2 Weeks of Citrulline Supplementation on Arterial Function in Postmenopausal Women With Elevated Blood Pressure or Hypertension

2 Weeks of L-Citrulline Supplementation Improves Arterial Function and Systolic Blood Pressure at Rest and During Exercise in Postmenopausal Women With Elevated Blood Pressure and Hypertension

The objective of this project is to elucidate the effect of L-Citrulline (L-CIT) supplementation on vascular function at rest and during rhythmic handgrip exercise and functional sympatholysis via lower-body negative pressure in postmenopausal women with elevated blood pressure and hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension; Menopause
• Intervention / Treatment: Dietary supplement: L-Citrulline; Dietary supplement: Placebo

Detailed Description

Using a double-blind, randomized, placebo-controlled, and crossover design, overweight or obese postmenopausal women with elevated blood pressure (BP) or hypertension will receive CIT (6 grams/day) or placebo for 2 weeks, separated by a two-week washout period.

There will be a total of 5 laboratory visits. The 1st visit will take approximately 1 hour. The 2nd - 5th visits will take about 2 hours and 15 minutes. Visit 1 will be a screening visit, visits 2 and 4 will be considered baseline visits, and visits 3 and 5 will be following the participants' two weeks of supplementation. Arterial stiffness (carotid-femoral and femoral-dorsalis pedis pulse wave velocity) and endothelial function will be assessed at rest. Additionally, brachial artery blood flow, forearm muscle oxygenation, cardiovascular hemodynamics (stroke volume, cardiac output, systemic vascular resistance), and BP will be assessed at rest, during 6 minutes of rhythmic handgrip exercise at 30% of a predetermined maximal voluntary contraction, and 2 minutes of superimposed lower body negative pressure to increase sympathetic activity.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Lubbock, Texas, United States, 79409
      • Texas Tech University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Postmenopausal women (defined as the absence of menstruation for at least 1 year).
• Resting systolic blood pressure 120-150 mmHg.
• Between the ages of 50 - 70 years.
• Sedentary (< 120 minutes of exercise/week).
• Body mass index of 25 - 39.9 kg/m2.
• Fasting glucose < 126 mg/dL and HbA1c < 6.5%.

Exclusion Criteria:

• Body mass index ≥ 40 or < 25 kg/m2.
• Systolic blood pressure > 150 mmHg.
• Taking more than two antihypertensive medications.
• Cardiovascular diseases, type I/II diabetes, musculoskeletal disorders, or cancer.
• Changes in hypertensive medication in the past three months.
• Began or changed hormone replacement therapy in the past 6 months.
• Current smoker.
• Heavy drinking (> 7 alcoholic drinks/week).
• Participants on beta-blockers or other vasodilatory supplements (nitrates).
• Incorporated in a weight loss program and/or aerobic or resistance training program.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-Citrulline; L-Citrulline: 6 grams/day divided in 2 equal doses	Dietary supplement: L-Citrulline; 2 weeks of L-Citrulline supplementation (6 grams/day)
Placebo Comparator: Placebo; Microcrystalline cellulose: 8 capsules/day divided into 2 equal doses	Dietary supplement: Placebo; 2 weeks of microcrystalline cellulose supplementation (8 capsules/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Macrovascular endothelial function at rest	Endothelial function will be assessed via brachial artery flow-mediated vasodilation (ultrasonography) during reactive hyperemia at baseline and after 2 weeks of each supplementation.	2 weeks of each intervention
Microvascular endothelial function at rest	Endothelial function will be assessed via peripheral arterial tonometry (endoPAT) during reactive hyperemia at baseline and after 2 weeks of each supplementation.	2 weeks of each intervention
Microvascular endothelial function at rest	Endothelial function will be assessed using forearm muscle oxygen saturation (near-infrared spectroscopy) during reactive hyperemia before and after 2 weeks of each supplementation.	2 weeks of each intervention
Brachial artery blood flow at rest and during rhythmic handgrip exercise with and without lower-body negative pressure	Blood flow will be measured via Doppler ultrasound before and after 2 weeks of each intervention.	2 weeks of each intervention
Forearm muscle oxygenation at rest and during rhythmic handgrip exercise with and without lower-body negative pressure	Muscle oxygen saturation will be measured via near-infrared spectroscopy before and after 2 weeks of each intervention.	2 weeks of each intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beat-to-beat blood pressure at rest and during rhythmic handgrip exercise with and without lower-body negative pressure	Blood pressure will be measured via a finger cuff (finometer) before and after 2 weeks of each intervention.	2 weeks of each intervention
Aortic hemodynamics at rest and during rhythmic handgrip exercise with and without lower body negative pressure	Aortic blood pressure and pressure waves will be assessed using radial applanation tonometry before and after 2 weeks of each intervention.	2 weeks of each intervention
Stroke volume at rest and during rhythmic handgrip exercise with and without lower body negative pressure	Stroke volume will be assessed via impedance cardiography before and after 2 weeks of each intervention.	2 weeks of each intervention
Heart rate at rest and during rhythmic handgrip exercise with and without lower body negative pressure	Heart rate will be assessed via impedance cardiography before and after 2 weeks of each intervention.	2 weeks of each intervention
Systemic vascular resistance at rest and during rhythmic handgrip exercise with and without lower body negative pressure	Systemic vascular resistance will be assessed via impedance cardiography before and after 2 weeks of each intervention.	2 weeks of each intervention
Central and peripheral arterial stiffness at rest	Carotid-femoral and femoral-dorsalis pedis pulse wave velocity will be measured using arterial applanation tonometry before and after 2 weeks of each intervention.	2 weeks of each intervention
Forearm muscle strength	Maximal forearm muscle strength will be measured using a handgrip dynamometer before and after 2 weeks of each intervention.	2 weeks of each intervention
L-arginine levels	Serum levels of l-arginine will be assessed before and after 2 weeks of each intervention.	2 weeks of each intervention
Nitric oxide levels	Serum levels of nitric oxide will be assessed before and after 2 weeks of each intervention.	2 weeks of each intervention
L-citrulline levels	Serum levels of l-citrulline will be assessed before and after 2 weeks of each intervention.	2 weeks of each intervention
L-ornithine levels	Serum levels of l-ornithine will be assessed before and after 2 weeks of each intervention.	2 weeks of each intervention

Collaborators and Investigators

• Sponsor: Texas Tech University
• Investigators: Principal Investigator: Arturo Figueroa, Texas Tech University

Publications and helpful links

General Publications

• Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Acute Citrulline Blunts Aortic Systolic Pressure during Exercise and Sympathoactivation in Hypertensive Postmenopausal Women. Med Sci Sports Exerc. 2022 May 1;54(5):761-768. doi: 10.1249/MSS.0000000000002848. Epub 2022 Jan 3.
• Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women. Nutrients. 2022 Oct 20;14(20):4396. doi: 10.3390/nu14204396.
• Kang Y, Dillon KN, Martinez MA, Maharaj A, Fischer SM, Figueroa A. Combined L-Citrulline Supplementation and Slow Velocity Low-Intensity Resistance Training Improves Leg Endothelial Function, Lean Mass, and Strength in Hypertensive Postmenopausal Women. Nutrients. 2022 Dec 23;15(1):74. doi: 10.3390/nu15010074.
• Figueroa A, Maharaj A, Kang Y, Dillon KN, Martinez MA, Morita M, Nogimura D, Fischer SM. Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women. Nutrients. 2023 Mar 23;15(7):1557. doi: 10.3390/nu15071557.
• Figueroa A, Alvarez-Alvarado S, Jaime SJ, Kalfon R. l-Citrulline supplementation attenuates blood pressure, wave reflection and arterial stiffness responses to metaboreflex and cold stress in overweight men. Br J Nutr. 2016 Jul;116(2):279-85. doi: 10.1017/S0007114516001811. Epub 2016 May 10.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: August 19, 2023
• First Submitted That Met QC Criteria: August 29, 2023
• First Posted (Actual): September 6, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Endothelial function; Blood pressure; Blood flow; Functional sympatholysis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: IRB2022-1055

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No