Gut Permeability, Gut Inflammation
Conditions
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.
Interventions
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.
DRUGHigh 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.
Sponsors
Utah State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary lactulose:mannitol ratio by gas chromatography | Three weeks | 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 | Three weeks | Marker of gut wall integrity. i-FABP is measure by enzyme-linked immunosorbent assay in plasma of subjects after the time trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum soluble tumor necrosis factor (TNFa) by ELISA | Three weeks | 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 | Three weeks | 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 | Three weeks | One of four secondary endpoints for systemic inflammation. The cytokine, IL-10, is measured in plasma by enzyme-linked immunosorbent assay. |
| Fecal calprotectin by ELISA | Three weeks | Secondary endpoint for intestinal inflammation. Calprotectin is measured in fecal samples by enzyme-linked immunosorbent assay. |
| Distance ridden in time trial | One Day | 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. | One Day | 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. |
| Serum endotoxin by ELISA. | Three weeks | One of four secondary endpoint for systemic inflammation. The bacterial cell wall product is measured in plasma by enzyme-linked immunosorbent assay. |
| Urinary sucralose:mannitol ratio by gas chromatography | Three weeks | 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. |
Countries
United States
Outcome results
None listed