Clinical trial NCT03626168: Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders
Official title: Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders: The MOXIE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Arterial Stiffness
Inflammation
Lead sponsor: University of Alabama, Tuscaloosa
Sponsor class: OTHER
First posted: 2018-08-10
Enrollment: 21
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
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

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.

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

Primary outcomes:
measure: Change From Baseline in Serum Levels of Lycopene at 4 Weeks
timeFrame: Baseline and 4 Weeks
measure: Change in Vascular Endothelial Function at 4 Weeks
timeFrame: Baseline and 4 weeks
measure: Change in Arterial Stiffness at 4 Weeks
timeFrame: Baseline and 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Alabama at Birmingham
name: Amy C Ellis, PhD, RD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Kristi Crowe-White, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1080/21551197.2016.1250693.
citation: 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.
citation: 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.