Citrulline dietary supplements are of interest for improving cardiovascular and exercise performance. The health benefits of citrulline are attributable to its ability to increase arginine levels in the body through the intestinal-renal arginine conversion pathway. From a dietary supplementation standpoint, citrulline offers advantages over arginine due to its reduced first-pass metabolism and ready conversion to arginine within the body. While L-citrulline is the most widely used citrulline dietary supplement, additional salt forms such as citrulline maleate and citrulline HCl may provide improvements in the delivery of arginine to the body. The present study compared the single-dose pharmacokinetics of L-citrulline and citrulline HCl formulations in healthy human subjects. A total of 17 subjects were randomly assigned to groups receiving either 6 g of L-citrulline, 6 g of citrulline HCl or 2 g of citrulline HCl. The resulting increases in citrulline and arginine in plasma and urine samples were determined using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM/MS). All citrulline dietary supplements examined produced time-dependent increases in plasma citrulline and arginine. Both maximal plasma concentration (Cmax) and area under the plasma vs time curve (AUC) for citrulline were modestly reduced in the 6 g citrulline HCl treatment group, the resulting arginine Cmax and AUCs were similar for both L-citrulline and citrulline HCl at the 6 g dose. While the 2 g dose of citrulline HCl had reduced Cmax and AUC values compared to 6 g doses, the time to reach peak levels of arginine were significantly shorter. Furthermore, examination of the relative arginine bioavailability achieved with the 6 g and 2 g citrulline HCl compared to the 6 g L-citrulline was approximately 120% and 215%, respectively, consistent with an improved citrulline to arginine conversion efficiency with the citrulline HCl formulations.
Age range
18 Years – 64 Years
Sex
ALL
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Arginine levels in plasma
Timeframe: 0-180 minutes