Pharmacology & Citrulline & Vasodilation Baste on 14 Aug 2007 04:39 am
L-citrulline and the ‘Arginine Paradox’
Source: British Journal of Pharmacology 2007, Epub ahead of print
Article Type: Original Research
Authors: Schwedhelm et al.
Nitric oxide synthases (NOS) metabolize L-arginine (LA; semi-essential amino acid) to nitric oxide (NO) and L-citrulline (LC; non-essential amino acid). Due to its vasoactive activity, NO induces vasodilation of both arterial and venous blood vessels via activation of soluble guanylyl cyclase. Oral LA treatment in humans, however, is hampered by its extensive metabolism; furthermore LA’s efficiency is suggested to be influenced by its competition with the endogenous NOS inhibitor ADMA (asymmetric dimethylarginine), a phenomenon that has also been called the “arginine paradox”. Interestingly, LC, which does not undergo extensive presystemic and systemic elimination, can serve as an LA precursor. Following its uptake into the body, LA is converted to l-argininosuccinate by argininosuccinate synthase and subsequently to l-arginine by argininosuccinate lyase.
In their randomized, double-blind, placebo-controlled, cross-over study (n=20), Schwedhelm et al. assessed the pharmacokinetic and -dynamic properties of oral LC (and LA) intake. Major findings are:
* oral LC administration effectively increases plasma LA levels
* oral LC administration is well tolerated without side effects
* high dose LC treatment (3g) improves the LA:ADMA ratio
* only high dose LC treatment increases urinary nitrate and cGMP, thus indicating a modulation of NO metabolism
However, no significant effect of endothelial-dependant vasodilation (a secondary study goal) was found, possibly due to the good health status of the study subjects. The authors conclude that “our results provide a rationale for larger, prospective clinical studies with longer treatment periods to investigate the effects of oral l-citrulline supplementation on endothelial function in patients with endothelial dysfunction and vascular disease.”
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