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Citrulline and the Intestine

Fragkos, K; (2018) Citrulline and the Intestine. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Citrulline, a non-protein amino acid, has been playing an important role in scientific research over the last few years. This thesis explores various aspects of citrulline with respect to intestinal disease, short bowel syndrome and intestinal failure. The first important finding was that citrulline as a term has been used at the end of the 19th century-beginning of the 20th century to describe an extract of the C. colocynthis, used as a subcutaneous laxative. Also, old sources have revealed that citrulline was first described as an amino acid by Koga and Ohtake (1914) and not by Wada (1930a). From the systematic review and meta-analysis, citrulline levels are strongly positively correlated with small bowel length in short bowel syndrome patients and strongly negatively correlated with intestinal disease severity with regards to enteropathies (coeliac disease, tropical enteropathy, mucositis, acute rejection in intestinal transplantation, but not Crohn’s disease). Citrulline cut-off levels have an overall sensitivity and specificity of 80% and citrulline levels compared to controls were reduced by 10 μmol/L. These findings suggest that citrulline is a marker of possible acute intestinal injury or intestinal insufficiency. Next, an original five-by-five cross-over study was designed (Williams design) comparing post-absorptive amino acid concentrations after challenges with citrulline, arginine, glutamine, 3-methyl-hisitidine and placebo. Citrulline was the most potent stimulator for all other amino acids, contrary to beliefs of glutamine challenges. Citrulline challenges could be useful in intestinal failure but also in liver failure where urea cycle pathways including glutamine, arginine and ornithine are implicated. The final study was an investigation of quality of life in short bowel syndrome patients. The quality of life scale is highly reliable in short bowel syndrome patients (Cronbach’s alpha > 0.700) and the main causes of low quality of life are fatigue, diarrhoea/increased stomal output, lack of sleep, gastrointestinal symptoms, and muscle pains.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Citrulline and the Intestine
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10047511
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