citrulline
Citrulline (name derived from citrullus, the Latin word for watermelon, from which it was first isolated) is an amino acid. It is made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by nitric oxide synthase (NOS) family. Citrulline supplements have been claimed to promote energy levels, stimulate the immune system and help detoxify ammonia (a cell toxin). Citrulline is not involved in protein synthesis. Several pharmacokinetic studies have confirmed that citrulline is efficiently absorbed when administered orally. Oral citrulline could be used to deliver arginine to the systemic circulation or as a protein anabolic agent in specific clinical situations (for example in case of malnourishment), because recent data have suggested that citrulline, although not a component of proteins, stimulates protein synthesis in skeletal muscle through the mammalian target of rapamycin signaling pathway. Citrulline is converted to L-arginine by argininosuccinate synthase. L-arginine is in turn responsible for citrulline's therapeutic effects. Many of L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide (NO). — NCATS
Clinical trial activity
85 trials · 72 clinical orgs · 0 marketing orgs
Earliest trial started Oct 1, 2001 (NCT00223730)
Timeline
Indications
Approved for
Studied for
- Acute Lung Injury · Phase 3
- Aging · Phase 1
- Anemia, Sickle Cell · Phase 3
- Arterial Occlusive Diseases · Phase 1/Phase 2
- Asthma · Phase 2
- Blood Pressure · Phase 1
- Bronchopulmonary Dysplasia · Phase 1
- Cardiovascular Diseases · Phase 1/Phase 2
- Coronary Disease · Early Phase 1
- Diabetes Mellitus, Type 2 · Phase 1
- Eisenmenger Complex · Early Phase 1
- Ethnic and Racial Minorities · Early Phase 1
- Familial Primary Pulmonary Hypertension · Early Phase 1
- Fetal Growth Retardation · Phase 4
- Healthy Volunteers · Phase 1
- Heart Defects, Congenital · Phase 3
- Heart Diseases · Phase 1/Phase 2
- Heart Failure · Phase 1
- Heart Failure, Diastolic · Phase 1
- Heart Septal Defects, Atrial · Phase 3
- Heart Septal Defects, Ventricular · Phase 3
- Hypertension · Phase 1/Phase 2
- Hypertension, Pregnancy-Induced · Phase 1
- Hypertension, Pulmonary · Phase 3
- Hypertrophy, Left Ventricular · Phase 3
- Infant, Premature · Early Phase 1
- Infant, Premature, Diseases · Phase 1
- Inflammation · Phase 1
- Intermittent Claudication · Phase 2
- Intestinal Failure · Phase 3
- Malnutrition · Phase 3
- MELAS Syndrome · Phase 1
- Multiple Organ Failure · Phase 3
- Muscular Dystrophies · Phase 2
- Muscular Dystrophy, Duchenne · Phase 3
- Neoplasms · Phase 2
- Obesity · Phase 2
- Pain · Phase 2
- Peripheral Arterial Disease · Phase 2
- Postpoliomyelitis Syndrome · Phase 3
- Pre-Eclampsia · Phase 2/Phase 3
- Pregnancy · Phase 2/Phase 3
- Premature Birth · Phase 1
- Pulmonary Disease, Chronic Obstructive · Phase 3
- Respiratory Insufficiency · Phase 2
- Sepsis · Phase 3
- Vascular Diseases · Early Phase 1
Mechanism of action
- Unspecified targetSupplementation
supplementation
Chemistry & pharmacology
SMILES
N[C@@H](CCCNC(N)=O)C(O)=O- Mol. weight
- 175.1857 g/mol
Oral
No
Parenteral
No
Topical
No
Sources
- WikipediaCitrulline ↗
- NCATS29VT07BGDA ↗
Also known as
- 2-amino-5-ureidovaleric acid
- 2-amino-5-ureidovaleric acid
- 9.5 s alpha(1)-glycoprotein alpha(1)-glycoprotein
- alpha-amino-delta-ureidovaleric acid
- alpha-amino-delta-ureidovaleric acid
- cirulline
- cit
- cit
- cit
- citrulline
- citrulline
- citrulline
- citrulline
- citrulline
- citrulline malate
- citrulline malate
- delta-ureidonorvaline
- delta-ureidonorvaline
- l-2-amino-5-ureidovaleric acid
- l-2-amino-5-ureidovaleric acid
- l-citrulline
- l-citrulline
- l-citrulline
- l-citrulline
- l-citrulline malate
- n(5)-(aminocarbonyl)-l-ornithine
- n(5)-(aminocarbonyl)-l-ornithine
- n5-(aminocarbonyl)ornithine
- n5-(aminocarbonyl)ornithine
- n5-carbamoyl-l-ornithine
- n5-carbamoyl-l-ornithine
- n5-carbamoylornithine
- n5-carbamoylornithine
- n(delta)-carbamylornithine
- n(delta)-carbamylornithine
- (s)-2-amino-5-ureidopentanoic acid
- (s)-2-amino-5-ureidopentanoic acid
- serum p-component
- sigma-ureidonorvaline
- α-amino-δ-ureidovaleric acid
- α-amino-δ-ureidovaleric acid
- δ-ureidonorvaline
- δ-ureidonorvaline
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT06989567 | Phase 3 | Jul 25, 2025 | Asklepion |
| NCT06426147 | N/A | Jan 1, 2025 | University of Barcelona |
| NCT06635902 | Phase 2 | Nov 30, 2024 | Georgetown University, National Heart, Lung, and Blood Institute (NHLBI) |
| NCT05259904 | Phase 2 | Apr 30, 2024 | Department of Defense, University of Colorado, Denver |
| NCT06212765 | Phase 3 | Jan 25, 2024 | University of Grenoble |
| NCT05934318 | N/A | Sep 30, 2023 | Kenya Medical Research Institute, Telethon Kids Institute, University of Liverpool, University of Toronto |
| NCT06025383 | N/A | Jul 20, 2023 | Texas Tech University |
| NCT05722860 | Phase 1 | May 3, 2023 | University of Oklahoma |
| NCT06016478 | N/A | May 1, 2023 | Texas Tech University |
| NCT05778266 | N/A | Mar 14, 2023 | Universidad de Guanajuato |
| NCT05636397 | N/A | Feb 28, 2023 | University of Toronto |
| NCT06025357 | N/A | Jan 1, 2023 | Texas Tech University |
| NCT05974813 | N/A | Jan 1, 2023 | European University Cyprus |
| NCT05525871 | N/A | Aug 15, 2022 | Universidad Católica San Antonio de Murcia |
| NCT05253209 | Phase 3 | Jun 29, 2022 | Asklepion, Indiana University |
| NCT05183893 | N/A | Feb 15, 2022 | University of Granada |
| NCT05029778 | Phase 4 | Oct 20, 2021 | University of Guadalajara |
| NCT04513288 | N/A | Sep 1, 2021 | University of Rennes |
| NCT04979793 | Phase 1 | Jul 28, 2021 | University of Texas, Galveston |
| NCT04770155 | Early Phase 1 (Phase 1) | May 27, 2021 | University of Mississippi |
Organizations
Research & Development (72)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Asklepion | For profit | 7 | 7 | 2 | 2006 |
| Texas Tech University | Academic/Hospital | 7 | 7 | 1 | 2015 |
| University of Mississippi | Academic/Hospital | 5 | 4 | 2 | 2010 |
| University of Pittsburgh | Academic/Hospital | 5 | 3 | 3 | 2006 |
| Vanderbilt University | Academic/Hospital | 5 | 4 | 3 | 2001 |
| Florida State University | Academic/Hospital | 4 | 4 | 2 | 2011 |
| National Institutes of Health (NIH) | Government | 4 | 0 | 2 | 2010 |
| University of Grenoble | Academic/Hospital | 4 | 4 | 2 | 2015 |
| Baylor University | Academic/Hospital | 3 | 3 | 2 | 2009 |
| Maastricht University | Academic/Hospital | 3 | 3 | 2 | 2010 |
| National Heart, Lung, and Blood Institute (NHLBI) | Government | 3 | 0 | 1 | 2003 |
| Shahid Beheshti University of Medical Sciences | Academic/Hospital | 3 | 1 | 2 | 2012 |
| University of Basel | Academic/Hospital | 3 | 0 | 2 | 2013 |
| University of Bern | Academic/Hospital | 3 | 2 | 2 | 2013 |
| University of Colorado, Denver | Academic/Hospital | 3 | 3 | 2 | 2017 |
| University of Nantes | Academic/Hospital | 3 | 3 | 2 | 2008 |
| University of Rennes | Academic/Hospital | 3 | 3 | 1 | 2016 |
| Angiogenix | For profit | 2 | 2 | 2 | 2006 |
| Kyowa Hakko Kogyo | For profit | 2 | 0 | 1 | 2009 |
| Masih Daneshvari Hospital | Academic/Hospital | 2 | 2 | 1 | 2012 |