L-Citrulline & Citrulline Malate
L-Citrulline is a non-essential amino acid, meaning the body can produce it on its own. First discovered in watermelon, it plays two primary roles in the body: it is a key intermediate in the urea cycle, helping to eliminate ammonia, and it serves as an endogenous precursor to the amino acid L-Arginine [1, 3].
Unlike L-Arginine, which is heavily metabolized by the liver (first-pass metabolism), L-Citrulline bypasses the liver and is converted into L-Arginine in the kidneys. This makes L-Citrulline supplementation a more efficient method for increasing systemic L-Arginine levels and, consequently, boosting the production of Nitric Oxide (NO) [1, 3]. Nitric oxide is a powerful vasodilator that relaxes blood vessels, leading to improved blood flow, which is the primary mechanism behind many of L-Citrulline’s benefits.
Chemical Composition and Key Bioactive Compounds
L-Citrulline is available in two main supplemental forms, which differ in their composition and common applications.
| Form | Description |
|---|---|
| L-Citrulline | This is the pure, free-form version of the amino acid. It is primarily used for its benefits related to increasing nitric oxide production for cardiovascular health, such as improving blood pressure and blood flow [1]. |
| Citrulline Malate (CM) | This form combines L-Citrulline with malate (malic acid), an essential component of the Krebs cycle (TCA cycle), which is a key energy-producing pathway in the body. CM is the form most commonly used in sports nutrition supplements, with the theory that it may provide a dual benefit: the nitric oxide boost from citrulline and enhanced energy production from malate [1, 2]. The typical ratio is 2:1 (L-Citrulline to Malate). |
A 2018 review in Nutrients states: “Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis” [3].
Health Benefits
Research on L-Citrulline has focused on its cardiovascular effects and its potential as an ergogenic aid for exercise performance.
Cardiovascular Health (Blood Pressure & Blood Flow)
By increasing nitric oxide production, L-Citrulline helps relax and widen blood vessels, which can lead to lower blood pressure and improved circulation.
- Evidence: Supplementation with L-Citrulline has been shown to be a promising intervention for lowering blood pressure, particularly in individuals with pre-hypertension or hypertension. Studies show that consistent use for at least seven days can improve arterial function and reduce resting and stress-induced blood pressure by 4-15% [1, 3].
- The Verdict: L-Citrulline is a well-supported supplement for improving cardiovascular health, especially for individuals looking to manage blood pressure and enhance circulatory function.
Exercise Performance
Citrulline Malate is widely marketed as a performance-enhancing supplement, though the scientific evidence remains mixed.
- Evidence: The proposed benefits include reduced muscle soreness, improved ammonia clearance, and enhanced performance in high-intensity exercise. However, a 2021 critical review in the European Journal of Applied Physiology concluded that the results are equivocal and ambiguous [2]. While some studies using an acute 8-gram dose of CM show benefits, many do not. The inconsistencies are attributed to differences in study protocols, dosing strategies, and even the quality and ratio of the supplements used [2].
- The Verdict: The efficacy of Citrulline Malate for improving exercise performance is not definitively established. While theoretically promising, the real-world benefits are inconsistent across studies. More research is needed to determine optimal dosing and specific use cases.
Dosage and Usage
Dosage recommendations differ based on the form of citrulline and the intended goal.
- For Cardiovascular Health: A daily dose of 3–6 grams of L-Citrulline is recommended [1].
- For Exercise Performance: The most commonly studied dose is 8 grams of Citrulline Malate (in a 2:1 ratio, providing ~5.3 grams of L-Citrulline), taken approximately one hour before exercise [1, 2].
- Food Sources: The most famous natural source of L-Citrulline is watermelon. Other sources include pumpkins, cucumbers, and gourds [1].
Safety and Precautions
L-Citrulline is considered a very safe supplement with a high tolerability profile.
- General Safety: There are no known serious side effects associated with L-Citrulline supplementation. Unlike L-Arginine, it does not typically cause the same level of gastrointestinal distress at higher doses [1].
- Drug Interactions: While generally safe, individuals taking medications for blood pressure or erectile dysfunction (e.g., PDE5 inhibitors) should consult a healthcare provider before using L-Citrulline, as it may have additive effects on blood flow and blood pressure.
