Effect of Combined Exercise, Heat, and Quercetin Supplementation on Whole Body Stress Response

The purpose of this study is to determine whether dietary quercetin supplementation effects thermotolerance and heat acclimation in human subjects exposed to exercise/heat stress.

Specific Aim I. To determine if quercetin in combination with repeated bouts of thermally stressful exercise will impact intestinal barrier function. The investigators will examine urinary lactulose excretion, plasma endotoxin,plasma quercetin, inflammatory cytokines (TNF-a \& Il-6), anti-inflammatory cytokines (Il-10), and HSP70 and HSF-1 content of peripheral blood mononuclear cells.

Specific Aim II. To determine whether quercetin's suppresses the ability of human subjects to acclimate to exercise/heat stress. The investigators will examine body temperatures, heart rates, physiological strain, sweat and plasma volume responses to standardized heat tolerance tests.

Overall Protocol:

This study will involve a repeated-measures design (2 conditions) in which subjects will perform exercise in the heat. Each condition will begin with an Intestinal Permeability Measurement (IP1), where subjects will be admitted to the General Clinical Research Center (GCRC), drinking a test solution and collecting their urine for 8 hours to measure intestinal integrity prior to heat stress. This will be followed by a Heat Tolerance Trial (HT1: 50min exercise at 50% VO2max in environmental chamber controlled at 56oC, 20%RF), used as a baseline measurement of subject's capacity to work in the heat. Following HT1 each subject will perform 7 Days of Heat Acclimation (HA)exercise (controlled hyperthermia design, each subject will elevate core temperature \>39oC in 50min during 50 minutes of exercise in environmental chamber controlled at 56oC, 20%RF; rest 10 min in environmental chamber; then perform another 50min of exercise at this elevated core temperature). On days 1 and 7 of HA subjects will follow exercise by performing additional Intestinal Permeability Measurements, providing pre (IP2) and post acclimation (IP3) measurements of intestinal permeability. Day 6 of HA will provide a posttest measurement of subjects' capacity to work in the heat, and will be synonymous with Heat Tolerance Trial 2 (HT2).

Subjects will take quercetin during the seven days of HA in one condition, and placebo in the other. At least 1 month must elapse before a subject will be allowed to repeat the opposite condition. The order will be balanced (half will take quercetin first, the other half placebo). This will be a double blinded study. Neither the investigators nor the subjects will know whether a HA involves quercetin or placebo.

Due to the possibility of outside factors causing variations in intestinal permeability over the course of the study, IP1 will always be used as a baseline condition, with IP2 and IP3 being scored relative (as percent change) to the first. Subjects will never be supplemented in IP1, as this might affect basal measurements of permeability. However, because quercetin supplementation may only exert a transient effect on intestinal permeability, subjects will always be supplemented (with either placebo or quercetin, according to condition) in IP2 and IP3.

In all conditions, subjects will be required to follow guidelines on diet and exercise. They will be instructed to avoid caffeine, alcohol, and to stay well hydrated. They will be instructed to avoid exercise that is not directly outlined by the experiment (see attached). Their meals will be provided by the GCRC to ensure adequate nutrition and to avoid high dietary levels of quercetin. We are currently working with BioNutrition on this menu. To ensure compliance with this diet, subjects will fill out a food diary.

Eligibility Criteria:
Inclusion Criteria:

* Healthy: 1 or less CV risk factor. Positive risk factors include:

  * Family history
  * Current cigarette smoker or quit within the previous 6 months
  * Hypertension (\>140/90 mmHg) or on antihypertensive medication
  * Impaired fasting glucose (\>110 mg/dl)
  * Dyslipidemia (LDL\>130 mg/dl;HDL\<40 mg/dl, total \>200 mg/dl)
  * Low VO2 peak: \<40ml/kg/min
  * Overfatness(BMI\>30 kg/m2 and/or body fat \> 25%)
* Male
* 18-39 years of age
* Willing to follow study diet
* Willing to exercise for prescribed time
* Willing to tolerate hot environment
* Willing to avoid external influences (ambient heat, uv exposure, external exercise) for study duration

Exclusion Criteria:

* History of heat illness
* Current NSAID use
* Known gastrointestinal disease
* Illness (physician provide physical before subject begin each condition)