Flavonoid-rich Supplement Influence on the Human Metabolome
Condition: Inflammation
MeSH terms: Inflammation
Study type: Interventional

Summary: 
      This study will measure the effect of ingesting a flavonoid-rich supplement on various
      biomarkers in overweight/obese women during a 12-week period. The flavonoid-rich supplement
      contains a mixture of flavonoids including quercetin, catechins from green tea extract, and
      anthocyanins from bilberry extract, and other food components that facilitate flavonoid
      bioactivity including fish oil, caffeine, and vitamin C.
    

Detailed description: 
      1. The primary objective of this study is to evaluate the effect of ingesting a
           flavonoid-rich supplement on total urine polyphenol concentration and shifts in blood
           metabolites related to flavonoid intake in healthy but overweight/obese
           community-dwelling adults.

        2. Secondary objectives are to determine related effects on measures of inflammation and
           oxidative stress. Studies are mixed regarding the influence of flavonoid supplements on
           traditional biomarkers for inflammation and oxidative stress, and metabolite shifts from
           the metabolomics measurements may provide better insights. Chemistry profiles and
           symptom logs will be compared pre- and post-study between groups to confirm prior safety
           data collected on human participants.

      Hypothesis: Subjects randomized to ingestion of the flavonoid-rich supplement compared to
      placebo will experience an increase in total urine polyphenols concentrations and shifts in
      blood metabolites related to increased flavonoid metabolism. Secondarily, subjects ingesting
      the flavonoid-rich supplement will experience a decrease in systemic inflammation and
      oxidative stress.

      BASELINE TESTING (ASU-NCRC HUMAN PERFORMANCE LAB):

      A. One week before the start of the study, subjects will report to the ASU-NCRC Human
      Performance Lab, be oriented to the study, and provide voluntary consent. Subjects will fill
      in a medical health questionnaire to verify medical history and lifestyle habits. Subjects
      must agree to maintain normal dietary and physical activity patterns during the 12-week
      intervention, and not make formal attempts to lose body weight. All other subject inclusion
      and exclusion criteria must be maintained during the study. Subjects will be instructed on
      how to record all food intake during a 3-day period prior to the start of the study
      (Thursday, Friday, and Sunday).

      Subjects will be instructed on how to collect urine for 24-hours during the day just before
      the study starts. Urine collection guidelines:

        -  You should collect every drop of urine during each 24-hour period. It does not matter
           how much or little urine is passed each time, as long as every drop is collected.

        -  Begin the urine collection in the morning after you wake up, after you have emptied your
           bladder for the first time.

        -  Urinate (empty the bladder) for the first time and flush it down the toilet. Note the
           exact time (eg, 6:15 AM). You will begin the urine collection at this time.

        -  Collect every drop of urine during the day and night in an empty collection bottle.
           Store the bottle in the refrigerator. Be sure to collect any urine passed during bowel
           movements.

        -  Finish by collecting the first urine passed the next morning, adding it to the
           collection bottle. This should be within ten minutes before or after the time of the
           first morning void on the first day (which was flushed). In this example, you would try
           to void between 6:05 and 6:25 on the second day. If you need to urinate one hour before
           the final collection time, drink a full glass of water so that you can void again at the
           appropriate time. If you have to urinate 20 minutes before, try to hold the urine until
           the proper time.

        -  Please note the exact time of the final collection.

      B. On the first day of the study, subjects will return to the lab in a fasted state (9 or
      more hours with no food or beverage other than water) and turn in the 3-day food record and
      the 24-h urine collection sample. Height, body weight, and percent body fat (seca BIA scale)
      will be measured. Blood samples will be collected from an antecubital vein with subjects in
      the seated position by trained phlebotomists. Each blood sample will not exceed 40 ml (2.7
      tablespoons). Subjects will also record responses to a 4-week retrospective symptom log.
      Subjects will be given flavonoid or placebo supplements for the first 4-week period, and
      ingest the first two supplements in the lab under supervision.

      12-WEEK INTERVENTION: Subjects (N=110) will be randomized to the flavonoid supplement or
      placebo supplement groups for 12 weeks (thus two independent groups run in parallel with 55
      subjects). Supplements will be administered in a double-blinded manner, with the code held by
      Reoxcyn Discoveries Group until the end of the study. The goal is for N=100 subjects to
      complete all phases of the study. Subjects will ingest two supplement supplements each day of
      the study, one before breakfast, and the second one before lunch.

      Subjects will report to the Human Performance Lab at the 4- and 12-week time points in an
      overnight-fasted state and repeat all baseline measurements (including the 3-day food record
      and 24-h urine collection). The 4-week retrospective symptom logs will be filled in at
      pre-study, 4, 8, and 12 weeks (with the 8-week log administered via email). Subjects will be
      given an 8-weeks supply of the supplement after completing the 4-week lab session.

      SUPPLEMENT INFORMATION:

      The flavonoid-rich supplement contains a mixture of flavonoids from green tea and bilberry
      extracts, and quercetin. The supplement also contains food components that boost flavonoid
      benefits in the body including fish oil, caffeine, and vitamin C.

      The daily dose will be 4 flavonoid tablets (two before breakfast, two before lunch).

      Here is a detailed summary of the ingredients of the flavonoid-rich supplement (4 tablets per
      day):

      Supplement Facts Serving size: 4 Tablets Servings per container: 30 Amount per Serving %
      Daily Value Calories 50 Total Carbohydrate 12 g 4% Sugars 10 g Vitamin C (as Ascorbyl
      Palmitate) 100 mg 167% Wild Bilberry Fruit Extract (std. min. 25% Total Anthocyanins) 156 mg
      ** Green Tea Leaf Extract 180 mg ** Quercetin 100 mg ** Natural Caffeine (from Coffea arabica
      Bean) 100 mg ** NovoOmega® Omega-3 F30 Powder (Std. 30% Omega-3 Fatty Acids (Eicosapentaenoic
      Acid and Docosahexaenoic Acid)) 200 mg ** * Percent Daily Values are based on a 2,000 calorie
      diet

      ** Daily Value not Established Other Ingredients: Sugar, Natural & Artificial Flavor,
      Dextrose, Cellulose Gum, Sucralose, Bamboo Whole Plant Extract, Guar Gum, Xanthan Gum, Citric
      Acid, Malic Acid, L-Tartaric Acid Contains Fish.

      In general, the flavonoid-rich chewable tablets (4 per day) will provide the equivalent
      quantity of flavonoids as found in 10 apples, one cup of green tea, and one-fourth cup of
      bilberries. Consuming 4 tablets per day will add approximately 50% more of the beneficial
      polyphenols typically consumed by adults.
    

Intervention name(s): Flavonoid; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Flavonoid rich supplement; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: polyphenols; metabolomics; oxidative stress