What is L-Citrulline?
This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article.Β L-Citrulline is a non-essential amino acid that plays a significant role in various physiological processes. It is naturally found in foods such as watermelon and is also produced in the body. This amino acid has garnered attention for its potential health benefits, particularly in enhancing exercise performance, improving cardiovascular health, and supporting metabolic functions. Other names include: 2-amino-5-(carbamoylamino)pentanoic acid, Citrulline, Citrulline Malate, L-Citrulina, L-Citrulline AKG, L-Citrulline-Alpha Ketoglutaric Acid, L-Citrulline Malate, Malate de Citrulline.
Chemical and Biological Properties
L-Citrulline is a neutral alpha-amino acid formed by enzymes in the mitochondria. It serves as a precursor to L-arginine, another amino acid that is crucial for the synthesis of nitric oxide (NO), a molecule that regulates blood flow and vascular function3. Unlike L-arginine, L-citrulline is not extensively metabolized in the gastrointestinal tract or liver, making it more effective at increasing L-arginine levels and NO synthesis6.
Health Benefits of L-Citrulline
Cardiovascular Health
L-Citrulline supplementation has shown promise in improving cardiovascular health. It enhances NO production, which helps in vasodilation and blood flow regulation. Studies have indicated that L-citrulline can lower blood pressure and provide endothelial protection, particularly in individuals with pre-hypertension or hypertension3. However, some studies have found no significant effects on blood pressure or arterial stiffness in older adults8.
Exercise Performance
L-Citrulline is widely recognized for its potential to enhance athletic performance. It improves oxygen uptake kinetics and reduces muscle fatigue, thereby enhancing endurance and performance in high-intensity exercises. For instance, supplementation with L-citrulline has been shown to improve cycling time trial performance and reduce completion time in trained athletes2 4 5. It also increases plasma L-arginine levels, which further supports NO production and muscle function2.
Metabolic and Muscle Health
L-Citrulline has been found to stimulate protein synthesis and improve muscle protein balance, making it beneficial for muscle health. This is particularly important in conditions like sarcopenia, where muscle mass and function decline with age10. Additionally, L-citrulline supplementation has been shown to enhance fetal growth and protein synthesis in models of intrauterine growth restriction, indicating its potential in supporting growth and development1.
Antioxidant and Anti-inflammatory Effects
L-Citrulline also exhibits antioxidant and anti-inflammatory properties. It modulates nitric oxide synthesis and enhances the antioxidant defense system, which can be beneficial in reducing oxidative stress and inflammation. This has been observed in studies involving laying hens, where L-citrulline supplementation improved antioxidant status and nitric oxide production7.
Clinical and Therapeutic Uses of L-Citrulline
Given its various health benefits, L-citrulline is being explored for its therapeutic potential in several clinical settings. It is used as a dietary supplement to support cardiovascular health, enhance exercise performance, and improve muscle function. Moreover, it serves as a biomarker for intestinal integrity and is being investigated for its role in managing conditions like rheumatoid diseases and cancer9.
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πͺCan L-Citrulline improve endurance and reduce muscle fatigue during high-intensity exercises?
Adverse Effects of L-Citrulline
No Significant Impact on Blood Pressure and Arterial Stiffness
Multiple studies have shown that L-Citrulline supplementation does not significantly affect blood pressure, pulse wave reflection, or arterial stiffness at rest or during exercise in older males and overweight individuals1 4 5.
No Effect on Oxidative Stress and Inflammatory Biomarkers
Systematic reviews and meta-analyses indicate that L-Citrulline does not significantly influence oxidative stress or inflammatory biomarkers in response to physical exercise6.
Potential Hepatoprotective Effects
In animal studies, L-Citrulline has shown hepatoprotective effects against dexamethasone-induced liver enzyme derangements, suggesting it may have protective rather than adverse effects on liver function2.
Thermoregulatory and Antioxidant Effects
In broilers, L-Citrulline supplementation helped regulate body temperature and enhanced antioxidant defense mechanisms under heat stress conditions, indicating potential benefits rather than adverse effects3.
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How has L-Citrulline Improved Patient Outcomes?
Improvement in Vascular Function and Endothelial Health
L-Citrulline supplementation has been shown to improve endothelial function, as evidenced by increased flow-mediated dilation (FMD) and FMD/NMD ratios in patients with coronary artery disease (CAD)10. Similar improvements in vascular function were observed in patients with heart failure with preserved ejection fraction (HFpEF)4.
Enhanced Exercise Performance and Oxygen Uptake
Supplementation with L-Citrulline improved oxygen uptake kinetics and high-intensity exercise performance in healthy adults8. Additionally, patients with HFpEF showed improved functional capacity, as measured by the six-minute walk test (6MWT)4.
Reduction in Inflammatory Markers and Improved Lipid Profile
L-Citrulline supplementation significantly reduced levels of high-sensitivity C-reactive protein (hs-CRP) and improved lipid profiles, including reductions in total cholesterol and low-density lipoprotein (LDL-C) in critically ill patients1. Similar reductions in inflammatory markers were observed in overweight and obese patients with type 2 diabetes (T2D)5 7.
Improved Glucose Homeostasis in Diabetic Patients
In patients with T2D, L-Citrulline supplementation led to significant reductions in fasting blood glucose, insulin levels, and hemoglobin A1c (HbA1c)5 7.
Enhanced Cardiac Function in Heart Failure Patients
Patients with systolic heart failure experienced significant improvements in left ventricular ejection fraction (LVEF) and overall functional class with L-Citrulline supplementation2.
Potential Benefits in Muscle Function and Energy Production
L-Citrulline has shown promise in improving muscle function and energy production in conditions like post-polio syndrome (PPS) and Duchenne muscular dystrophy (DMD)3 6.
Improvement in Erectile Function
In animal models, L-Citrulline supplementation improved erectile function by increasing nitric oxide production and enhancing smooth muscle/collagen ratios9.
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L-Citrulline Mechanisms of Action
Nitric Oxide (NO) Production and Vasodilation
L-Citrulline serves as a precursor to L-arginine, which is then converted to NO, a critical molecule for vasodilation and blood flow regulation3 4 5 8.
The vasodilatory effects of L-citrulline are mediated through NO- and prostaglandin-dependent pathways3 5.
Muscle Protein Synthesis
L-Citrulline enhances muscle protein synthesis and cell size, particularly under catabolic conditions, by increasing iNOS mRNA expression and subsequent NO production1 6.
It also stimulates protein synthesis in fetal muscle, which may contribute to improved fetal growth in cases of intrauterine growth restriction6.
Antioxidant and Anti-inflammatory Effects
L-Citrulline exhibits antioxidant properties by increasing the activity of enzymes like superoxide dismutase and catalase, and by reducing oxidative stress markers2 7.
It also has anti-inflammatory effects, as evidenced by the downregulation of inflammatory pathways such as the NF-ΞΊB pathway7.
Recycling and Metabolism
L-Citrulline is recycled back to L-arginine via the argininosuccinate synthetase and lyase pathway, which is crucial for sustained NO production4 9.
This recycling mechanism is active in various tissues, including the gastric fundus and pancreatic beta-cells, where it supports NO synthesis and related cellular functions4 9.
Thermoregulation and Stress Response
L-Citrulline helps in regulating body temperature and improving thermotolerance under heat stress conditions by modulating NO synthesis and antioxidant defenses2.
Cellular Uptake Mechanisms
The uptake of L-citrulline in intestinal epithelial cells involves both Na+-dependent and Na+-independent transport systems, which are distinct from those used for L-arginine transport10.
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Disclaimer
The content presented in this blog is generated by Consensus, an AI-powered academic search engine, and is based on publicly available scientific literature. While every effort is made to provide accurate, up-to-date, and well-researched information, the content is intended for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before making any decisions regarding medical conditions, treatments, or medications. The AI system’s analysis may not cover all perspectives, emerging research, or individual cases, and it is not a substitute for professional expertise. Neither the blog publisher nor the developers of the AI-powered search engine are responsible for any actions taken based on the information provided in this content. Use of this information is at your own risk. Citations to the original scientific studies are included for reference, but these studies should be reviewed in full and interpreted with the guidance of a healthcare or research professional.
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