Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders

NCT ID: NCT03626168

Last Updated: 2022-05-17

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-16

Study Completion Date

2018-05-12

Brief Summary

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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

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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.

Conditions

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Arterial Stiffness Inflammation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

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 Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
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 Groups

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Consumption of 100% watermelon juice

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

Group Type ACTIVE_COMPARATOR

100% watermelon juice

Intervention Type DIETARY_SUPPLEMENT

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

Consumption of a placebo beverage

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

Group Type PLACEBO_COMPARATOR

Placebo beverage

Intervention Type OTHER

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

Interventions

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100% watermelon juice

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

Intervention Type DIETARY_SUPPLEMENT

Placebo beverage

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

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

55 Years

Maximum Eligible Age

69 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Alabama, Tuscaloosa

OTHER

Sponsor Role lead

Responsible Party

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Amy Ellis

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Amy C Ellis, PhD, RD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Kristi Crowe-White, PhD, RD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

References

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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. doi: 10.1080/21551197.2016.1250693.

Reference Type BACKGROUND
PMID: 27897608 (View on PubMed)

Ellis AC, Mehta T, Nagabooshanam VA, Dudenbostel T, Locher JL, Crowe-White KM. Daily 100% watermelon juice consumption and vascular function among postmenopausal women: A randomized controlled trial. Nutr Metab Cardiovasc Dis. 2021 Sep 22;31(10):2959-2968. doi: 10.1016/j.numecd.2021.06.022. Epub 2021 Jul 7.

Reference Type DERIVED
PMID: 34344546 (View on PubMed)

Crowe-White KM, Voruganti VS, Talevi V, Dudenbostel T, Nagabooshanam VA, Locher JL, Ellis AC. Variation of Serum Lycopene in Response to 100% Watermelon Juice: An Exploratory Analysis of Genetic Variants in a Randomized Controlled Crossover Study. Curr Dev Nutr. 2020 Jun 17;4(7):nzaa102. doi: 10.1093/cdn/nzaa102. eCollection 2020 Jul.

Reference Type DERIVED
PMID: 32695957 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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16MCPRP27260233

Identifier Type: -

Identifier Source: org_study_id

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