Citrulline Supplementation On Vascular Responsiveness and Function in Postmenopausal Women

Study Overview
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Brief Summary
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The objective of this project is to provide evidence that L-Citrulline (L-CIT) supplementation can improve vascular function at rest and in response to exercise in postmenopausal women.

Detailed Description
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L-CIT is a non-essential amino acid that is a precursor to L-arginine, the substrate used to produce an important vasodilatory molecule called nitric oxide. The purpose of this study is to identify the effects of 6 grams of L-CIT for 4 weeks on vascular function (endothelial function, blood flow, muscle oxygenation, and blood pressure) at rest and in response to different stressors (cold pressor test, isometric and dynamic exercise).

Official Title
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L-Citrulline Supplementation to Improve Vascular Function and Responsiveness at Rest and During Exercise in Postmenopausal Women

Conditions
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Menopause

Intervention / Treatment
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* Dietary Supplement: L-Citrulline
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal (absence of menstruation > 1 year) between the ages of 50 - 79 years. Sedentary ( < 120 minutes of exercise/week) Resting systolic blood pressure < 150 mmHg and diastolic blood pressure < 90 mmHg Not participating as a subject in another study for at least 2 months prior to the study and for the duration of the study Willingness to abstain from food supplements 1 month prior to the start of the study and throughout the duration of the study Exclusion Criteria: Body mass index ≥ 40 Currently taking more than one vasoactive drug for blood pressure control Cardiometabolic diseases or other chronic diseases Taking hormone replacement therapy 3 months prior to the study Current or prior use of tobacco products More than a moderate intake of alcohol Use of medications and/or supplements that may affect outcome variables Musculoskeletal disorders that will prevent exercise performance

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double (Participant, Investigator) Randomized, double-blind, placebo-controlled, parallel study design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-Citrulline<br>L-Citrulline: 6 grams/day | Dietary Supplement: L-Citrulline<br>* 4 weeks of L-Citrulline supplementation (6 grams/day)<br>|
| Placebo Comparator: Placebo<br>Crystalline Cellulose | Dietary Supplement: Placebo<br>* 4 weeks of Placebo (crystalline cellulose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular endothelial function | Endothelial function will be assessed via reactive hyperemic index using the EndoPAT device. | 4 weeks | 
| Changes in brachial and aortic blood pressure responses via automated sphygmomanometry during metaboreflex activation | Brachial and aortic blood pressures (systolic and diastolic) will be assessed using an arm cuff during isometric handgrip exercise and postexercise muscle ischemia. | 4 weeks | 
| Changes in aortic hemodynamics using pulse wave analysis during metaboreflex activation | The speed and reflection pressures, both representing aortic hemodynamic parameters, will be assessed using radial applanation tonometry and a validated transfer function (AtCor Medical) during isometric handgrip exercise and postexercise muscle ischemia. | 4 weeks | 
| Blood flow during dynamic exercise | Blood flow will be measured using ultrasound in the superficial femoral and brachial artery during dynamic exercises superimposed with the cold pressor test. | 4 weeks | 
| Muscle oxygenation during dynamic exercise | Muscle oxygenation will be measured using near infrared spectroscopy during dynamic exercises superimposed with the cold pressor test. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum nitric oxide levels | Serum levels of nitric oxide will be assessed. | 4 weeks | 
| Changes in brachial and aortic blood pressure responses via automated sphygmomanometry during dynamic plantarflexion exercise and handgrip combined with the cold pressor test | Brachial and aortic blood pressures (systolic and diastolic) will be assessed using an arm cuff during dynamic plantarflexion exercise and handgrip combined with the cold pressor test. | 4 weeks | 
| Changes in aortic hemodynamics using pulse wave analysis during dynamic plantarflexion exercise and handgrip combined with the cold pressor test | The speed and reflection pressures, both representing aortic hemodynamic parameters, will be assessed using radial applanation tonometry and a validated transfer function (AtCor Medical) during dynamic plantarflexion exercise and handgrip combined with the cold pressor test. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelial function, Blood pressure, Blood flow