Watermelon Supplementation and Arterial Stiffness

Effects of Oral L-citrulline/L-arginine in Watermelon on Central Blood Pressure and Arterial Stiffness in Individuals With Obesity-related High Blood Pressure

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Dietary supplement: Watermelon Extract

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tallahassee, Florida, United States, 32306
      • Cardiovascular Physiology Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Thirty men and women 45-70 years of age
• BP between 120-159/80-99 mmHg
• Waist circumference >102 cm in men and > 80 cm in women

Exclusion Criteria:

• BP >160/100 mmHg
• Asthma
• Glaucoma
• Herpes simplex
• Uncontrolled diabetes
• Neurological disease
• Cardiovascular disease
• Inflammatory disease
• Kidney disease
• Hormone replacement therapy (HRT)
• Amino acid/vitamin supplementation\
• Corticosteroids or non-steroidal anti-inflammatory drugs
• Any drug known to affect BP or heart rate
• Glycemic control drugs
• Lipids reducing drugs
• Participants should not consume > 12 alcoholic drink/week
• Smokers
• Regular Exercisers (= 1.5 hour/week).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Maltodextrin; 6g/day of placebo (maltodextrin)	Dietary supplement: Watermelon Extract; 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 Names: Watermelon extract from Milne fruit Products Inc
Experimental: Watermelon; (6g per day)containing L-citrulline/L-arginine (4/2 g)	Dietary supplement: Watermelon Extract; 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 Names: Watermelon extract from Milne fruit Products Inc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	By measuring brachial and central (aortic and carotid) BP at rest and during physiological stress (head-up tilt test and cold pressor test)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial Stiffness	Using pulse wave velocity of the aorta and legs.	12 weeks
Endothelial function	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).	12 weeks
Autonomic control of BP	By measuring BP variability and BRS at rest and during physiological stress	12 weeks
Autonomic control of heart rate	By measuring heart rate variability at rest and during physiological stress	12 weeks

Collaborators and Investigators

• Sponsor: Florida State University
• Investigators: Principal Investigator: Arturo Figueroa, MD, PhD, The Florida State University

Publications and helpful links

General Publications

• Figueroa A, Wong A, Kalfon R. Effects of watermelon supplementation on aortic hemodynamic responses to the cold pressor test in obese hypertensive adults. Am J Hypertens. 2014 Jul;27(7):899-906. doi: 10.1093/ajh/hpt295. Epub 2014 Feb 26.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: August 17, 2010
• First Submitted That Met QC Criteria: August 18, 2010
• First Posted (Estimate): August 19, 2010

Study Record Updates

• Last Update Posted (Estimate): March 20, 2012
• Last Update Submitted That Met QC Criteria: March 17, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Obesity; Arterial Stiffness; Aortic Blood Pressure; Wave Reflection; Watermelon Supplementation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: RF02032