Effects of L-citrulline Supplementation on Vascular Function in Metabolic Syndrome

NCT06025357 | Completed

• 1 other identifier: IRB2022-362
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this project is to provide evidence that L-Citrulline (CIT) supplementation can improve vascular function in the fasted and acute hyperglycemia conditions in middle-aged and older women with metabolic syndrome.

Conditions

Metabolic Syndrome; Menopause

Keywords

Endothelial function; Aortic Hemodynamics; Blood pressure; Obesity; Hypertension

Outcome Measures

Primary Outcomes (14)

• Macrovascular Endothelial function in the fasted condition

  Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.

  4 weeks

• Microvascular endothelial function in the fasted condition

  Endothelial function will be measured using forearm muscle oxygenation (near-infrared spectroscopy) will assessed during reactive hyperemia at baseline and after 4 weeks of supplementation.

  4 weeks

• Microvascular digital endothelial function in the fasted condition

  Endothelial function will be measured using peripheral (finger) arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.

  4 weeks

• Macrovascular Endothelial function during acute hyperglycemia

  Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.

  4 weeks

• Microvascular forearm endothelial function during acute hyperglycemia

  Endothelial function will be measured using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.

  4 weeks

• Central and peripheral arterial stiffness in the fasted condition

  Arterial stiffness will be measured using central (carotid-femoral) and peripheral (femoral-ankle) PWV at baseline and after 4 weeks of supplementation.

  4 weeks

• Central arterial stiffness during acute hyperglycemia

  Arterial stiffness will be measured using central (carotid-femoral) PWV at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.

  4 weeks

• Blood pressure in the fasted condition

  Brachial and aortic blood pressures will be assessed using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Fineometer). Blood pressure will be measured at baseline and after 4 weeks of supplementation.

  4 weeks

• Blood pressure during acute hyperglycemia

  Brachial and aortic blood pressures (systolic and diastolic) will be assessed using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Fineometer). Blood pressure will be measured after an oral glucose ingestion at 30, 60, and 90 minutes at baseline and after 4 weeks of supplementation.

  4 weeks

• Total peripheral resistance in the fasted condition.

  Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.

  4 weeks

• Total peripheral resistance during acute hyperglycemia

  Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.

  4 weeks

• Stroke volume in the fasted condition

  Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.

  4 weeks

• Stroke volume during acute hyperglycemia

  Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.

  4 weeks

• 24-hour ambulatory blood pressure monitoring

  An ambulatory blood pressure cuff, measuring blood pressure for 24-hours will be obtained on two separate days at baseline and after 4 weeks of supplementation.

  4 weeks

Secondary Outcomes (5)

• Serum glucose and insulin levels.

  4 weeks

• Serum arginine levels

  4 weeks

• Serum arginase levels

  4 weeks

• Serum Nitric Oxide levels

  4 weeks

• Serum Endothelin-1 levels

  4 weeks

Study Arms (2)

L-citrulline

EXPERIMENTAL

L-citrulline: 10 grams/day

Dietary Supplement: L-Citrulline supplementation

Placebo

EXPERIMENTAL

Microcrystalline Cellulose

Dietary Supplement: Placebo

Interventions

L-Citrulline supplementation DIETARY_SUPPLEMENT

4 weeks of L-Citrulline supplementation (10 grams/day).

L-citrulline

Placebo DIETARY_SUPPLEMENT

4 weeks of microcrystalline Cellulose supplementation.

Placebo

Eligibility Criteria

• Age: 45 Years - 79 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must present at least 3 of the following 5 cardiometabolic risk factors
• Waist circumference ≥88 cm
• Fasting glucose between 100-125 mg/dL or HbA1c between 5.7-6.4%.
• Blood pressure ≥130 mm Hg
• Triglyceride ≥ 150 mg/dL
• HDL \<50 mg/dL
• Women aged 45-79 years old
• Body mass index ≤ 39.9 kg/m2
• Sedentary (defined as \< 120 min/week of exercise)
• Abstain from any dietary supplements with vascular effects for one month prior to the beginning of the study and until participation in study has terminated.

You may not qualify if:

• \< 45 and \> 79 years of age
• Use of medications and/or any supplements that may affect outcome variables (such as arginine-containing supplements, nitroglycerin, statin drugs, biguanides, insulin, beta blockers, statins, verapamil)
• Systolic blood pressure ≥ 160 mmHg
• BMI \> 40 kg/m2
• Recent changes in medication (3 months)
• Current smoking any tobacco use
• Cardiovascular disease, diabetes (Type 1 or 2), and other metabolic or chronic diseases
• More than 7 alcoholic drinks/week of consumption

Sponsors & Collaborators

• Texas Tech University: lead

Study Sites (1)

TTU Kinesiology and Sport Management Building

Lubbock, Texas, 79409, United States

Location

Related Publications (5)

• 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

• 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

• 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

• McDonald JD, Mah E, Chitchumroonchokchai C, Dey P, Labyk AN, Villamena FA, Volek JS, Bruno RS. Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability. J Nutr Biochem. 2019 Jan;63:165-176. doi: 10.1016/j.jnutbio.2018.09.018. Epub 2018 Sep 25.

  PMID: 30412905 BACKGROUND

• Figueroa A, Alvarez-Alvarado S, Ormsbee MJ, Madzima TA, Campbell JC, Wong A. Impact of L-citrulline supplementation and whole-body vibration training on arterial stiffness and leg muscle function in obese postmenopausal women with high blood pressure. Exp Gerontol. 2015 Mar;63:35-40. doi: 10.1016/j.exger.2015.01.046. Epub 2015 Jan 28.

  PMID: 25636814 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Obesity; Hypertension

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Arturo Figueroa, Principal Investigator

Model Details: Parallel Assignment Double (Participant, Investigator) Randomized, double-blind, placebo-controlled, parallel study design

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: September 6, 2023
• Study Start: January 1, 2023
• Primary Completion: May 1, 2024
• Study Completion: August 1, 2024
• Last Updated: May 15, 2025

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)