Bioactive Compounds in Watermelon Modulating Oxidative Stress and Inflammation in Elders
Condition: Arterial Stiffness; Inflammation
MeSH terms: Inflammation
Study type: Interventional

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.
    

Intervention name(s): 100% watermelon juice; Placebo beverage
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Participants drank two 12-ounce servings of 100% watermelon juice per day for a four-week period.; Participants drank two 12-ounce servings of a placebo beverage per day for a four-week period.
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.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention