Bioavailability and Pharmacokinetic Parameters of Watermelon (Rind, Flesh and Seeds) Polyphenols (WM)

Bioavailability and Pharmacokinetic Parameters of Watermelon (Rind, Flesh and Seeds) Polyphenols in Human Plasma: A Pilot Study to Investigate Relationship to Endothelial Function.

The primary objectives of the study are outlined below:

1. To investigate the relative bioavailability and absorption/kinetic profile of polyphenols after consumption of watermelon rind, flesh and seeds, respectively in an acute pilot study.
2. To study the effects of watermelon intake on endothelial function using the FMD technique and to understand the relationship between plasma metabolites, including L-citrulline and arginine, and FMD responses.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Dietary supplement: Watermelon Rind; Dietary supplement: Watermelon Flesh; Dietary supplement: Watermelon Seeds; Dietary supplement: Placebo

Detailed Description

The proposed trial will be a randomized, 4 arm, placebo controlled, within-subject crossover, study design. It is a pilot trial to establish methods and collect the preliminary data (N=6). Subjects meeting eligibility criteria (see eligibility criteria) will participate in 4 study visits where they will receive one serving (equivalent to 100 kcal) of 1 of 4 treatments: watermelon rind, watermelon flesh, watermelon seeds or placebo.

Qualified subjects from the screening visit will be randomized into the study and provided with a standard breakfast consisting of a high carbohydrate and moderate fat western-type meal 3 hours after the treatment. Each subject will be asked to come for one screening visit, a pre-study visit, and four dinner pick-ups on the day before each of the four test visits. The study day visit will last for approximately 9 h with a follow up visit the next day (24 h) for blood collection to allow for the characterization of target watermelon polyphenols and metabolites in plasma. Subjects will be instructed not to alter their usual diet or fluid intake during the study periods. Seven days prior to each study day visit, subjects will be advised not to consume fruits and vegetables rich in polyphenols and carotenoids or other high phytochemical foods (watermelon and products, arugula, spinach, tea, berries, grapes, carrots, tomatoes, sweet potatoes etc.).

Each study visit will involve with blood samples collection at time points 0 (fasting), 0.5, 1, 2, 3, 4, 5, 6, 7, 8 h and 24 hour (h). An assigned test treatment will be provided immediately after the 0 h blood collection, a breakfast meal will be provided immediately after the 2 h blood collection, and lunch after 6 h blood collection. FMD will be measured at 0 (fasting), 1, 3, 5, and 7h.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Clinical Nutrition Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Men or women, 20-45 years of age with body mass index (BMI) in range from 27.5-32 kg/m2

  • Nonsmokers (Past smokers can be allowed if they have abstinence for minimum of 2 years)
  • No clinical evidence of cardiovascular, metabolic, respiratory, renal, gastrointestinal or hepatic disease
  • Not taking any medications that would interfere with outcomes of the study, i.e. lipid lowering medications, anti-inflammatory drugs, dietary supplements especially arginine and L-citrulline, etc.
  • Able to provide informed consent
  • Able to comply and perform the procedures requested by the protocol (including dietary restrictions, consumption of study treatments, records of food diary and questionnaire, and study visit schedule)

Exclusion Criteria:

• • Men and women who smoke

  • Men and women with known or suspected intolerance, allergies or hypersensitivity to study foods or treatments
  • Men and women who consume > 2 servings of watermelons per day
  • Men and women known to have/diagnosed with diabetes mellitus
  • Men and women who have fasting blood glucose concentrations > 125 mg/dL
  • Men and women who have uncontrolled blood pressure >140 mmHg (systolic)/90 mmHg (diastolic)
  • Men and women with documented vascular disease, e.g., heart failure, myocardial infarction, stroke, angina, related surgeries, etc. that, in the opinion of the investigator, could interfere with the interpretation of the study results
  • Men and women with cancer other than non-melanoma skin cancer in previous 5 years
  • Men and women diagnosed with chronic constipation, diarrhea or other chronic gastrointestinal complaint (e.g. irritable bowel syndrome)
  • Women who are known to be pregnant or who are intending to become pregnant over the course of the study
  • Women who are lactating
  • Taking medication or dietary supplements that may interfere with the outcomes of the study; e.g., antioxidant supplement, anti-inflammation, lipid lowering medication, blood pressure lowering medication, etc... Subjects may choose to go off dietary supplements (requires 30 days washout); e.g., fish oil, probiotics, etc...
  • Men and women who have donated blood within 3 months of the Screening Visit and blood donors/participants for whom participation in this study will result in having donated more than 1500 milliliters of blood in the previous 12 months.
  • Men and women who are vegans or vegetarian
  • History of an eating disorder (e.g., anorexia nervosa, bulimia nervosa, or binge eating) diagnosed by a health professional
  • Substance (alcohol or drug) abuse within the last 2 years
  • Excessive coffee and tea consumers (> 5 cups/d)
  • Men and women who do excessive exercise regularly or an athlete
  • Unstable weight: gained or lost weight +/- 5 kg (11 lbs) in previous 2 months
  • Women who are taking unstable dose of hormonal contraceptives and/or stable dose for less than 6 months
  • Unusual working hours i.e., working overnight (e.g. 3rd shift)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active1; watermelon rind	Dietary supplement: Watermelon Rind; watermelon rind
ACTIVE_COMPARATOR: Active2; watermelon flesh	Dietary supplement: Watermelon Flesh; watermelon flesh
ACTIVE_COMPARATOR: Active3; watermelon seeds	Dietary supplement: Watermelon Seeds; watermelon seeds
PLACEBO_COMPARATOR: Control Comparator; placebo	Dietary supplement: Placebo; Control Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative characterization of watermelon polyphenolic compounds in plasma over 24-hour in humans	This will be conducted by using ultra-high performance liquid chromatography iFunnel quadrupole time of flight mass spectrometer (UHPLC-QTOF-MS) and triple quadrupole mass spectrometer (UHPLC-QQQ-MS).	24-hour Postprandial period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes in endothelial function using ultrasound technique after consumption of each treatment	Flow Mediated Vasodilation imaging of the brachial artery to assess endothelial-dependent relaxation	24-hour Postprandial period
the relationship between plasma metabolites and FMD responses after consumption of treatments	Correlation between plasma metabolites and FMD Change	24-hour Postprandial period

Collaborators and Investigators

• Sponsor: Clinical Nutrition Research Center, Illinois Institute of Technology

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 15, 2018
• Primary Completion (ACTUAL): April 1, 2019
• Study Completion (ACTUAL): April 2, 2019

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (ACTUAL): December 8, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Flow Mediated Vasodilation; Watermelon; Watermelon phytochemicals bioavailability
• Other Study ID Numbers: IRB2017-078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No