From the Guidelines
L-citrulline is generally considered safe for most adults when taken as a supplement at recommended doses, typically ranging from 3-6 grams daily. This amino acid occurs naturally in foods like watermelon and is produced by the body. It's well-tolerated with minimal side effects, though some people may experience mild digestive discomfort, heartburn, or changes in urination patterns. L-citrulline works by converting to l-arginine in the kidneys, which then produces nitric oxide that helps relax blood vessels. This mechanism explains its popularity for improving blood flow, exercise performance, and cardiovascular health. However, pregnant or breastfeeding women should avoid supplementation due to insufficient safety data. People with certain medical conditions, particularly those affecting kidney or liver function, should consult healthcare providers before use. Similarly, those taking medications like nitrates, erectile dysfunction drugs, or blood pressure medications should seek medical advice due to potential interactions that could cause dangerous drops in blood pressure. The supplement's effects may take several weeks to become noticeable, and quality varies between manufacturers, so choosing reputable brands is important. According to a recent study 1, L-arginine, which is closely related to L-citrulline, should be held 24 hours before surgery due to its potential to increase intraoperative hypotension, but this does not necessarily imply a safety concern for general use.
Some key points to consider when taking L-citrulline supplements include:
- Starting with a low dose and gradually increasing as needed and under medical supervision
- Monitoring blood pressure and kidney function, especially in individuals with pre-existing conditions
- Being aware of potential interactions with other medications
- Choosing a high-quality supplement from a reputable manufacturer
- Consulting with a healthcare provider before use, especially for pregnant or breastfeeding women, and individuals with certain medical conditions. It's also important to note that while L-citrulline may have benefits for exercise performance and cardiovascular health, more research is needed to fully understand its effects, as seen in studies on L-arginine supplementation in patients with pulmonary arterial hypertension 1.
From the Research
Safety of L-Citrulline Supplementation
- L-citrulline is a naturally occurring non-essential amino acid that has been shown to be safe for use in various conditions, including urea cycle defects and intestinal pathology 2.
- Studies have demonstrated that L-citrulline supplementation can be safely used in patients with critical and multisystem illness, as it is efficiently recycled into endothelial and immune cells and can prevent excessive and uncontrolled nitric oxide production 3.
- A systematic review and meta-analysis of randomized controlled trials found that L-citrulline supplementation significantly reduced systolic and diastolic blood pressure, with no reported adverse effects 4.
Therapeutic Uses of L-Citrulline
- L-citrulline has been shown to have potential therapeutic benefits in various conditions, including cardiovascular disease, erectile dysfunction, sickle cell anemia, and cancer chemotherapy 2, 5.
- Supplementation with L-citrulline has been found to improve nitric oxide production and cardiovascular function in patients with endothelial dysfunction 5, 6.
- L-citrulline may also have benefits for muscle and metabolic health, particularly in older populations 6.
Pharmacological Perspectives
- L-citrulline is a potent hydroxyl radical scavenger and a more effective precursor of arginine and nitric oxide than arginine itself 2.
- Unlike arginine, L-citrulline is not metabolized in the intestine or liver and does not induce tissue arginase, making it a more effective therapeutic agent 5.
- L-citrulline can be readily converted to arginine in the kidney, vascular endothelium, and other tissues, enhancing nitric oxide production 5, 3.