Citrulline in health and disease. Review on human studies

Abstract

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.

Quantitative analysis of amino acids in human and bovine colostrum milk samples through iTRAQ labeling

“…Specifically, citrulline (CIT) and 1‐MHIS contents were ca 10‐ and 18‐fold higher respectively in human colostrum than in bovine colostrum. 1‐MHIS is a sensory neurotransmitter involved in signal transduction between peripheral nerves, and CIT participates in the uric acid cycle and is involved in scavenging free radicals, relaxing blood vessels, stabilizing blood pressure, and antioxidation . Our analyses indicated that the total content of free amino acids was 0.32 g L −1 and 0.63 g L −1 in bovine and human colostrum respectively.…”

“…1-MHIS is a sensory neurotransmitter involved in signal transduction between peripheral nerves, 43 and CIT participates in the uric acid cycle and is involved in scavenging free radicals, relaxing blood vessels, stabilizing blood pressure, and antioxidation. 44 Our analyses indicated that the total content of free amino acids was 0.32 g L −1 and 0.63 g L −1 in bovine and human colostrum respectively. These results highlighting the differences in individual amino acid content between bovine and human colostrum contribute to a comprehensive and in-depth understanding of bovine and human milk.…”

Correlation of plasma metabolites with glucose and lipid fluxes in human insulin resistance

“…The amino acid is not secreted by the liver, but the amount found in plasma has been shown to originate from production by enterocytes. 21 Via its product arginine, citrulline is important in the metabolism of nitric oxide (NO), a signalling molecule critical for the cardiovascular system as a vasodilatator. 22 Oral supplementation of citrulline is more potent at increasing serum arginine, and thus NO levels, than arginine itself due to a first-pass extraction effect by arginase in the gastro-intestinal tract, which does not affect citrulline.…”

Effects of Citrulline Supplementation on Body Weight in Patients With Hepatobiliary Pancreatic Surgery

“…Although results are inconsistent, a number of studies have focused on the impact of citrulline on performance in exercise and muscle strength . Citrulline is an amino acid, the precursor to arginine, which has been studied for possible effects including as an antioxidant and vasodilator, restoring nitrogen balance, improving muscle protein level, and preserving anti‐inflammatory mediator response . In addition, accumulating evidence suggests citrulline as a marker for surgical outcome and intestinal dysfunction .…”

“…4,5 Citrulline is an amino acid, the precursor to arginine, which has been studied for possible effects including as an antioxidant and vasodilator, restoring nitrogen balance, improving muscle protein level, and preserving anti-inflammatory mediator response. [6][7][8] In addition, accumulating evidence suggests citrulline as a marker for surgical outcome and intestinal dysfunction. 9,10 However, there are no reports of the impact of the consumption of citrulline in patients with hepatobiliary and pancreatic surgery.…”