Cranberry Ingestion and Cycling Related Immunity and Inflammation
Condition: Inflammatory Response; Metabolic Disturbance; Immune Suppression
MeSH terms: Inflammation
Study type: Interventional

Summary: 
      This is a randomized, crossover clinical trial with 25 male and female cyclists. Study
      participants will ingest polyphenol-rich cranberry juice or placebo juice for 4 weeks under
      double-blinded procedures, and then crossover to the opposite supplement. The primary
      objective of this study is to examine the efficacy of 4-weeks ingestion of cranberry juice in
      moderating exercise-induced inflammation, immune dysfunction, and muscle damage. Outcome
      measures will include global proteiomics, oxylipins, and cytokines.
    

Detailed description: 
      RESEARCH DESIGN: Subjects will come to the lab for orientation/baseline testing, pre-and
      post-supplementation (4 weeks cranberry ingestion compared to water alone) blood, stool, and
      urine sample collections with 3-d food records, two 2.25 h cycling sessions, and additional
      lab visits to provide 1-day 7:00 am recovery blood and saliva samples) (thus 7 total lab
      visits). The total amount of time subjects will be asked to volunteer for this study is about
      16 hours at the Human Performance Laboratory (over a 10-week period).

      1.A. Orientation/Baseline Testing (Visit #1) After voluntarily signed IRB-approved consent
      forms, study participants will be tested for maximal aerobic capacity (VO2max) during a
      graded, cycling test with continuous metabolic monitoring with the Cosmed CPET metabolic
      device (Cosmed, Rome, Italy). Body composition will be measured with the seca BIA and Bod Pod
      body composition analyzer (Life Measurement, Concord, CA). Demographic and training histories
      will be acquired with questionnaires. 3-day food records, 24-h urine collection kits, and
      stool collection kits will be supplied with thorough instructions.

      B. Pre-Supplementation Lab Visit #2 and 4-Week Cranberry Supplementation Protocol: Four weeks
      prior to the first cycling session, subjects will report to the Human Performance Laboratory
      at approximately 7:00-8:00 am. DOMS and POMS questionnaires will be administered. To assess
      potential adverse effects, a symptom inventory will be conducted using a 4-week retrospective
      questionnaire (before and after the 4-week supplementation period). Blood and saliva samples
      will be collected in an overnight fasted state to coincide with the same time of the day for
      the post-supplementation blood draw. Urine samples, stool samples, and 3-d food records will
      be turned in. A 4-week supply of cranberry juice or placebo will be given to the
      participants, with instructions to consume 4 fl. Oz. each with the first and last meals of
      the day (8 fl. Oz. per day for 4 weeks). Subjects will be instructed to store and then bring
      the cranberry and placebo beverage containers to their next lab visit (to verify compliance).
      Subjects will be given a 10-week log book to record daily whether or not they are sick and
      the severity of their symptoms.

      C. 2.25 h Cycling Session (Lab Visit #3): During the 3-day period prior to the 2.25-h cycling
      session, subjects will taper exercise training and ingest a moderate-carbohydrate diet using
      a food list restricting high fat foods, visible fats, and polyphenols. Subjects will record
      all food and beverage intake during the 3-day period, with macro- and micro-nutrient intake
      assessed using the Food Processor dietary analysis software system (ESHA Research, Salem,
      OR). We will also measure total flavonoid intake (and 6 flavonoid subgroups) using the USDA
      flavonoid database that we have incorporated into the Food Processor database (9). Study
      participants will report to the Human Performance Lab in an overnight fasted state, turn in
      urine and stool samples, provide blood and saliva samples, ingest 1 cup cranberry with 1 cup
      of water, or 1 cup of water alone, and then cycle 2.25 h at high intensity (70% VO2max) while
      ingesting water alone (3 ml/kg every 15 minutes). A sweat patch will be applied to the lower
      back before exercise begins and then taken off immediately after the exercise bout is
      complete (https://www.epicorebiosystems.com/gx-sweat-patch/). Blood and saliva samples will
      be collected at 0 h, 1.5 h, 3.0 h, and 24 h post-exercise.

      Testing protocol during the lab sessions with the 2.25-h run session:

        1. 7:00 am: Provide blood and saliva samples, delayed onset of muscle soreness (DOMS)
           rating (1-10 scale), profile of mood states ratings (POMS), and turn in the 24-h urine
           sample, stool sample, and 3-day food record. Fill in the 4-week retrospective symptom
           log.

        2. 7:10 am: Ingest 4 fl. Oz. cranberry or 4 fl. Oz. placebo. A sweat patch will be applied
           to the lower back.

        3. 7:30 am: Start the 2.25 h cycling session. Subjects will cycle on lab trainers at 70%
           VO2max (~marathon race pace) for 2.25 hours. Oxygen consumption, carbon dioxide
           production, respiratory exchange ratio, and ventilation will be measured using the
           Cosmed Quark CPET metabolic cart after 15 minutes and then every 30 minutes. Subjects
           will consume 3 ml/kg water every 15 min. No other beverage or food containing energy or
           nutrients will be allowed during the 2.25-h cycling sessions.

        4. ~10:00 am to 1:00 pm: The sweat patch will be removed. Blood and saliva samples will be
           taken via venipuncture immediately after completing the cycling session, and then 1.5-h
           and 3.0-h post-exercise. Subjects will be allowed to shower and change clothes. The DOMS
           and POMS questionnaires will be administered each time blood and saliva samples are
           collected. Subjects will ingest no food or beverage other than water (7 ml/kg during the
           1.5 h post-exercise period). After the 1.5 h post-exercise blood draw, subjects will
           consume Boost (8 kcal per kilogram of body weight). Another blood sample will be
           collected 3-h post-exercise. Afterwards, subjects will be allowed to leave the lab with
           instructions to adhere to the food list requirements, and to keep exercise training
           moderate.

        5. 7:00 am, next morning: 24-h blood sample and DOMS and POMS ratings (Lab visit #4).

      D. Washout/Crossover/Repeat Subjects will engage in a 4-week washout period without the
      cranberry supplements, crossover to the opposite treatment arm, and then repeat all
      procedures (Lab visits #5,6,7).
    

Intervention name(s): Cranberry Juice; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 100% cranberry juice; Placebo juice
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized treatment, double blinded procedures, crossover
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Cranberries; exercise; immune function; oxylipins; proteomics