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

NCT06025383 | Completed

• 1 other identifier: IRB2022-1055
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Menopause; Hypertension

Keywords

Endothelial function; Blood flow; Blood pressure; Functional sympatholysis

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (11)

• Beat-to-beat blood pressure at rest and during rhythmic handgrip exercise with and without lower-body negative pressure

  2 weeks of each intervention

• Aortic hemodynamics at rest and during rhythmic handgrip exercise with and without lower body negative pressure

  2 weeks of each intervention

• Stroke volume at rest and during rhythmic handgrip exercise with and without lower body negative pressure

  2 weeks of each intervention

• Heart rate at rest and during rhythmic handgrip exercise with and without lower body negative pressure

  2 weeks of each intervention

• Systemic vascular resistance at rest and during rhythmic handgrip exercise with and without lower body negative pressure

  2 weeks of each intervention

Study Arms (2)

L-Citrulline

EXPERIMENTAL

L-Citrulline: 6 grams/day divided in 2 equal doses

Dietary Supplement: L-Citrulline

Placebo

PLACEBO COMPARATOR

Microcrystalline cellulose: 8 capsules/day divided into 2 equal doses

Dietary Supplement: Placebo

Interventions

L-Citrulline DIETARY_SUPPLEMENT

2 weeks of L-Citrulline supplementation (6 grams/day)

L-Citrulline

Placebo DIETARY_SUPPLEMENT

2 weeks of microcrystalline cellulose supplementation (8 capsules/day)

Placebo

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Texas Tech University: lead

Study Sites (1)

Texas Tech University

Lubbock, Texas, 79409, United States

Location

Related Publications (5)

• 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.

  PMID: 34974502 BACKGROUND

• 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.

  PMID: 36297080 BACKGROUND

• 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.

  PMID: 36615732 BACKGROUND

• 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.

  PMID: 37049398 BACKGROUND

• 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.

  PMID: 27160957 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Arturo Figueroa

  Texas Tech University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Arturo Figueroa, Principal Investigator

Model Details: Cross-Over Assignment Double (Participant, Investigator) randomized, double-blind, placebo-controlled, cross-over study design

Study Record Dates

• First Submitted: August 19, 2023
• First Posted: September 6, 2023
• Study Start: July 20, 2023
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: May 15, 2025

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)