“[O]ur data shows that a combination of oral L-citrulline and L-arginine effectively increases plasma L-arginine levels in humans. This indicates that a combination of L-citrulline and L-arginine might have a more beneficial effect than a single dose of L-arginine alone,” wrote researchers from Kyowa Hakko Bio and Nagoya University Graduate School of Medicine.
Commenting on the study’s findings, Danielle Citrolo, PharmD, Technical Services Manager at Kyowa Hakko USA, told NutraIngredients-USA: “This study supports that this patented combination is an effective means to raise plasma arginine levels, possibly more effective than either alone as previous research has also found. Kyowa has patented this effective combination and is now available as Velox - Patented Performance Blend, exclusively from Kyowa Hakko.”
The importance of arginine
L-arginine is a conditionally essential amino acid, and a precursor to the potent vasodilator nitric oxide (NO), a compound which primarily dilates blood vessels and improves blood flow. The amino acid has been reported to have a variety of effects, including improved endothelial function, enhanced sport performance, improved insulin resistance, and improved erectile function, explained the Japanese authors of the new paper in Bioscience, Biotechnology, and Biochemistry.
“However, relatively large doses of l-arginine are required to produce these effects in humans. Approximately 40% of oral l-arginine is metabolized by arginase on the first pass, and a further 15% of systemic l-arginine is abstracted and metabolized by the liver,” they added.
The amino acid L-citrulline plays also an important role in nitric oxide (NO) metabolism and regulation as a precursor to L-arginine.
Study details
The new study tested a combination of L-arginine and L-citrulline to raise plasma L-arginine levels in 45 healthy Japanese men. The men were assigned to receive 2 grams per day of L-citrulline or 2 grams per day of L-arginine, or a combination of each at half dosage (1.0 g/day) or placebo (cornstarch) in capsule form for eight days.
The data revealed that, after a single dose, the L-arginine levels were significantly higher in the combination group one after ingestion compared to L-citruline only. The level was also higher versus L-arginine but this difference did not reach statistical significance.
Over the eight-day study, significant higher levels of plasma L-arginine levels were observed in the combination group one hour after ingestion, compared with both single amino acids, said the researchers. In addition, the area under the curve, which is a measure of bioavailability, was also significantly higher in the l-arginine and combination groups than in the placebo group.
Commenting on the potential mechanism(s) of action, the researchers note that L-citrulline may suppress the activity of arginase, an enzyme that converts l-arginine to urea and l-ornithine. Another mechanism involves the conversion of L-citrulline to L-arginine, “thus contributing to a sustained l-arginine supply”, they said.
“Taken together, L-citrulline appears to work as an inhibiter of arginase and precursor of L-arginine: as a result, plasma L-arginine synergistically increases when it is simultaneously supplemented with L-arginine.”
Animal data
The study builds on findings from animals published in Biochemical and Biophysical Research Communications (2014, Vol. 45, pp. 53-57). Data from the animal studies indicated that the L-citrulline/L-arginine combination ingredient was effective at boosting plasma L-arginine levels and enhancing nitric oxide bioavailability post supplementation.
Source: Bioscience, Biotechnology, and Biochemistry
2017, Volume 81, Issue 2, doi:
“The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males”
Authors: T. Suzuki et al.