L-Citrulline and Endothelial Function

University of Oklahoma20 enrolled

Overview

The effect of L-Citrulline is well studied in relation to muscle strength, exhaustion, exercise performance, and endothelial function in health and disease. This study will extend current body of knowledge and will investigate the effect of L-Citrulline on brain vascular function.

Endothelial function is associated with nitric oxide (NO) availability for vasodilation, blood pressure and blood flow regulation, and vascular health. A large body of evidence demonstrates that aging is associated with a decrease in bioavailability of NO, with more pronounced decrease in sedentary individuals. NO can be produced via the NO synthase (NOS) enzymes, which catalyze the conversion of L-Arginine - a semi-essential amino acid found in fish, nuts and legumes amongst others - to L-Citrulline and produce NO as an endproduct. While the effect of L-Citrulline is extensively studied in relation to muscle strength, exhaustion, exercise performance, as well as on endothelial function in healthy and diseased individuals (including obese and those with heart failure), the effect of L-Citrulline on brain vascular function is not well studied.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Aging

Interventions

L-Citrulline, capsuleDRUG

5g/daily dose for the duration of 1 week intervention

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age 21-45 and ≥55-90 years of age * Adequate hearing and visual acuity to participate in the examinations * Ability to read and write in English * Competence to provide informed consent Exclusion Criteria: * Active CNS disease including multiple sclerosis, uncontrolled seizures, active brain cancer * Cerebrovascular accident other than TIA within 60 days prior to Visit 0 * Major psychiatric disease, including major depression not currently controlled on medications, alcohol or drug abuse * Treatment with other Citrulline enhancers (L-Arginine, L-Citrulline Malate) within 4 weeks prior to Visit 0 * Any other medical condition which, in the opinion of investigator, would render the patient inappropriate or too unstable to complete the study protocol

Locations (1)

Andriy Yabluchanskiy

Oklahoma City, Oklahoma, United States

Outcomes

Primary Outcomes

Change in neurovascular coupling using functional near infrared spectroscopy (fNIRS)

Functional near infrared spectroscopy (fNIRS) will be performed during the cognitive n-back task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. Neurovascular coupling will be evaluated as a change in oxy- and deoxy-hemoglobin between before and after treatment. Units of measure - beta. Reported as a %change from baseline, before and after treatment.

Time frame: 1 week

Change in neurovascular coupling using the dynamic retinal vessel analysis

Flicker light-induced dilation of the retinal vessels (percentage increase over baseline diameter) will be measured in the right or left eye of each study participant using the Dynamic Vessel Analyzer (DVA, IMEDOS Systems, Jena, Germany). Units of measure mm, reported as a %change from baseline, before and after treatment.

Time frame: 1 week

Change in neuronal activity

EEG signal will be collected to generate spectral data. These data will be used for comparison of EEG activity between before and after treatment. Units of measure - power spectral density. Reported as a %change from baseline, before and after treatment.

Time frame: 1 week

Secondary Outcomes

Change in microvascular endothelial function

Changes in microvascular endothelial function will be assessed using laser speckle contrast imaging (LSCI) in the hand using the flow mediated dilation approach. The change in skin perfusion is calculated and reported as a %change from baseline, between before and after treatment. Units of measure - perfusion index (arbitrary units). Reported as a %change from baseline, before and after treatment.

Time frame: 1 week

Change in macrovascular endothelial function

Data from ClinicalTrials.gov

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