Markers of Atherosclerosis in Overweight, Postmenopausal Women Following Daily Watermelon Consumption

Expression of Systemic Markers of Atherosclerosis in Free-living, Overweight, Postmenopausal Women Following Daily Watermelon Consumption for Six Weeks: A Randomized Controlled Trial

The primary purpose of this study is to determine the effectiveness of six weeks of watermelon puree supplementation, compared to control (no treatment), on blood antioxidant capacity, inflammation markers in the blood, biomarkers of metabolism in the blood, and cardiovascular disease markers in the blood, and biomarkers in the blood related to watermelon ingestion in overweight post-menopausal women. The secondary purpose is to compare body composition and body mass between the watermelon supplement group and the control group.

Study Overview

• Status: Completed
• Conditions: Overweight and Obesity; Postmenopausal
• Intervention / Treatment: Dietary supplement: Watermelon

Detailed Description

ORIENTATION AND PRE-STUDY TESTING (1-2 hours):

1. Come to the Lab in the morning in an overnight fasted state.
2. Complete orientation to the study, and provide voluntary consent to join the study.
3. Complete a medical health questionnaire to verify medical history and lifestyle habits, and provide a 3-day food record.
4. Record symptoms on a questionnaire regarding how subjects have felt for the previous four weeks using a 12-point Likert scale. Symptoms relate to digestive health, hunger, energy, infection, pain, allergies, stress, mental focus, and overall wellbeing.
5. All forms reviewed to determine eligibility to participate in this study.
6. Subject height, body weight, and percent body fat measured.
7. A blood sample taken by a trained phlebotomist; the sample not to exceed 40 mL. Blood tested for markers associated with inflammation and cardiovascular health, and nutritional compounds related to drinking watermelon puree.
8. Subjects randomized to the Control or Watermelon group. If assigned to the Watermelon group subjects provided a six-week supply of watermelon puree.
9. The morning of the study subjects consume the three bottles of watermelon puree (710 mL total, Watermelon group) each day thereafter for six weeks or maintain normal daily fluid intake (Control group).
10. Six weeks after beginning the study subjects return to the Laboratory for the final measurements. Subjects to bring all beverage bottles.

6-WEEK LAB VISIT (1-2 hours):

1. Participants come to the Lab in the morning in an overnight fasted state.
2. Subject body weight, and percent body fat are measured.
3. Subjects record symptoms on a questionnaire regarding how they have felt for the previous six weeks.
4. A final blood sample (40 mL) taken by a trained phlebotomist.

BLOOD SAMPLE ANALYSES

1. Blood borne cardiovascular disease markers: ADAM metallopeptidase with thrombospondin type 1 motif, 13 (ADAMTS13), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble P-selectin (sP-selectin), growth differentiation factor-15 (GDF-15), and soluble intercellular adhesion molecule-1 (sICAM-1) measured according to the manufacturer's specifications using the MAGPIX instrument and xPONENT analysis software (Luminex, Austin, TX).
2. Fasting blood glucose, insulin, vitamin C, and high-sensitivity C-reactive (hs-CRP) protein were measured by LabCorp (Burlington, NC).
3. Fasting plasma carotenoid concentrations measured commercially (Craft Technologies Inc., Wilson, NC).
4. Fasting plasma amino acid concentration determined by high-performance liquid chromatography.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Boone, North Carolina, United States, 28608
      • Appalachian State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female
• 50 to 75 years of age,
• have not menstruated for at least 1 year (menopause),
• have a BMI of ≥25 kg/m2,
• nonsmoker with
• no diagnosed history of chronic diseases including: coronary heart disease, stroke, cancer, type 1 or 2 diabetes mellitus, or rheumatoid arthritis;
• may not regularly consume large quantities of L-citrulline/L-arginine rich foods (red meat, tuna fish, cheese, nuts),
• may not regularly take L-citrulline/L-arginine supplements,
• may not use anti-hypertension medications (including diuretic medications),
• may not use exogenous ovarian hormones, or
• may not use medications known to influence inflammation within the two weeks of the study period (specifically non-steroidal anti-inflammatory drugs; NSAIDS).

Exclusion Criteria:

• Male,
• younger than 50 or older than 75 years of age,
• menstruated within the last year,
• have a BMI of <25 kg/m2, smoker,
• diagnosed history of chronic diseases including: coronary heart disease, stroke, cancer, type 1 or 2 diabetes mellitus, or rheumatoid arthritis;
• regularly consume large quantities of L-citrulline/L-arginine rich foods (red meat, tuna fish, cheese, nuts),
• regularly take L-citrulline/L-arginine supplements,
• use anti-hypertension medications (including diuretic medications),
• use exogenous ovarian hormones, or
• use medications known to influence inflammation within the two weeks of the study period (specifically non-steroidal anti-inflammatory drugs; NSAIDS).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control; No intervention
EXPERIMENTAL: Watermelon; Watermelon puree 710 mL per day for six weeks	Dietary supplement: Watermelon; Pureed whole (100%) watermelon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in select plasma cardiovascular disease markers	Plasma concentrations of ADAMTS13, sVCAM-1, sP-selectin, GDF-15, hs-CRP, and sICAM-1	Pre-study and study completion (6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose	Fasting blood glucose	Pre-study and study completion (6 weeks)
Blood insulin	Fasting blood insulin	Pre-study and study completion (6 weeks)
Blood carotenoids	Fasting blood carotenoids	Pre-study and study completion (6 weeks)
Blood amino acids	Fasting blood amino acids	Pre-study and study completion (6 weeks)
Body mass	Body mass (kg)	Pre-study and study completion (6 weeks)
Body mass index	Body mass index (kg/m2)	Pre-study and study completion (6 weeks)

Collaborators and Investigators

• Sponsor: Appalachian State University
• Collaborators: National Watermelon Promotion Board; https://www.watermelon.org
• Investigators: Principal Investigator: R. Andrew Shanely, Ph.D., Appalachian State University

Publications and helpful links

General Publications

• Collins JK, Wu G, Perkins-Veazie P, Spears K, Claypool PL, Baker RA, Clevidence BA. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition. 2007 Mar;23(3):261-6. doi: 10.1016/j.nut.2007.01.005.
• Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and risk of cardiovascular disease: the Framingham study. Ann Intern Med. 1976 Oct;85(4):447-52. doi: 10.7326/0003-4819-85-4-447.
• Lum T, Connolly M, Marx A, Beidler J, Hooshmand S, Kern M, Liu C, Hong MY. Effects of Fresh Watermelon Consumption on the Acute Satiety Response and Cardiometabolic Risk Factors in Overweight and Obese Adults. Nutrients. 2019 Mar 12;11(3):595. doi: 10.3390/nu11030595.
• Edwards AJ, Vinyard BT, Wiley ER, Brown ED, Collins JK, Perkins-Veazie P, Baker RA, Clevidence BA. Consumption of watermelon juice increases plasma concentrations of lycopene and beta-carotene in humans. J Nutr. 2003 Apr;133(4):1043-50. doi: 10.1093/jn/133.4.1043.
• Cook-Mills JM, Marchese ME, Abdala-Valencia H. Vascular cell adhesion molecule-1 expression and signaling during disease: regulation by reactive oxygen species and antioxidants. Antioxid Redox Signal. 2011 Sep 15;15(6):1607-38. doi: 10.1089/ars.2010.3522. Epub 2011 May 11.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2014
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (ACTUAL): July 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 11, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: cardiovascular disease; inflammation; insulin; L-arginine; glucose; L-citrulline; watermelon
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Body Weight; Overweight; Atherosclerosis
• Other Study ID Numbers: 14-0092

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