Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection

Abstract

Objective: Arginine supplementation seems logical in situations where this amino acid becomes essential, for example after massive intestinal resection. Arginine is taken up and metabolised by the liver to a large extent and its supplementation is potentially unsafe. Citrulline is not captured by the liver and passes freely to the kidneys where it is metabolised to arginine, and so is a good candidate to generate arginine and thereby improve nutritional status. Methods: Twenty four rats were assigned to four groups: citrulline, arginine, control, and sham. The sham group underwent transection and the three other groups resection of 80% of the small intestine. All rats were fed by enteral nutrition and its composition was as follows: supplementation with citrulline in the citrulline group, supplementation with arginine in the arginine group, and standard polymeric enteral nutrition in the control and sham groups. All groups received isonitrogenous nutrition and citrulline and arginine intakes were equimolar in their respective groups. After 10 days, the rats were sacrificed. Results: Arginine concentration was higher (p,0.05) in plasma and muscle in the citrulline group than in the three other groups. Plasma levels of arginine were 110 (12), 79 (7), 167 (22), and 228 (13) Citrulline preserved nitrogen balance in resected rats but not in arginine supplemented rats (mean J10: 2.27 (0.29), 1.67 (0.15), 1.98 (0.29), and 2.43 (0.41) g/24 hours in the sham, control, arginine, and citrulline groups, respectively). Conclusion: Supplementing the diet with citrulline is a very efficient means of increasing arginine levels and improving nitrogen balance after massive intestinal resection. The results of this study form a strong rationale for citrulline supplementation in these patients.

l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans

“…Thereafter, the bulk of plasma Cit is converted to Arg, mostly in the kidneys (15,24,59,65,70), but also in several other tissues (15,23,70). This is compatible with the significant increase in plasma [Arg] in this study and several previous studies (32,47,53,62) following Cit supplementation. It is important to note that not only does Cit increase systemic [Arg] by avoiding catabolism along the intestinal-renal axis, but Cit might also be expected to enhance Arg bioavailability, given that Cit can function as an allosteric inhibitor of arginase (54).…”

“…This is supported by our finding of a lower plasma [Orn], the product of Arg metabolism by arginase (70), after Cit than Arg supplementation in this study. However, despite this potential for greater systemic Arg bioavailability following oral Cit than oral Arg supplementation and in contrast to previous studies reporting a greater increase in plasma [Arg] after Cit than Arg ingestion (32,47,53,62), plasma [Arg] was increased by a similar magnitude when the same dose of Cit and Arg was orally administered in this study. These conflicting findings might be a function of between-study differences in the experimental subjects and supplementation regimens.…”

“…Synthesis of Arg from Cit is prevalent in other tissues (15,23,70), and this process is facilitated since Cit does not compete with ADMA for cell transport (50, 69). Importantly, it has been shown that oral Cit supplementation more effectively increases the circulating (32,47,53,62) and tissue (63) [Arg] than an equivalent dose of Arg and that Cit supplementation can increase NOS activation (63) and NO biomarkers (46, 53). …”

Two weeks of watermelon juice supplementation improves nitric oxide bioavailability but not endurance exercise performance in humans

“…Although traditionally recognised as a product of the nitric oxide synthase-mediated oxidation of L-arginine [3], recent evidence suggests that L-citrulline can be recycled back to L-arginine [17] and is more effective than orally ingested L-arginine at increasing systemic [18,19] and muscle [20] L-arginine.…”

Biomarkers for radiation-induced small bowel epithelial damage: An emerging role for plasma Citrulline

“…Intestinal dysfunction resulting from intestinal diseases or injuries affect intermediary and inter-organ metabolism [83][84][85] . Hence, any factor affecting the intestinal mucosal cell mass will have an impact on protein and amino acid metabolism [83,[86][87][88][89][90] . Since the pioneering work of Windmueller and Spaeth during the 1970's many research groups have demonstrated that amino acids are the major fuel for the small bowel epithelium, both under conditions of fasting and feeding [91][92][93][94][95][96][97] .…”