Effect of Combined Exercise, Heat, and Quercetin Supplementation on Whole Body Stress Response
Condition: Heat Acclimation and Thermotolerance
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Quercetin; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 2g/d dietary quercetin supplementation, 1g taken am; 1g taken pm; Placebo, performed on same subjects as Quercetin Arm, used to compare results between conditions
Intervention MeSH terms: Quercetin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: thermotolerance; heat acclimation; quercetin; exertional heat illness; gastrointestinal barrier permeability