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

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.

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.

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

Endothelial function will be assessed via brachial artery flow-mediated vasodilation (ultrasonography) during reactive hyperemia at baseline and after 2 weeks of each supplementation.

Endothelial function will be assessed via peripheral arterial tonometry (endoPAT) during reactive hyperemia at baseline and after 2 weeks of each supplementation.

Endothelial function will be assessed using forearm muscle oxygen saturation (near-infrared spectroscopy) during reactive hyperemia before and after 2 weeks of each supplementation.

Brachial artery blood flow at rest and during rhythmic handgrip exercise with and without lower-body negative pressure

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.

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.

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.

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.

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.

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.

Carotid-femoral and femoral-dorsalis pedis pulse wave velocity will be measured using arterial applanation tonometry before and after 2 weeks of each intervention.

Maximal forearm muscle strength will be measured using a handgrip dynamometer before and after 2 weeks of each intervention.

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.

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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.