Skip to content

Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03626168
Acronym
MOXIE
Enrollment
21
Registered
2018-08-10
Start date
2016-02-16
Completion date
2018-05-12
Last updated
2022-05-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Arterial Stiffness, Inflammation

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.

Interventions

DIETARY_SUPPLEMENT100% watermelon juice

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

OTHERPlacebo beverage

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

Sponsors

University of Alabama, Tuscaloosa
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, 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.

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.

Eligibility

Sex/Gender
FEMALE
Age
55 Years to 69 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Change From Baseline in Serum Levels of Lycopene at 4 WeeksBaseline and 4 WeeksLycopene determined by ultra high performance liquid chromatography with photodiode array detector (UPLC-PDA).
Change in Vascular Endothelial Function at 4 WeeksBaseline and 4 weeksDetermined by brachial artery flow-mediated dilation (FMD). FMD uses ultrasound technology to quantify changes in brachial artery diameter in response to hyperemia. A blood pressure cuff was placed distal to the brachial artery of the right arm with the participant supine and rested. Pre-inflation diameter was recorded for one minute, and the cuff was inflated to 50 mmHg above resting SBP for five minutes. Then, images were recorded for 120 seconds after cuff deflation. Peak diameter was determined as an average of the five highest measurements over five seconds post-deflation. FMD was expressed as the percentage increase in peak diameter.
Change in Arterial Stiffness at 4 WeeksBaseline and 4 weeksDetermined by pulse wave velocity (PWV). A cuff-based system was used to measure brachial oscillometric pressure waveforms and generate central pressure curves by propriety algorithms. PWV was quantified as the rate at which a pulse wave moves down a vessel.

Participant flow

Participants by arm

ArmCount
100% Watermelon Juice First, Then Placebo Beverage
Consumption of two 12-ounce doses of pasteurized 100% watermelon juice for a four-week period 2-week washout period Consumption of two 12-ounce doses of placebo beverage for a four-week period
9
Placebo Beverage First, Then 100% Watermelon Juice
Consumption of two 12-ounce doses of placebo beverage for a four-week period 2-week washout period Consumption of two 12-ounce doses of 100% watermelon juice for a four-week period
11
Total20

Withdrawals & dropouts

PeriodReasonFG000FG001
First Intervention (4 Weeks)Began a medication that precluded participation01
First Intervention (4 Weeks)Withdrawal by Subject10
Second Intervention (4 Weeks)Withdrawal by Subject02

Baseline characteristics

CharacteristicPlacebo Beverage First, Then 100% Watermelon Juice100% Watermelon Juice First, Then Placebo BeverageTotal
Age, Continuous58.91 years
STANDARD_DEVIATION 2.91
61.78 years
STANDARD_DEVIATION 4.99
60.20 years
STANDARD_DEVIATION 4.14
Body mass index (BMI)27.12 kg/m^2
STANDARD_DEVIATION 2.51
22.61 kg/m^2
STANDARD_DEVIATION 3.21
25.08 kg/m^2
STANDARD_DEVIATION 3.6
Flow-mediated dilation (FMD)7.93 percentage of change in diameter
STANDARD_DEVIATION 6.04
10.17 percentage of change in diameter
STANDARD_DEVIATION 7.44
8.94 percentage of change in diameter
STANDARD_DEVIATION 6.62
Oxidized LDL75.61 uM/dl
STANDARD_DEVIATION 9.93
75.10 uM/dl
STANDARD_DEVIATION 12.1
75.41 uM/dl
STANDARD_DEVIATION 10.48
Oxygen radical absorbance capacity (ORAC)827.67 uM Trolox Equivalents
STANDARD_DEVIATION 231.07
642.05 uM Trolox Equivalents
STANDARD_DEVIATION 196.4
749.51 uM Trolox Equivalents
STANDARD_DEVIATION 231.36
Pulse wave velocity (PWV)8.20 meters per second
STANDARD_DEVIATION 0.69
8.40 meters per second
STANDARD_DEVIATION 0.75
8.29 meters per second
STANDARD_DEVIATION 0.71
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
11 Participants9 Participants20 Participants
Region of Enrollment
United States
11 participants9 participants20 participants
Serum arginine54.64 uM
STANDARD_DEVIATION 16.1
65.51 uM
STANDARD_DEVIATION 24.54
58.87 uM
STANDARD_DEVIATION 19.87
Serum citrulline24.23 uM
STANDARD_DEVIATION 6.16
30.43 uM
STANDARD_DEVIATION 6.82
26.64 uM
STANDARD_DEVIATION 6.96
Serum lycopene1.26 uM
STANDARD_DEVIATION 0.87
1.55 uM
STANDARD_DEVIATION 0.7
1.37 uM
STANDARD_DEVIATION 0.8
Sex: Female, Male
Female
11 Participants9 Participants20 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants
TNF-alpha2.52 pg/ml
STANDARD_DEVIATION 0.56
2.32 pg/ml
STANDARD_DEVIATION 0.37
2.44 pg/ml
STANDARD_DEVIATION 0.5
Weight69.96 kg
STANDARD_DEVIATION 5.75
59.69 kg
STANDARD_DEVIATION 10.07
65.34 kg
STANDARD_DEVIATION 9.36

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 170 / 17
other
Total, other adverse events
0 / 170 / 17
serious
Total, serious adverse events
0 / 170 / 17

Outcome results

Primary

Change From Baseline in Serum Levels of Lycopene at 4 Weeks

Lycopene determined by ultra high performance liquid chromatography with photodiode array detector (UPLC-PDA).

Time frame: Baseline and 4 Weeks

Population: Serum lycopene was unavailable for one participant due to an insufficient blood sample. With the crossover design, participants completed both arms of the study with a two-week washout period in between.

ArmMeasureValue (MEAN)Dispersion
Consumption of 100% Watermelon JuiceChange From Baseline in Serum Levels of Lycopene at 4 Weeks7.30 uMStandard Deviation 7.55
Consumption of a Placebo BeverageChange From Baseline in Serum Levels of Lycopene at 4 Weeks3.09 uMStandard Deviation 4.92
Primary

Change in Arterial Stiffness at 4 Weeks

Determined by pulse wave velocity (PWV). A cuff-based system was used to measure brachial oscillometric pressure waveforms and generate central pressure curves by propriety algorithms. PWV was quantified as the rate at which a pulse wave moves down a vessel.

Time frame: Baseline and 4 weeks

Population: With the crossover design, participants completed both arms of the study with a two-week washout period in between.

ArmMeasureValue (MEAN)Dispersion
Consumption of 100% Watermelon JuiceChange in Arterial Stiffness at 4 Weeks-0.029 meters/secondStandard Deviation 0.269
Consumption of a Placebo BeverageChange in Arterial Stiffness at 4 Weeks-0.188 meters/secondStandard Deviation 0.486
Primary

Change in Vascular Endothelial Function at 4 Weeks

Determined by brachial artery flow-mediated dilation (FMD). FMD uses ultrasound technology to quantify changes in brachial artery diameter in response to hyperemia. A blood pressure cuff was placed distal to the brachial artery of the right arm with the participant supine and rested. Pre-inflation diameter was recorded for one minute, and the cuff was inflated to 50 mmHg above resting SBP for five minutes. Then, images were recorded for 120 seconds after cuff deflation. Peak diameter was determined as an average of the five highest measurements over five seconds post-deflation. FMD was expressed as the percentage increase in peak diameter.

Time frame: Baseline and 4 weeks

Population: With the crossover design, participants completed both arms of the study with a two-week washout period in between.

ArmMeasureValue (MEAN)Dispersion
Consumption of 100% Watermelon JuiceChange in Vascular Endothelial Function at 4 Weeks2.85 percentage of change in diameterStandard Deviation 7.81
Consumption of a Placebo BeverageChange in Vascular Endothelial Function at 4 Weeks2.17 percentage of change in diameterStandard Deviation 9.25

Source: ClinicalTrials.gov · Data processed: Feb 22, 2026