L-Citrulline for Endothelial Function in Aging

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Oklahoma

Must not be taking: Citrulline enhancers

Disqualifiers: CNS disease, Uncontrolled seizures, Major depression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how L-Citrulline, a supplement often associated with muscle and exercise benefits, might enhance blood vessel function in the brain. The study focuses on its effects as people age. Individuals aged 21-45 or 55-90 without serious brain or psychiatric conditions may qualify for participation. Participants will take L-Citrulline daily for a week to assess its impact on brain health. As a Phase 1 trial, this research aims to understand how L-Citrulline functions in humans, providing an opportunity to be among the first to explore its potential brain health benefits.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take other Citrulline enhancers like L-Arginine or L-Citrulline Malate within 4 weeks before starting the study.

Is there any evidence suggesting that L-Citrulline is likely to be safe for humans?

Research shows that L-Citrulline is generally safe for people. Studies have found it can improve blood vessel function and lower blood pressure, particularly in older adults. One study showed that L-Citrulline enhanced blood flow and reduced blood pressure in postmenopausal women with hypertension.

Another study discovered that oral L-Citrulline increased nitric oxide levels, aiding blood flow. This suggests it might enhance blood delivery to muscles.

No major reports of serious side effects exist, indicating that L-Citrulline is well-tolerated. However, as this is a Phase 1 trial, the primary goal is to assess its safety in people. While L-Citrulline has been used in other health studies, this trial will provide more specific safety information, particularly regarding its effects on blood vessels in the brain. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for age-related endothelial dysfunction, which often involve medications like ACE inhibitors or lifestyle changes such as diet and exercise, L-Citrulline offers a unique approach. Researchers are excited about L-Citrulline because it is a naturally occurring amino acid that may boost nitric oxide production in the body, enhancing blood vessel function. This treatment is administered orally and could potentially show improvements in endothelial function in just a week, a much quicker timeline than many existing therapies.

What evidence suggests that L-Citrulline might be an effective treatment for brain vascular function?

Research has shown that L-Citrulline, the treatment under study in this trial, can improve blood flow and blood vessel health. One study increased blood flow to the legs by 11% and made blood flow more efficient by 14% during exercise in older men. Another study found that taking L-Citrulline lowered blood pressure and improved cycling performance in healthy older adults. Additionally, L-Citrulline enhanced the function of small blood vessels in people. These benefits likely result from increased levels of nitric oxide, which helps blood vessels relax and widen. ^{2 3 5 6 7}

Who Is on the Research Team?

Andriy Yabluchanskiy, MD, PhD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for adults aged 21-45 or 55-90 with good hearing and vision, who can read/write in English, and give informed consent. It's not for those with active brain diseases, recent strokes, major uncontrolled psychiatric conditions, substance abuse issues, or those on similar treatments recently.

Inclusion Criteria

I am between 21-45 or 55-90 years old.

I can see and hear well enough to take part in exams.

I understand and can agree to the study's procedures and risks.

Exclusion Criteria

I do not have active brain disorders like MS, uncontrolled seizures, or brain cancer.

Major psychiatric disease, including major depression not currently controlled on medications, alcohol or drug abuse

Any other medical condition which, in the opinion of investigator, would render the patient inappropriate or too unstable to complete the study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive L-Citrulline 50 g/day for 1 week to assess its effect on endothelial and brain vascular function

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• L-Citrulline

Trial Overview The study tests the effects of a capsule containing L-Citrulline (2500 mg) on brain blood vessel function in healthy individuals as well as those experiencing aging-related changes.

How Is the Trial Designed?

Group I: L-Citrulline Experimental Treatment 1 Intervention

L-Citrulline 50 g/day per os for 1 week

L-Citrulline is already approved in United States, European Union for the following indications:

Approved in United States as L-citrulline for:

• Nutritional supplement

Approved in European Union as L-citrulline for:

• Nutritional supplement

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5999519/

Does L-citrulline supplementation improve exercise blood flow ... L-citrulline increases femoral blood flow by 11% and vascular conductance by 14% during lower-limb exercise in older men while no changes were observed in older ...

2. aging-us.com aging-us.com/article/101984/text

Effect of chronic nitrate and citrulline supplementation on ... These results suggest that chronic NO precursor supplementation in healthy older individuals can reduce resting BP and increase cycling performance.

3. mdpi.com mdpi.com/2072-6643/17/17/2790

Citrulline Supplementation Improves Microvascular ... The main findings are that citrulline supplementation for 4 weeks improved microvascular endothelial function and forearm muscle TOI reperfusion indices ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405844025010291

Overview of mechanisms related to citrulline malate ... This narrative review focuses on the mechanisms of Citrulline Malate (CM) supplementation and various modes of HIIT on exercise performance.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8515244/

Oral administration of l-citrulline alters the vascular delivery ... Oral l-citrulline supplementation increases blood NO levels and improves vascular endothelial function in animals and humans [[19], [20], [21]].

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6073798/

l-Citrulline Supplementation: Impact on Cardiometabolic Health These data support the notion that l-citrulline may protect against the liver damage and endothelial dysfunction induced by chronic exposure to ...

7. nature.com nature.com/articles/s41598-025-16374-x

Acute effects of combined supplementation of L-arginine ... This study investigated the effects of combined L-arginine (Arg) and citrulline-malate (CM) supplementation on aerobic, anaerobic, ...