Citrulline in health and disease. Review on human studies

Clin Nutr. 2018 Dec;37(6 Pt A):1823-1828. doi: 10.1016/j.clnu.2017.10.009. Epub 2017 Oct 16.


The amino acid L-citrulline (CIT) is safely used from the neonatal period onwards in those with urea cycle defects and carbamyl phosphate synthetase or ornithine transcarbamylase deficiencies, but several lines of enquiry indicate that it might have a much wider therapeutic role. When protein intake is low and there is a catabolic state, endogenous arginine (ARG) synthesis cannot fully be met and its supplementation can prove challenging, particularly in patients with critical and multisystem illness. Supplementary CIT could constitute a safer but still focused means of delivering ARG to endothelial and immune cells as CIT is efficiently recycled into these cells and as kidneys can convert CIT into ARG. Unlike ARG, CIT is efficiently transported into enterocytes and bypasses liver uptake. It also appears to prevent excessive and uncontrolled nitric oxide (NO) production. Animal studies and early human data indicate positive effects of CIT on protein synthesis, in which its contribution is thought mediated through the mTOR pathway. It appears that CIT is an anabolic pharmaconutrient that can be safely administered even in critically ill patients. Promising results in cardiovascular diseases and in disease-related malnutrition can now be considered sufficient to justify formal clinical exploration in these areas and in sarcopenia in general.

Keywords: Antioxidants; Citrulline; Nitric oxide; Sarcopenia.

Publication types

  • Review

MeSH terms

  • Anabolic Agents
  • Animals
  • Arginine / administration & dosage
  • Arginine / metabolism
  • Athletic Performance
  • Carbamoyl-Phosphate Synthase I Deficiency Disease / drug therapy
  • Cardiovascular Diseases / drug therapy
  • Citrulline / administration & dosage
  • Citrulline / therapeutic use*
  • Endothelial Cells / metabolism
  • Enterocytes / metabolism
  • Female
  • Humans
  • Immunity / drug effects
  • Male
  • Ornithine Carbamoyltransferase
  • Ornithine Carbamoyltransferase Deficiency Disease / drug therapy
  • Oxidative Stress / drug effects
  • Protein Biosynthesis / drug effects
  • Urea Cycle Disorders, Inborn / drug therapy


  • Anabolic Agents
  • Citrulline
  • Arginine
  • Ornithine Carbamoyltransferase