Watermelon Supplementation and Arterial Stiffness
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Increased abdominal obesity (waist circumference) and systolic blood pressure (BP) are main
      risk factors for the metabolic syndrome. Approximately 60% of adults in the United States are
      prehypertensive or hypertensive. Hypertension has been associated with abnormal endothelial
      and autonomic function, the two main mechanisms of BP regulation. Endothelial dysfunction, as
      a result of reduced NO (a vasodilator), and increased sympathetic nervous system activity
      contribute to arterial stiffness by enhancing the vasomotor tone. Because BP variations are
      sensed by baroreceptors in the wall of large arteries, increased stiffness of arteries may
      attenuate the control of BP by the autonomic nervous system leading to hypertension. High
      production of proinflammatory cytokines and low adiponectin (vascular protective molecule),
      are considered the underlying mechanisms leading to endothelial dysfunction and arterial
      stiffness. The recommended intervention for controlling BP in overweight/obese individuals
      with pre- and stage 1- hypertension is lifestyle modifications and not drug therapy. Among
      the dietary regimens that are reported to reduce BP is L-arginine, the substrate for
      endothelial NO production. Recently, oral L-citrulline has been shown to be more effective
      than L-arginine in improving circulating NO levels because is not affected by enzymatic
      degradation. Watermelon, the leading US melon crop, is one of the few natural foods rich in
      L-citrulline which is efficiently transformed to arginine in humans. The investigators
      long-term goal is to provide feasible and effective dietary ways to reduce cardiovascular
      risk factors in individuals with high abdominal fat and BP. The overall objective of this
      study is to bring forth evidence that watermelon supplementation will reduce BP and
      cardiovascular risk factors such as arterial stiffness, autonomic dysfunction and endothelial
      dysfunction. The investigators postulate that watermelon supplementation will reduce BP and
      arterial stiffness by enhancing endothelial function and reducing vascular inflammation. The
      findings of this study will provide a foundation for disseminating feasible, safe approaches
      for preventing and combating obesity-related hypertension at its early stage which does not
      require drug therapy.
    

Detailed description: 
      The purpose of the study is to examine the effect of 12 weeks of L-citrulline/L-arginine in
      the form of watermelon supplementation on arterial function and autonomic neural control of
      the heart rate and blood pressure in older overweight/obese men and women with pre- and stage
      1- hypertension. The specific aims of the study are:

        1. To investigate the extent to which daily consumption of watermelon supplementation
           containing L-citrulline/L-arginine (4/2 g) will reduce BP and arterial stiffness. This
           aim will examine the working hypothesis that watermelon supplementation will reduce BP
           and improve arterial function. This aim will be tested by measuring brachial and central
           (aortic and carotid) BP at rest and during physiological stress (head-up tilt test and
           cold pressor test), and by evaluating arterial stiffness using pulse wave velocity of
           the aorta and legs as primary variables.

        2. To determine the effect of watermelon supplementation on endothelial function. There is
           evidence that watermelon improves endothelial function in rats. Hence, we postulate that
           watermelon in part exerts its vascular protective effects by modulating indices of
           endothelial function. This aim will be tested by measuring flow-mediated dilation using
           vascular ultrasound and circulating levels of vasodilators, vasoconstrictors, and
           markers of vascular inflammation (adiponectin, leptin, endothelin-1, angiotensin II,
           prostaglandin F2α, sVCAM-1, sICAM-1, and 8-isoprostane).

        3. To determine whether watermelon supplementation will improve the autonomic control of BP
           and heart rate in individuals with high abdominal obesity and BP. There is evidence that
           food high in L-arginine improves baroreflex sensitivity (BRS) in individuals with
           pre-hypertension. This aim will examine the working hypothesis that watermelon will
           improve cardiovascular autonomic control of BP by measuring heart rate variability, BP
           variability and BRS at rest and during physiological stress as secondary variables.
    

Intervention name(s): Watermelon Extract
Intervention type(s): Dietary Supplement
Intervention description(s): 6 weeks of watermelon extract taken in two doses of 3g each per day (6g per day)containing L-citrulline/L-arginine (4/2 g)
Other intervention name(s): Watermelon extract from Milne fruit Products Inc
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Arterial Stiffness; Wave Reflection; Watermelon Supplementation; Aortic Blood Pressure; Obesity