Date of Graduation


Document Type


Degree Name

Bachelor of Science

Degree Level



Health, Human Performance and Recreation


Gray, Michelle

Committee Member/Reader

Ganio, Matthew

Committee Member/Second Reader

Washington, Tyrone




Clinicians, professional athletes, and recreational athletes are interested in supplementation that up-regulates nitric oxide (NO) production in blood vessel endothelium, increasing arterial vasodilation. Benefits from these supplements include improvements in blood pressure, muscle hyperemia, and exercise performance. Citrulline Malate (CM) is a pre-workout ingredient, popular for its ability to increase exercise performance and blood serum concentrations of L-arginine, resulting in NO production. Recently, Inositol-Stabilized Arginine Silicate (ASI, Nitrosigine) has been added to many of the most popular pre-workout blends, following a group of studies showing ASI increases serum arginine and reduces post-workout muscle damage. Research has yet to compare CM and ASI in-vivo using a flow-mediated dilation (FMD) technique, a validated measure of the vascular endothelium’s NO producing ability. Thus, the purpose of this experiment was to determine the effectiveness of ASI, compared to CM and placebo, in up-regulating NO production in blood vessels as measured by acute changes in vasodilation.


Healthy, normotensive, and at least moderately active male (n = 16) and female (n = 8) young adults were recruited to participate. All participants reported no pre-workout supplementation within two weeks of their study participation, and all participants abstained from nicotine, caffeine, and alcohol during their participation.


We utilized a double-blind, within-subjects design where participants reported for three trials, each preceded by a 7-day washout period. Upon reporting to the research center, participants read and signed the informed consent document, gave a brief medical history, and remained in an upright-seated position until their blood pressure and heart rate normalized. The participant then reclined into a comfortable supine position in a phlebotomy chair, and his or her arm was abducted at 70 to 90 degrees and at heart level, depending on the participant’s level of comfort. A baseline FMD measurement was obtained followed by consumption of one clinical dose CM (8g), ASI (1.5g), or dextrose placebo (8g); the supplementation order was randomized controlling for potential order effects. Participants completed a brief 24-hour nutrition survey and waited for 60 minutes. After the waiting period, FMD was repeated. We used screen capture software to record the entire FMD procedure and conducted analyses on the videos using Quipu Cardiac Suite software.


Repeated measures analysis of variance yielded a significant supplement x time effect (p < .001), such that CM and ASI yielded a greater change in FMD response than placebo. After allometric scaling of the FMD values, supplement x time effect remained significant (p = .001).


Both CM and ASI increased vascular NO production as measured by a change in FMD and may be particularly beneficial to individuals looking to increase the potential for muscle hyperemia during exercise. Our results support previous findings that CM and ASI increase blood serum concentrations of arginine, and are effective at increasing vascular endothelium nitric oxide producing capacity.


Citrulline, Malate, Arginine, Vasodilation, Flow-mediated dilation, Ultrasound