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

Trial Summary

What is the purpose of this trial?

This trial is studying the effects of L-Citrulline on brain blood vessel function. L-Citrulline is a supplement that can help improve blood flow by increasing nitric oxide levels in the body. The study focuses on older and less active people who often have lower nitric oxide levels. L-Citrulline has been shown to increase nitric oxide production, which can improve blood flow and has been studied for its effects on exercise performance and cardiovascular health.

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.

What evidence supports the effectiveness of the treatment L-Citrulline for improving endothelial function in aging?

Research shows that L-Citrulline can improve blood vessel function and increase nitric oxide levels, which are important for heart health. It has been found to help lower blood pressure and protect against age-related blood vessel issues, making it potentially beneficial for older adults. ^{1 2 3 4 5}

Is L-Citrulline safe for human use?

L-Citrulline is generally considered safe for human use, as it has been safely used in individuals with certain metabolic disorders and shows promise in improving cardiovascular health. It is also used in various studies without significant safety concerns, even in critically ill patients. ^{3 4 5 6 7}

How does the drug L-Citrulline differ from other treatments for improving endothelial function in aging?

L-Citrulline is unique because it effectively increases nitric oxide (NO) levels, which is crucial for improving endothelial function, by serving as a precursor to L-arginine without being extensively broken down in the gut or liver. This makes it more effective than L-arginine supplements, which are less efficient at boosting NO due to their breakdown before reaching the bloodstream. ^{1 3 4 5 8}

Research Team

Andriy Yabluchanskiy, MD, PhD

Principal Investigator

University of Oklahoma

Eligibility Criteria

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.

Ability to read and write in English

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

L-Citrulline Supports Vascular and Muscular Benefits of Exercise Training in Older Adults. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Aging-associated endothelial dysfunction in humans is reversed by L-arginine. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727). [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Administration of L-arginine plus L-citrulline or L-citrulline alone successfully retarded endothelial senescence. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

l-Citrulline Supplementation: Impact on Cardiometabolic Health. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Citrulline in health and disease. Review on human studies. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Combined L-Citrulline Supplementation and Slow Velocity Low-Intensity Resistance Training Improves Leg Endothelial Function, Lean Mass, and Strength in Hypertensive Postmenopausal Women. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. [2022]