From the desk of Dr. Nancy Collins, PhD, RDN, LD, NWCC, FAND
You may have noticed that one of the major ingredients in Expedite™ is the amino acid citrulline. While you probably are familiar with arginine, you might not be as familiar with citrulline. Citrulline is a nonessential amino acid, meaning the body can synthesize it endogenously. The function of citrulline is to produce arginine, which is why it is linked to wound healing and why it is added to the Expedite formulation.
A simple way to think of it is that citrulline is a precursor to arginine. The only function of citrulline is its conversion to arginine. A study comparing the relative efficiency of arginine and citrulline supplementation conducted in mice concluded that citrulline supplementation may increase arginine availability even more than arginine supplementation itself.¹ Outside of wound healing, healthy people take citrulline supplements for a variety of reasons, including improved athletic performance, lowering blood pressure, and alleviating erectile dysfunction.²
Arginine supplementation has some drawbacks. The primary challenge is the loss of arginine during the first-pass metabolism. The first-pass effect, also known as pre-systemic metabolism, refers to the metabolism of drugs or chemicals in the liver or intestine prior to their reaching the systemic circulation.³ Approximately 40% of dietary arginine is lost during this first-pass effect,4 while citrulline undergoes limited degradation. Arginine is largely metabolized by the liver, whereas citrulline is not taken up by the liver and therefore nearly all the citrulline absorbed from the small intestine bypasses the liver and enters the systemic circulation.5
Other reported challenges with chronic arginine supplementation include gastrointestinal problems and diarrhea.6 This effect is dose dependent, with studies varying from 3 g/day to more than 100 g/day. While the daily dose provided by typical wound supplements probably will not provoke any stomach issues, patients often complain that they believe the nutritional supplement affected them. If a patient believes this is true and stops consuming the supplement, the practitioner is back to square one and must find another intervention.
Finally, the controversy regarding use of arginine in hemodynamically unstable patients and critically ill patients persists. While this controversy should no longer exist,7 it is still brought up at every major wound meeting, indicating that it is still an unanswered question in practitioners’ minds. The conversion of citrulline to arginine occurs continuously if citrulline is circulating in the bloodstream.8 This will maintain a steady release of nitric oxide, which may help answer this issue.
Expedite contains ingredients that reflect the most current science to improve patient outcomes, and this includes citrulline.
References
1. Agarwal U, Didelija IC, Yuan Y, Wang X, Marini JC. Supplemental citrulline is more efficient than arginine in increasing systemic arginine availability in mice. J Nutr. 2017;147(4):596-602. doi:10.3945/jn.116.240382
2. L-citrulline. Rx List. Accessed February 19, 2024. https://www.rxlist.com/l-citrulline/supplements.htm
3. Kenyon EM, Hughes MF. Oral exposure and absorption of toxicants. Compr Toxicol. 2010;1:61-74. Accessed February 19, 2024. https://www.sciencedirect.com/science/article/pii/B9780080468846001032
4. Wu G. Intestinal mucosal amino acid catabolism. J Nutr. 1998;128(8):1249-1252. doi:10.1093/jn/128.8.1249
5. Morris SM Jr. Regulation of enzymes of the urea cycle and arginine metabolism. Annu Rev Nutr. 2002;22:87-105. doi:10.1146/annurev.nutr.22.110801.14054
6. Grimble GK. Adverse gastrointestinal effects of arginine and related amino acids. J Nutr. 2007;137(6 suppl 2):1693S-1701S. doi:0.1093/jn/137.6.1693S
7. Rosenthal MD, Rosenthal C, Patel J, Jordan J, Go K, Moore FA. Arginine in the critically ill: can we finally push past the controversy? International Journal of Critical Care and Emergency Medicine. Accessed February 19, 2024. https://clinmedjournals.org/articles/ijccem/international-journal-of-critical-care-and-emergency-medicine-ijccem-2-017.php?jid=ijccem
8. Maric S, Restin T, Muff JL, et al. Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use. Nutrients. 2021;13(8):2794. Published 2021 Aug 15. doi:10.3390/nu13082794
