L-Citrulline Clinical Evidence
Immunology Endocrine and Metabolic Agents in Medicinal Chemistry
Morita M, et al. Effects of oral L-Citrulline supplementation on lipoprotein oxidation and endothelial dysfunction in humans with vasospastic angina. 2013 Sep;13(3):214-220.
Topic:
Can supplementation with L-citrulline improve endothelial dysfunction?
Background:
Decreased nitric oxide (NO) bioavailability and increased lipid oxidation are linked to worsening endothelial dysfunction. L-citrulline has been shown to enhance NO signaling. Can it help improve endothelial function?
Study Type:
Human clinical intervention trial
Study Design:
Participants took 800 mg of L-citrulline daily for 8 weeks. Before, during, and after supplementation, researchers measured FMD, blood NOX, asymmetric dimethylarginine (ADMA), small dense LDL, oxidized lipids, and amino acid concentrations.
Subjects:
22 patients aged, 41-64, with vasospastic angina, diagnosed with flow-mediated dilation (FMD) of the brachial artery
Dosage:
800 mg/day, for 8 weeks
Results:
Compared to baseline, FMD was significantly improved at 4 weeks, 8 weeks, and 4 weeks after participants ceased supplementation. L-citrulline also significantly lowered plasma levels of ADMA. Arginine/ADMA ratios and NOX levels rose markedly, while serum levels of oxidized LDL, lectin-like oxidized LDL receptor 1 (LOX-1), and ligand-containing ApoB (LAB) (a marker of activity of oxidized lipoprotein binding to LOX-1) all fell.
Conclusions:
“L-citrulline supplementation improves endothelial dysfunction, probably due to potentiating NO-dependent reactions and decreasing the state of lipoprotein oxidation in humans.”
Fundamental and Clinical Pharmacology
Kaore SN, et al. Citrulline: pharmacological perspectives and its role as an emerging biomarker in future. 2013 Feb;2791):35-50.
Topic:
What are the clinical uses of citrulline?
Background:
Citrulline is a naturally occurring, non-essential amino acid that serves as a precursor to arginine and raises nitric oxide levels more effectively than arginine itself.
Study Type:
Review
Dosage:
N/A
Summary:
Citrulline may be used to treat:
• Erectile dysfunction
• Sickle cell anemia
• Short bowel syndrome (to restore nitrogen balance)
• Hyperlipidemia
• Hypercholesteremia
• Side effects from chemotherapy
• Hyperoxic lung damage
• Urea cycle disorders
• Alzheimer’s disease
• Multi-infarct dementia
• Immune issues
Testing citrulline levels can also help to detect Rheumatoid arthritis.
Conclusions:
“Further studies and exploration is required in these areas.”
Acta Physiologica
Bahadoran Z, et al. Endogenous flux of nitric oxide: citrulline is preferred to arginine. 2021 Mar;231(3):e13572.
Topic:
Which is a better supplement for increasing production of nitric oxide, arginine or citrulline?
Background:
Arginine and its precursor citrulline have received much attention over the past two decades because of arginine’s role in increasing the production of nitric oxide. However, using arginine as a supplement is of questionable usefulness because of its limited availability. Is citrulline a better option?
Study Type:
Review
Dosage:
N/A
Summary:
There are several problems with using supplemental arginine to increase nitric oxide.
• Only a limited amount of arginine gets into systemic circulation when it is taken orally.
• Supplemental arginine also leads to the production of the enzyme arginase, which breaks down arginine.
• It also reduces the uptake of citrulline and the conversion of any citrulline that’s present in the body to arginine.
All these actions make it less effective at raising arginine levels.
By contrast, citrulline is more effective.
• It is more available, better absorbed in the intestine, and more likely to be reabsorbed in the kidneys.
• At the cellular level, citrulline is easily converted to arginine.
• Finally, cells prefer to use it, especially in high-demand situations.
Conclusions:
“The available evidence strongly supports the concept that Cit leads to higher NO production and suggests that Cit may have a better therapeutic effect than Arg for NO-disrupted conditions.”
Mechanism of Action
Citrulline, a precursor of arginine, increases arginine in the body 2.3 times as effectively as taking arginine itself. By increasing available arginine, citrulline boosts production of nitric oxide, which in turn improves dilation of blood vessels, as measured by flow-mediated dilation (FMD). This dilation improves several aspects of cardiovascular health, including heart rate, vascular function, clotting response, blood pressure, and circulation. It also enhances athletic performance and erectile function.