Say hello to Citrulline
Most people think of arginine when they think about increasing Nitric Oxide (NO) production for improved blood flow. However, I stumbled upon a product that Pure encapsulations sells a product for NO production.
See link below
It contains various agents to enhance NO production. One of them is citrulline. They claim that citrulline can increase plasma arginine to a greater degree than arginine supplementation alone.
I wanted to review these claims further. Citrulline is the endogenous precursor for the synthesis of arginine and has been proposed as an alternative to arginine supplementation. The only known fate of this amino acid is conversion to arginine (Agarwal, Didelija, Yuan, Wang, & Marini, 2017). A journal article published in 2017 confirmed this. Dietary arginine supplementation suffers from various drawbacks, including extensive first-pass extraction. Another issue with arginine supplementation is chronic use may cause GI distress as well as a sudden drop in blood pressure (Agarwal et al., 2017). Given these drawbacks of arginine supplementation, citrulline has been suggested as a potential alternative to increase arginine availability. Citrulline does not undergo first pass metabolism in the gut or liver, and demonstrates to be just as efficient or more efficient than arginine in increasing NO production. Although the study was not perfect, since it was using mice and not humans, it still provided some valuable insight. Interestingly, citrulline supplementation resulted in both an increase in arginine flux as well as in a greater increase in plasma arginine concentration than arginine supplementation itself. For these reasons, citrulline was a more efficient supplement than arginine in increasing arginine availability (Agarwal et al., 2017). “This is due to the fact that the only known fate of citrulline is its conversion into arginine and because citrulline losses in the urine are minimal (even when large citrulline doses are administered as a single bolus)” (Agarwal et al., 2017). This seems to be due to citrulline’s ability to escape first past metabolism. 70% of arginine disappears before reaching peripheral circulation, which limits arginine’s availability. This is likely the reason why supplementation with citrulline can promote a greater response in NO production.
Agarwal, U., Didelija, I. C., Yuan, Y., Wang, X., & Marini, J. C. (2017). Supplemental Citrulline Is More Efficient Than Arginine in Increasing Systemic Arginine Availability in Mice. J Nutr, 147(4), 596-602. doi:10.3945/jn.116.240382