-based, high flavonoid pre-workout beverage on exercise-induced intestinal injury, permeability, and inflammation in recreational cyclists: A randomized controlled crossover trial. PLoS One. 2022 Nov 29;17(11):e0277453. doi: 10.1371/journal.pone.0277453. eCollection 2022.

  PMID: 36445874 DERIVED

Study Officials

• Robert E Ward, PhD

  Nutrition, Dietetics and Food Sciences, Utah State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: February 9, 2018
• Study Start: September 14, 2018
• Primary Completion: May 15, 2019
• Study Completion: July 31, 2019
• Last Updated: February 25, 2021

Record last verified: 2021-02

Locations

US (1)