Clinical trial NCT06025357: Effects of L-citrulline Supplementation on Vascular Function in Metabolic Syndrome
Official title: Effects of L-Citrulline Supplementation on Vascular Function During Fasted and Acute Hyperglycemia in Middle-aged and Older Women With Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Menopause
Keywords: Endothelial function
Aortic Hemodynamics
Blood pressure
Obesity
Hypertension
Lead sponsor: Texas Tech University
Sponsor class: OTHER
First posted: 2023-09-06
Enrollment: 24
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment Double (Participant, Investigator) Randomized, double-blind, placebo-controlled, parallel study design
Primary purpose: BASIC_SCIENCE

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.

Detailed description: Using a double-blind, randomized, placebo-controlled, and parallel design, middle-aged and older women with metabolic syndrome will be randomized into receiving either CIT supplementation (10g/day) or placebo (Microcrystalline Cellulose) for 4 weeks.

The first visit will be approximately 1hr and 30 minutes. The 2nd and 3rd visits will each be approximately 2hrs and 30 minutes, separated by 4 weeks in between each visit. During visits 2 and 3, vascular measurements will be assessed in the fasted state and 30, 60, and 90 minutes after acute glucose ingestion (75g).

Eligibility criteria: Inclusion Criteria:

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

The following are also inclusion criteria's:

* 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.

Exclusion Criteria:

* \< 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

Primary outcomes:
measure: Macrovascular Endothelial function in the fasted condition
timeFrame: 4 weeks
measure: Microvascular endothelial function in the fasted condition
timeFrame: 4 weeks
measure: Microvascular digital endothelial function in the fasted condition
timeFrame: 4 weeks
measure: Macrovascular Endothelial function during acute hyperglycemia
timeFrame: 4 weeks
measure: Microvascular forearm endothelial function during acute hyperglycemia
timeFrame: 4 weeks
measure: Central and peripheral arterial stiffness in the fasted condition
timeFrame: 4 weeks
measure: Central arterial stiffness during acute hyperglycemia
timeFrame: 4 weeks
measure: Blood pressure in the fasted condition
timeFrame: 4 weeks
measure: Blood pressure during acute hyperglycemia
timeFrame: 4 weeks
measure: Total peripheral resistance in the fasted condition.
timeFrame: 4 weeks
measure: Total peripheral resistance during acute hyperglycemia
timeFrame: 4 weeks
measure: Stroke volume in the fasted condition
timeFrame: 4 weeks
measure: Stroke volume during acute hyperglycemia
timeFrame: 4 weeks
measure: 24-hour ambulatory blood pressure monitoring
timeFrame: 4 weeks
Secondary outcomes:
measure: Serum glucose and insulin levels.
timeFrame: 4 weeks
measure: Serum arginine levels
timeFrame: 4 weeks
measure: Serum arginase levels
timeFrame: 4 weeks
measure: Serum Nitric Oxide levels
timeFrame: 4 weeks
measure: Serum Endothelin-1 levels
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Lubbock
country: United States
facility: TTU Kinesiology and Sport Management Building
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. 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: 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: 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: 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.
citation: 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.