Clinical trial NCT06025383: 2 Weeks of Citrulline Supplementation on Arterial Function in Postmenopausal Women With Elevated Blood Pressure or Hypertension
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Menopause
Hypertension
Keywords: Endothelial function
Blood flow
Blood pressure
Functional sympatholysis
Lead sponsor: Texas Tech University
Sponsor class: OTHER
First posted: 2023-09-06
Enrollment: 19
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Cross-Over Assignment Double (Participant, Investigator) randomized, double-blind, placebo-controlled, cross-over study design
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Macrovascular endothelial function at rest
timeFrame: 2 weeks of each intervention
measure: Microvascular endothelial function at rest
timeFrame: 2 weeks of each intervention
measure: Microvascular endothelial function at rest
timeFrame: 2 weeks of each intervention
measure: Brachial artery blood flow at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
timeFrame: 2 weeks of each intervention
measure: Forearm muscle oxygenation at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
timeFrame: 2 weeks of each intervention
Secondary outcomes:
measure: Beat-to-beat blood pressure at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
timeFrame: 2 weeks of each intervention
measure: Aortic hemodynamics at rest and during rhythmic handgrip exercise with and without lower body negative pressure
timeFrame: 2 weeks of each intervention
measure: Stroke volume at rest and during rhythmic handgrip exercise with and without lower body negative pressure
timeFrame: 2 weeks of each intervention
measure: Heart rate at rest and during rhythmic handgrip exercise with and without lower body negative pressure
timeFrame: 2 weeks of each intervention
measure: Systemic vascular resistance at rest and during rhythmic handgrip exercise with and without lower body negative pressure
timeFrame: 2 weeks of each intervention
measure: Central and peripheral arterial stiffness at rest
timeFrame: 2 weeks of each intervention
measure: Forearm muscle strength
timeFrame: 2 weeks of each intervention
measure: L-arginine levels
timeFrame: 2 weeks of each intervention
measure: Nitric oxide levels
timeFrame: 2 weeks of each intervention
measure: L-citrulline levels
timeFrame: 2 weeks of each intervention
measure: L-ornithine levels
timeFrame: 2 weeks of each intervention
Other outcomes:
Locations:
city: Lubbock
country: United States
facility: Texas Tech University
state: Texas
Study officials:
affiliation: Texas Tech University
name: Arturo Figueroa
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.