Citrulline is an intermediate, nonprotein-forming amino acid in the urea cycle serving as a precursor to arginine. It derives its name from the watermelon (Citrullus vulgaris), where it was first isolated and identified. It is easily absorbed by the gut and bypasses the liver, making it an effective method for repleting arginine.
Other food sources of citrulline include muskmelons, bitter melons, squashes, gourds, cucumbers and pumpkins. Citrulline can also be synthesized from arginine and glutamine in enterocytes, which can then be metabolized by the kidneys back into arginine. Because citrulline is produced in enterocytes, it has been proposed as a marker of enterocyte mass in conditions of villous atrophy.
Given the importance of arginine in nitric oxide production for vasodilation and muscle protein synthesis, citrulline is sometimes administered therapeutically to deliver arginine to endothelial and immune cells. It is also supplemented in sarcopenia to stimulate protein synthesis in skeletal muscle through the rapamycin (mTOR) pathway. Citrulline supplementation has been studied in conditions like erectile dysfunction, sickle cell anemia, short bowel syndrome, hyperlipidemia, cancer chemotherapy, urea cycle disorders, Alzheimer’s disease, multi-infarct dementia, and as an immunomodulator.
References:
- Bahri S, Zerrouk N, Aussel C, et al. Citrulline: from metabolism to therapeutic use. Nutrition. 2013;29(3):479-484.
- Allerton TD, Proctor DN, Stephens JM, Dugas TR, Spielmann G, Irving BA. l-Citrulline Supplementation: Impact on Cardiometabolic Health. Nutrients. 2018;10(7).
- Kaore SN, Amane HS, Kaore NM. Citrulline: pharmacological perspectives and its role as an emerging biomarker in future. Fundament Clin Pharmacol. 2013;27(1):35-50.
- Cynober L, Moinard C, De Bandt JP. The 2009 ESPEN Sir David Cuthbertson. Citrulline: a new major signaling molecule or just another player in the pharmaconutrition game? Clin Nutr. 2010;29(5):545-551.
- Crenn P, Vahedi K, Lavergne-Slove A, Cynober L, Matuchansky C, Messing B. Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology. 2003;124(5):1210-1219.
- Crenn P, Hanachi M, Neveux N, Cynober L. [Circulating citrulline levels: a biomarker for intestinal functionality assessment]. Ann Biol Cliniq. 2011;69(5):513-521.
- Papadia C, Osowska S, Cynober L, Forbes A. Citrulline in health and disease. Review on human studies. Clin Nutr. 2018;37(6 Pt A):1823-1828.
- Rouge C, Des Robert C, Robins A, et al. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol. 2007;293(5):G1061-1067.
- Thibault R, Flet L, Vavasseur F, et al. Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, doubleblind, cross-over study. Clin Nutr. 2011;30(6):807-811.
- Jurgens P, Schwartau M, Doehn M. [Disorders of amino acid metabolism in a patient with identified thiamine deficiency]. Infusionstherapie klinische Ernahrung. 1982;9(6):312-316.
Low citrulline may be secondary to a relatively low protein diet and/or intestinal malabsorption. Because citrulline can be formed from glutamine, glutamine depletion has been associated with low citrulline levels in plasma.
Understand and improve your laboratory results with our health dashboard.
Upload your lab reports and get your interpretation today.
Our technology helps to understand, combine, track, organize, and act on your medical lab test results.
Elevated citrulline can occur with urea cycle defects. Lack of nutrient cofactors or enzymatic SNPs within the urea cycle can contribute to elevated citrulline levels. Citrullinemia is an inherited autosomal recessive disease that affects the enzyme arginosuccinate synthase and is diagnosed in infancy. In most cases, a serious problem related to citrulline is unlikely and may be a limitation in the cofactors associated with citrulline metabolism: aspartic acid and magnesium.
Elevated plasma levels may result from citrulline supplementation. Orally administered citrulline is highly bioavailable since plasma levels rise dramatically, whereas urinary citrulline loss is minimal. Elevated citrulline in urine can be a consequence of a urinary tract infection where bacterial action reduces arginine and produces citrulline. Administration of thiamine (vitamin B1) has been found to lower elevated citrulline, as well as other amino acids, in thiamine deficiency.
Interpret Your Lab Results
Upload your lab report, and we'll interpret and provide you with recommendations today.
Get StartedMonthly plan
Annual plan
Own it for life
Our exclusive data entry service is a convenient way to get your results into your private dashboard. Simply attach an image or a file of your lab test results, and one of our qualified data entry team members will add the results for you. We support all sorts of files, whether PDFs, JPGs, or Excel. This service is excellent whether you have a lot of reports to upload or are too busy to do the data entry yourself.
We strive to make the data entry process easy for you. Whether by offering dozens of templates to choose from that pre-populate the most popular laboratory panels or by giving you instant feedback on the entered values. Our data entry forms are an easy, fast, and convenient way to enter the reports yourself. There is no limit on how many lab reports you can upload.
$15 /month
billed every month
Most popular
Data entry included
$79 /year
$6.60/month billed annually
Data entry included
$250 /once
own it for life
Are You a Health Professional?
Get started with our professional plan
Welcome to Healthmatters Pro.
Save time on interpreting lab results with the largest database of biomarkers online. In-depth research on any test at your fingertips, all stored and tracked in one place. Learn more
Pro Monthly Plus
for health professionals
$75 per month
At HealthMatters, we're committed to maintaining the security and confidentiality of your personal information. We've put industry-leading security standards in place to help protect against the loss, misuse, or alteration of the information under our control. We use procedural, physical, and electronic security methods designed to prevent unauthorized people from getting access to this information. Our internal code of conduct adds additional privacy protection. All data is backed up multiple times a day and encrypted using SSL certificates. See our Privacy Policy for more details.
% Omega-3s, % Omega-6s, % Omega-9s, % Saturated Fats, 1-Methylhistidine, 3-Hydroxyisovaleric Acid, 3-Hydroxyphenylacetic Acid, 3-Hydroxypropionic Acid, 3-Methyl-4-OH-phenylglycol, 3-Methylhistidine, 4-Hydroxyphenylacetic Acid, 5-OH-indoleacetic Acid, 8-OHdG (urine), a-Amino-N-butyric Acid, a-Aminoadipic Acid, a-Hydroxybutyric Acid, a-Hydroxyisobutyric Acid (from MTBE), a-Keto-b-Methylvaleric Acid, a-Ketoadipic Acid, a-Ketoglutaric Acid, a-Ketoisocaproic Acid, a-Ketoisovaleric Acid, a-Ketophenylacetic Acid (from Styrene), a-Linolenic (ALA) 18:3 n3, AA / EPA (20:4 n6 / 20:5 n3), Adipic Acid, Alanine, Aluminum, Anserine (dipeptide), Antimony, Arachidic C20:0, Arachidonic (AA) 20:4 n6, Arginine, Arsenic, Asparagine, Aspartic Acid, b-Alanine, b-Aminoisobutyric Acid, b-OH-b-Methylglutaric Acid, b-OH-Butyric Acid, Barium, Behenic C22:0, Benzoic Acid, Bismuth, Cadmium, Calcium, Carnosine (dipeptide), Cesium, Chromium, cis-Aconitic Acid, Citramalic Acid, Citric Acid, Citrulline, Cobalt, Copper, Creatinine, Creatinine Concentration (Amino Acids FMV), Cystathionine, Cysteine, Cystine, D-Arabinitol, Dihomo-g-linolenic (DGLA) 20:3 n6, Dihydroxyphenylpropionic Acid (DHPPA), Docosahexaenoic (DHA) 22:6 n3, Docosapentaenoic (DPA) 22:5 n3, Docosatetraenoic (DTA) 22:4 n6, Eicosadienoic 20:2 n6, Eicosapentaenoic (EPA) 20:5 n3, Elaidic 18:1 n9t, Ethanolamine, Formiminoglutamic Acid (FIGlu), g-Aminobutyric Acid, g-Linolenic (GLA) 18:3 n6, Gadolinium, Gallium, Glutamic Acid, Glutamine, Glutaric Acid, Glyceric Acid, Glycine, Glycolic Acid, Hippuric Acid, Histidine, Homovanillic Acid, Indoleacetic Acid, Iron, Isocitric Acid, Isoleucine, Isovalerylglycine, Kynurenic / Quinolinic Ratio, Kynurenic Acid, Lactic Acid, Lead, Leucine, Lignoceric C24:0, Linoleic (LA) 18:2 n6, Linoleic / DGLA (18:2 n6 / 20:3 n6), Lipid Peroxides (urine), Lithium, Lysine, Magnesium, Malic Acid, Manganese, Margaric C17:0, Mercury, Methionine, Methylmalonic Acid, Molybdenum, Nervonic 24:1 n9, Nickel, Niobium, Oleic 18:1 n9, Omega-3 Index, Omega-6s /Omega-3s, Ornithine, Orotic Acid, Oxalic Acid, Palmitic C16:0, Palmitoleic 16:1 n7, Pentadecanoic C15:0, Phenylacetic Acid, Phenylalanine, Phosphoethanolamine, Phosphoserine, Platinum, Potassium, Proline, Pyroglutamic Acid, Pyruvic Acid, Quinolinic Acid, Rubidium, Sarcosine, Selenium, Serine, Stearic C18:0, Strontium, Suberic Acid, Succinic Acid, Sulfur, Tartaric Acid, Taurine, Thallium, Thorium, Threonine, Tin, Tricosanoic C23:0, Tryptophan, Tungsten, Tyrosine, Uranium, Urea, Urine Creatinine, Vaccenic 18:1 n7, Valine, Vanadium, Vanilmandelic Acid, Xanthurenic Acid, Zinc