Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders
Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders
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.
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.
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