L-Citrulline

Overview

L-citrulline is a nonessential amino acid naturally produced in the body and found in foods like watermelon. Unlike many amino acids, it is not incorporated into proteins but plays important roles in other physiological processes. It is primarily involved in the urea cycle, where it helps convert toxic ammonia into urea for excretion. Additionally, L-citrulline is a precursor to L-arginine, which is critical for producing nitric oxide (NO), a molecule that promotes blood vessel dilation and regulates blood flow. Due to these functions, L-citrulline is commonly used as a supplement to support cardiovascular health, exercise performance, and conditions related to blood flow such as erectile dysfunction and high blood pressure¹²³.

Forms and Variations

L-citrulline supplements are typically available in powder or capsule form. The most common forms include:

• L-citrulline itself, which directly provides the amino acid.
• Citrulline malate, a combination of L-citrulline and malic acid, often used to enhance exercise performance and reduce muscle fatigue.

Choosing between these forms depends on the intended use; citrulline malate is popular among athletes for its potential to improve endurance, while pure L-citrulline is often preferred for cardiovascular support. The powder form allows flexible dosing and is commonly mixed with water or beverages¹³.

Dosage and Administration

Typical dosages of L-citrulline supplements vary based on the purpose:

• For cardiovascular benefits and blood pressure support, doses around 3 to 6 grams per day are common.
• For exercise performance enhancement, citrulline malate is often taken at doses of 6 to 8 grams before workouts.

Supplements are usually taken once or twice daily, with or without food. For best absorption and effect, it is recommended to take L-citrulline consistently over days to weeks. Hydration and timing relative to exercise may also influence benefits¹⁴.

Scientific Research and Mechanism of Action

L-citrulline acts primarily by increasing plasma levels of L-arginine, which is the substrate for nitric oxide synthase enzymes that produce nitric oxide (NO). NO is a key signaling molecule that relaxes blood vessels, improving blood flow and reducing blood pressure. Studies have shown that L-citrulline supplementation can modestly improve muscle blood flow during exercise, particularly in older adults, by enhancing NO production⁴. This improved circulation may support better oxygen and nutrient delivery to muscles, potentially enhancing exercise performance and recovery.

Research also explores L-citrulline"s role in reducing arterial stiffness and improving endothelial function, which are important for cardiovascular health. However, while promising, evidence for benefits in conditions like erectile dysfunction and pulmonary hypertension remains preliminary and requires further clinical trials¹².

Benefits and Potential Uses

Key benefits of L-citrulline supplementation include:

• Improved exercise performance: By enhancing blood flow and reducing muscle fatigue, L-citrulline may increase endurance and strength during physical activity.
• Cardiovascular support: It may help lower blood pressure and improve vascular function through nitric oxide-mediated vasodilation.
• Erectile dysfunction: Some evidence suggests L-citrulline can improve symptoms by enhancing blood flow, though more research is needed.
• Ammonia detoxification: Through its role in the urea cycle, it helps remove excess ammonia, which can be beneficial in metabolic conditions.

Other potential uses under investigation include support for sickle cell disease and pulmonary hypertension, but these require more robust clinical evidence¹².

Side Effects and Risks

L-citrulline is generally well tolerated with few reported side effects. Mild gastrointestinal symptoms such as stomach discomfort, nausea, or diarrhea may occur, especially at higher doses. There are no well-documented serious adverse effects. However, individuals with low blood pressure or those taking blood pressure medications should use caution due to the vasodilatory effects of L-citrulline. Pregnant or breastfeeding women should consult healthcare providers before use¹².

Interactions and Precautions

L-citrulline may interact with medications that affect blood pressure or blood flow, such as nitrates, phosphodiesterase inhibitors (e.g., sildenafil), and antihypertensive drugs, potentially causing excessive blood pressure lowering. Caution is advised when combining these substances. People with cardiovascular conditions or those undergoing surgery should inform their healthcare provider before supplementing. Additionally, those with kidney or liver disease should seek medical advice due to altered amino acid metabolism¹².

Impact on Biomarkers

Supplementation with L-citrulline increases plasma levels of L-arginine and nitric oxide metabolites, which are markers of improved endothelial function and vasodilation. It may also reduce blood pressure readings and improve markers of vascular health such as arterial stiffness. These changes reflect enhanced cardiovascular function and better blood flow⁴.

Overdose and Toxicity

There is limited evidence of toxicity from L-citrulline supplementation at typical doses. Excessive intake may cause gastrointestinal upset. No established toxic dose exists, but doses above 10 grams per day are generally not recommended without medical supervision. Safe upper limits have not been firmly established, so adherence to recommended dosages is advised to avoid adverse effects¹.

Disclaimer

The information provided in this document is for educational purposes only and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.