L-Citrulline/L-Arginine Combination May Improve Circulation: Animal Study


The combination of the two amino acids may improve acute nitric oxide bioavailability more than either would by itself.

The combination of amino acids L-citrulline and L-arginine have been shown to have anti-atherosclerotic effects in previous research, but a new animal study suggests the combination may also rapidly increase nitric oxide (NO) bioavailability after short-term supplementation.

NO plays a key role in increasing the body’s blood circulation, and a reduction of NO bioavailability can be associated with atherosclerotic coronary artery disease, say the researchers. L-citrulline and L-arginine have been studied individually in the past for possible benefits to cardiovascular health, but this study is the first time the two have been studied in combination for benefits to acute NO bioavailability, according to Karen Todd, RD, senior director of global brand marketing, Kyowa Hakko U.S.A. Inc. (New York City).

Researchers in Japan studied rats and New Zealand white rabbits that were treated orally with L-citrulline, L-arginine, or a combination of each at half dosage. The animals were given a single 2.85 mmol/kg oral gavage after a 16-hour fast, followed by blood samples collected at 0, 0.5, 1, 2, and 4 hours after the administration. The researchers studied plasma levels of L-arginine, NObioavailability (nitrite plus nitrate), and cGMP (cyclic guanosine monophosphate) concentrations in the blood.

The results showed that the combination of L-citrulline and L-arginine “effectively and rapidly increases plasma L-arginine and aguments NO-dependent responses, particularly within one hour after supplementation,” said the researchers. The combination caused a more pronounced improvement in NO bioavailability that did either of the individual amino acids alone.

“Our data shows for the first time that a combination of oral L-citrulline and L-arginine effectively and rapidly augments NO-dependent response at the acute stage,” the researchers wrote. “This approach may have clinical utility for the regulation of cardiovascular function in humans.”


Morita M et al. “Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability.” Biochemical and Biophysical Research Communications, vol. 454, no. 1 (November 2014: 53-57.


Read more:

L-Citrulline May Improve Circulation More than L-Arginine Can Alone: Rat Study


Michael Crane
Associate Editor
Nutritional Outlook magazine


Photo © iStockphoto.com/spanteldotru

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