Effect of 4 Weeks of Citrulline and Glutathione Supplementation on Arterial Function

Effects of 4 Weeks Supplementation With L-Citrulline and Glutathione on Arterial Function and Cardiovascular Responses in Postmenopausal Healthy Women: A Pilot Study

Examining the effects of 4 weeks of Citrulline alone or in combination with glutathione on the arterial function of postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Menopause; Cardiovascular Risk Factor
• Intervention / Treatment: Dietary supplement: L-Citrulline; Dietary supplement: L-Citrulline; Dietary supplement: Glutathione; Dietary supplement: Placebo

Detailed Description

L-Citrulline is a non-protein amino acid and an efficient precursor of L-arginine, the substrate for endothelial nitric oxide synthesis. Glutathione is a tripeptide with antioxidant effects. Postmenopausal women will ingest 6g/d of L-Citrulline or 2g of L-Citrulline plus 200mg/d of glutathione or placebo (maltodextrin) for 4 weeks with vascular function testing prior to and after the intervention.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Lubbock, Texas, United States, 79409
      • TTU Kinesiology and Sport Management Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Generally healthy, postmenopausal women (defined as the absence of menstruation for at least 1 year).
2. Between the ages of 50-79 years.
3. Body mass index of 18.5 - 34.9 kg/m2.
4. Brachial systolic blood pressure < 150 mmHg, and diastolic blood pressure < 90 mmHg.
5. Sedentary (defined as < 120 min/week of exercise).
6. Be willing and able to comfortably abstain from any of food supplements for the period of time beginning 1 month prior to the study to the time of the termination of the study.
7. Not participating as a subject in another study for at least 2 months prior to the study and for the duration of this study.

Exclusion Criteria:

1. Current or prior use of tobacco products, e-cigarettes or other inhaled substance.
2. Use of medications and/or any supplements that may affect outcome variables (such as arginine-containing supplements, nitroglycerin, statin drugs, but not limited to those.)
3. Taking hormone replacement therapy during the 3 months before the study.
4. More than a moderate intake of alcohol (>7 drink per week).
5. Cardiovascular diseases, diabetes and other metabolic or chronic diseases.
6. Musculoskeletal disorders that will prevent exercise performance.

7. Currently taking more than one vasoactive drug for blood pressure control.

   • Subject having no more than one drug for prevention, which does not affect variables, may be included, but will be diagnosed as not having a disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-Citrulline + Glutathione; Citrulline: 2 grams/day, Glutathione: 200mg/day for 4 weeks	Dietary supplement: L-Citrulline; Four weeks of oral L-Citrulline (2 grams/day) supplementation. Supplementation will be ingested daily, half of the doses in the morning and half at night.; Dietary supplement: L-Citrulline; Four weeks of oral L-Citrulline (6 grams/day) supplementation. Supplementation will be ingested daily, half of the doses in the morning and half at night.; Dietary supplement: Glutathione; Four weeks of Glutathione (200mg/day) supplementation. Supplementation will be ingested daily, half of the doses in the morning and half at night.
Experimental: L-Citrulline; Citrulline: 6 grams/day	Dietary supplement: L-Citrulline; Four weeks of oral L-Citrulline (2 grams/day) supplementation. Supplementation will be ingested daily, half of the doses in the morning and half at night.; Dietary supplement: L-Citrulline; Four weeks of oral L-Citrulline (6 grams/day) supplementation. Supplementation will be ingested daily, half of the doses in the morning and half at night.
Placebo Comparator: Placebo; Maltodextrin: 6 grams/day	Dietary supplement: Placebo; Four weeks of oral placebo (6 grams/day maltodextrin) supplementation. Supplementation will be ingested daily, half of the doses in the morning and half at night.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in endothelial function	Endothelial function will be measured before and after the intervention using brachial artery flow mediated dilation at rest, blood flow measured in the brachial artery during handgrip exercise, and blood flow in the common femoral artery during passive leg movement. All measurements performed using doppler ultrasound.	4 weeks
Change in arterial stiffness	Arterial stiffness will be assessed through measurement of pulse-wave velocity of the carotid-femoral, carotid radial, carotid-ankle and femoral ankle arterial segments before and after the 4 week interventions.	4 weeks
Blood pressure control during the cold pressor test	Blood pressure will be measured during the cold pressor test before and after the 4 weeks.	4 weeks
L-Arginine bioavailability	Plasma levels of arginine will be measured before and after the 4 week intervention.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiovascular hemodynamics using pulse wave analysis during the cold pressor test	arterial tonometry will be measured during the cold pressor test before and after the 4 week intervention.	4 weeks
body composition	We will determine whether L-citrulline + glutathione changes body composition more than L-citrulline or placebo.	4 weeks
Muscle Strength	Leg Extension strength will be measured before and after the 4 weeks.	4 weeks
L-Citrulline levels	Plasma levels of L-Citrulline will be measured before and after the 4 weeks.	4 weeks
Glutathione peroxidase levels	Blood levels of glutathione peroxidase will be measured before and after the 4 weeks	4 weeks
Malondialdehyde	blood levels of malondialdehyde will be measured before and after the 4 weeks	4 weeks
L-Ornithine levels	plasma levels of L-ornithine will be measured before and after the 4 weeks	4 weeks

Collaborators and Investigators

• Sponsor: Texas Tech University
• Collaborators: Kyowa Hakko Bio Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): April 27, 2022
• Study Completion (Actual): April 27, 2022

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Endothelial Function; Aortic Hemodynamics; Pressure Wave Reflection
• Other Study ID Numbers: 20-0152

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No