What is citrulline?

Citrulline is a nonessential amino acid, which can be produced in your body from one of the 2 amino acids–arginine or ornithine–, so you do not need to get it from foods in order to be healthy [1]. Citrulline is a nonproteinogenic amino acid, which means it is not regularly incorporated into proteins [1].

Citrulline name origin: from the Latin citrullus = watermelon, from which it was first isolated [1].

Citrulline Functions in the Human Body

Citrulline is [1]:

  • A precursor of the amino acid arginine
  • A source of nitric oxide, which dilates arteries
  • A part of certain proteins
  • An ammonia scavenger

Citrulline in Foods

Citrulline can be found in the watermelon rind–the white part between the shell and meat [4].

Citrulline Supplements

Oral forms available without prescription (over-the-counter):

  • L-citrulline
  • L-citrulline monohydrate
  • L-citrulline ethyl ester HCl
  • Citrulline malate

Citrulline Health Benefits

Citrulline is POSSIBLY EFFECTIVE in treatment of the hereditary metabolic disorders hyperammonaemia-hyperornithinaemia-homocitrullinuria syndrome [5] and lysinuric protein intolerance [5].

There is INSUFFICIENT EVIDENCE [2] about the effectiveness of L-citrulline supplements in the prevention or treatment of high blood pressure after surgery in children or sickle cell disease, in increasing exercise performance or reducing muscle fatigue and soreness after the exercise [3].

Citrulline Safety: Side Effects, Toxicity

Citrulline supplements in recommended doses are POSSIBLY SAFE for most adults and children [2]. Allergies to citrulline supplements are possible.

Not much is known about citrulline supplements safety during pregnancy and breastfeeding, so women in these periods should avoid them [2].


Citrullinemia is a hereditary metabolic disorder with a buildup of citrulline and ammonia in the blood [6].

Symptoms, which may develop shortly after birth or only later in childhood or adulthood, may include vomiting, lethargy, poor appetite, seizures and, if not treated, coma and death [6]. 

Diagnosis is made by finding high blood ammonia and citrulline and low arginine levels, and increased urine orotic acid levels [6].

Treatment includes a life-long low-protein diet and certain nutrients and drugs [7].

  1. L-citrulline  PubChem
  2. L-citrulline  WebMD
  3. Bendahan D et al, 2002, Citrulline/malate promotes aerobic energy production in human exercising muscle  PubMed Central
  4. Rimando AM et al, 2005, Determination of citrulline in watermelon rind  PubMed
  5. van Vliet D et al, 2014, Single amino acid supplementation in aminoacidopathies: a systematic review  PubMed Central
  6. Citrullinemia  Genetics Home Reference
  7. Citrullinemia treatment and management  Emedicine

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