Bioavailability and AUC
Conditions
Keywords
Citrulline,Arginine
Brief summary
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.
Interventions
OTHERRemoval from study. In case of adverse event, subject treated for the AE.
The participation of a subject in this study may have been discontinued for any of the following reasons: * the subject wished to withdraw from study participation; * if, in the opinion of the Investigator, it was in the best interest of the subject; * suspected adverse effects from the test article; * inter-current illness; * violation of the prohibitions and restrictions; * development of an exclusion criteria. Subjects were free to withdraw at any time and need not give a reason, however, every reasonable attempt was made to ascertain such reasons. The data for those subjects who were withdrawn was included in the final clinical report but may be excluded from final data analysis.
OTHERremoval from study
The participation of a subject in this study may have been discontinued for any of the following reasons: * the subject wished to withdraw from study participation; * if, in the opinion of the Investigator, it was in the best interest of the subject; * suspected adverse effects from the test article; * inter-current illness; * violation of the prohibitions and restrictions; * development of an exclusion criteria. Subjects were free to withdraw at any time and need not give a reason, however, every reasonable attempt was made to ascertain such reasons. The data for those subjects who were withdrawn was included in the final clinical report but may be excluded from final data analysis.
Sponsors
Princeton Consumer Research
Vireo Systems, Inc.
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy and hydrated male or female ages 18-64; agrees to refrain from citrulline-rich foods; able and willing to fast 12 hours prior to baseline visit; willing to have blood and urine collections as dictated in the protocol; females of child bearing age have some type of birth control.
Exclusion criteria
* female subject is pregnant; allergies or sensitivities to citrulline products; history of losing consciousness during blood collection;past medical history of iron deficiency; history of or current treatment for hypertension, coronary heart disease; or angina pectoris; known kidney function issues or disorders; being treated with ACE inhibitors; cancer diagnosis within 5 years of visit; history of chronic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arginine levels in plasma | 0-180 minutes | Measured blood plasma arginine levels at various time points. |
Countries
United States
Outcome results
None listed