Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders: The MOXIE Study

Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders



Sponsors


Source

University of Alabama, Tuscaloosa

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


Brief Summary

Watermelon is the only food with a unique combination of amino acids and antioxidants that
may reduce artery stiffness. However, only 27% of older adults meet the daily recommendation
for fruit intake. Because it tastes good and is convenient and easy to consume, watermelon
juice is an innovative and impactful intervention to help elders easily meet recommendations
for fruit servings. If effective, this intervention would be a simple, inexpensive way to
combat cardiovascular diseases (CVD). Results will advance science by providing a better
understanding whether four-week consumption of 100% watermelon juice may impact measures of
vascular health and inflammation in postmenopausal women.

Detailed Description

Purpose and Objectives:

Vascular endothelial dysfunction is an early independent predictor of cardiovascular diseases
(CVD), the leading cause of death for women ages 60 and older in the United States1. It is
well-known that age-related decreases in vascular endothelial function are partially due to
increases in oxidative stress and inflammation.In attempts to combat CVD, previous
intervention studies have investigated provision of isolated bioactive food compounds (BFC)
in supplemental form. For example, purified lycopene has been shown to decrease oxidative
stress, and our previous work supports the supplemental use of glutamine and arginine in
improving vascular endothelial function of older adults. Arginine is a precursor for the
vasodilatory molecule nitric oxide (NO), and both glutamine and arginine have been shown to
attenuate inflammation. Thus, if supplemented together, these compounds would be expected to
exert synergist mechanistic effects that improve vascular function.

Watermelon is one of the richest sources of lycopene, and it is among the greatest plant
sources of arginine and glutamine. Watermelon also provides high amounts of citrulline (a
precursor of arginine) along with the antioxidant ascorbic acid, which enhances the
antioxidant and anti-inflammatory effects of carotenoids such as lycopene in biological
samples. To date, clinical studies evaluating the potential synergy of these compounds
provided by the whole food are lacking on mechanistic and clinical outcomes of CVD. The
effects of watermelon supplementation on robust measures of vascular function, inflammation,
and oxidative stress in women ages 60 and older are unknown. This study will evaluate the
possible impact of multiple bioactive compounds in the natural food matrix of watermelon in
order to fully characterize their potential synergy and their influence on CVD risk.
Specifically, our proposed study seeks to evaluate the influence of bioactive compounds in
100% watermelon juice, a convenient serving alternative to fresh fruit, using a randomized,
double-blind placebo-controlled trial with a crossover design.

Specific Aims:

1. Mechanistic: To determine whether community-dwelling, non-obese women ages 55-69
consuming two 12-ounce servings of 100% watermelon juice per day versus placebo for four
weeks will demonstrate:

1. increases in circulating levels of serum lycopene, citrulline, and arginine using
ultra high performance liquid chromatography with photodiode array detector
(UPLC-PDA).

2. improvement in antioxidant status as assessed by the oxygen radical absorbance
capacity assay (ORAC) of whole and deproteinated serum

3. decreases in circulating biomarkers of inflammation Hypotheses: Four-week dietary
supplementation with 100% watermelon juice will result in increased antioxidant
capacity and decreased inflammation, related to increased serum lycopene,
citrulline, and arginine

2. Clinical: To determine whether community-dwelling, women ages 55-69 consuming two
12-ounce servings of 100% watermelon juice per day versus placebo for four weeks will
exhibit:

1. improved vascular endothelial function as assessed by flow-mediated dilation (FMD)
and decreased arterial stiffness as assessed by pulse wave analysis (PWA)

2. decreased low density lipoprotein (LDL) oxidation as assessed by enzyme immunoassay
Hypotheses: Four-week dietary supplementation with 100% watermelon juice will
result in improved vascular endothelial function, decreased arterial stiffness, and
decreased LDL oxidation.

Overall Status

Completed

Start Date

2016-02-16

Completion Date

2018-05-12

Primary Completion Date

2018-05-12

Phase

N/A

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Change in serum levels of lycopene, citrulline, and arginine
Measures were assessed at baseline, week 4, week 6, and week 10.
Change in antioxidant status
Measures were assessed at baseline, week 4, week 6, and week 10.
Change in vascular endothelial function
Measures were assessed at baseline, week 4, week 6, and week 10.
Change in arterial stiffness
Measures were assessed at baseline, week 4, week 6, and week 10.

Enrollment

17

Conditions


Intervention

Intervention Type

Dietary Supplement

Intervention Name


Description

Participants drank two 12-ounce servings of 100% watermelon juice per day for a four-week period.

Arm Group Label

Consumption of 100% watermelon juice


Intervention Type

Other

Intervention Name


Description

Participants drank two 12-ounce servings of a placebo beverage per day for a four-week period.

Arm Group Label

Consumption of a placebo beverage



Eligibility

Criteria

Inclusion Criteria:

- Ambulatory

- Female

- Age 55-69 years

- Body mass index 18.5 - 29.9 kg/m2 (non-obese)

Exclusion Criteria:

- Food allergy to watermelon

- History of hypotension, chronic hypertension, chronic kidney disease, diabetes,
previous cardiac events or procedures, phenylketonuria

- Smoking or other tobacco use

- Use of anticoagulant medications, cholesterol-lowering medications, blood-pressure
medications, vasodilatory dietary supplements (garlic, fish oil), or dietary
supplements containing lycopene, ascorbic acid, L-glutamine, L-arginine, or
L-citrulline

- Weight change > 10% in the previous year

Gender

Female

Minimum Age

55 Years

Maximum Age

69 Years

Healthy Volunteers

Accepts Healthy Volunteers


Overall Official

Last Name

Role

Affiliation

Amy C Ellis, PhD, RD
Principal Investigator
University of Alabama at Birmingham
Kristi Crowe-White, PhD, RD
Principal Investigator
University of Alabama at Birmingham

Verification Date

2018-08-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

University of Alabama, Tuscaloosa

Investigator Full Name

Amy Ellis

Investigator Title

Assistant Professor


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Arm Group

Arm Group Label

Consumption of 100% watermelon juice

Arm Group Type

Active Comparator

Description

Consumption of two 12-ounce doses of pasteurized 100% watermelon juice for a four-week period


Arm Group Label

Consumption of a placebo beverage

Arm Group Type

Placebo Comparator

Description

Consumption of a placebo beverage with comparable sugar content, pH, taste, texture, and color for a four-week period



Firstreceived Results Date

N/A

Reference

Citation

Ellis AC, Dudenbostel T, Locher JL, Crowe-White K. Modulating Oxidative Stress and Inflammation in Elders: The MOXIE Study. J Nutr Gerontol Geriatr. 2016 Oct-Dec;35(4):219-242.

PMID

27897608


Acronym

MOXIE

Patient Data

Sharing Ipd

No


Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Non-Randomized

Intervention Model

Crossover Assignment

Intervention Model Description

In a double-blind crossover design, women ages 55-69 years were randomized to two 12-ounce servings of 100% watermelon juice per day or an isocaloric placebo for four weeks each with a 2-week washout period in between.

Primary Purpose

Prevention

Masking

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description

In this crossover design, the participants principal investigators, and outcomes assessors were blinded as to which treatment (100% watermelon juice or placebo) was consumed at each time.


Study First Submitted

July 24, 2018

Study First Submitted Qc

August 7, 2018

Study First Posted

August 10, 2018

Last Update Submitted

August 7, 2018

Last Update Submitted Qc

August 7, 2018

Last Update Posted

August 10, 2018


ClinicalTrials.gov processed this data on August 31, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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