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

Citrulline in health and disease. Review on human studies.

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Academic Department of Medical and Surgical Gastroenterology, Homerton University Hospital, London, UK. Electronic address:
Department of Surgery and Nutrition, Orłowski Hospital, Medical University of Warsaw, Warsaw, Poland.
Clinical Chemistry Department, Cochin Hospital AP-HP, Paris and EA4466, Faculty of Pharmacy, Paris Descartes University, Paris, France.
Norwich Medical School, University of East Anglia, Norwich, UK.


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.


Antioxidants; Citrulline; Nitric oxide; Sarcopenia


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