Citrulline: pharmacological perspectives and its role as an emerging biomarker in future

Fundam Clin Pharmacol. 2013 Feb;27(1):35-50. doi: 10.1111/j.1472-8206.2012.01059.x. Epub 2012 Jul 31.


L-Citrulline is a naturally occurring non-essential amino acid, an intermediate in urea cycle and conditionally essential in intestinal pathology. It is a potent hydroxyl radical scavenger and much more effective precursor of arginine and nitric oxide (NO) than arginine itself so exploited in therapeutics. Plasma citrulline concentration is used by clinicians to assess functional enterocyte mass in various chronic and acute small bowel pathologies like short bowel syndrome that has become an indication in clinical practice. Its supplementation is likely to be used in conditions like erectile dysfunction, sickle cell anemia, short bowel syndrome (to restore nitrogen balance), hyperlipidemia, cancer chemotherapy, hypercholestremia, in hyperoxic lung damage, urea cycle disorders, Alzheimers disease, multi-infarct dementia and as an immunomodulator. Its emerging role as a biomarker in intestinal pathology and early diagnosis of Rheumatoid arthritis has spread considerable interest. Antibody detection to Anti-cyclic citrullinated peptide (ACCP) antibodies can be recommended for early detection of RA decreasing joint damage and deformity, because these are detected well before the onset of disease manifestations of RA. The test is highly specific than RF (Rheumatoid factor), with moderate sensitivity, but much useful in differentiating RA from other disorders. Further studies and exploration is required in these areas.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Citrulline / adverse effects
  • Citrulline / blood
  • Citrulline / metabolism*
  • Citrulline / therapeutic use
  • Dietary Supplements* / adverse effects
  • Enterocytes / metabolism
  • Free Radical Scavengers / adverse effects
  • Free Radical Scavengers / blood
  • Free Radical Scavengers / metabolism*
  • Free Radical Scavengers / therapeutic use
  • Humans
  • Kidney / metabolism
  • Liver / metabolism


  • Biomarkers
  • Free Radical Scavengers
  • Citrulline