The amino acid L-citrulline – which Kyowa Hakko manufactures in the US in Cape Girardeau, MO using a proprietary fermentation process – is said to play an important role in nitric oxide (NO) metabolism and regulation. L-Citrulline is converted to L-Arginine in the body to support L-Arginine and NO levels. Increased production of NO promotes vascular dilation which improves oxygen and blood circulation throughout the body.
The new study combines the L-citrulline ingredient with Kyowa’s Setria-branded glutathione to boost nitric oxide levels, and protect against the oxidative reaction of NO in both rodents and humans. The researchers also performed an in vitro test with human cells treated with L-citrulline, glutathione, or a combination of both.
Results of the in vitro test indicated that the combination of the two ingredients boosted nitrite levels in cells significantly more than control.
Commenting on the study's findings, Karen Todd, RD, Sr. Director Global Brand Marketing for Kyowa Hakko USA, told us: "We found that glutathione (Setria) enhances NO-increasing effect by L-Citrulline in terms of quantity and gives a long-lasting benefit, and these are the first time these findings have been published.
"Setria has not been used in sports nutrition formulas," she added, "but Setria should be a new generation ingredient for pre-work formulas."
In vivo data
Writing in the Journal of the International Society of Sports Nutrition, the researchers also reported that data from a rat study supported the in vitro findings with plasma NOx levels significantly greater in rodents fed the combination of L-citrulline and GSH compared with those fed the control or L-citrulline only.
The human study involved 60 resistance-trained males with an average age of 22. The men were randomly assigned to receive supplements containing L-citrulline only (2 g/day), glutathione only (1 g/day), a combination of the two (L-citrulline at 2 g/day and glutathione at 200 mg/day), or a placebo for seven days. After the week of supplementation the men then underwent a resistance exercise session.
Results of the human study indicated that men in the combination group had significantly higher nitrite and NOx at 30 min post-exercise, compared with the placebo group.
In addition, a non-significant increase in cyclic guanosine monophosphate (cGMP) synthesis was also observed. “Intracellular cGMP serves as a cellular messenger and plays a role in a variety of biological processes, and in human blood vessels, results in vasodilation,” they explained.
“Our present data suggest that the oral supplementation of L-citrulline combined with reduced glutathione provides an augmenting effect on plasma NOx. Based on results from recent studies, this may be explained based on the premise that in some cell types, the activity of NO is influenced by the endogenous antioxidant, reduced glutathione.
“Therefore, reduced glutathione may play an important role in protection against oxidative reaction of NO, thus contributing to the sustained release of NO,” they concluded.
Kyowa's Todd added that the study shows that Setria may play an important role in extending the life span for NO, probably due to protection against reactive oxygen species (ROS), and this is important because there are currently no products that extend the life span for NO.
"The combination of L-Citrulline plus Setria is very effective strategy for the long lasting benefit of enhancing blood NO levels following the resistance exercise," she said.
Source: Journal of the International Society of Sports Nutrition
2015, 12:27 doi:10.1186/s12970-015-0086-7
“Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis”
Authors: S. McKinley-Barnard, T. Andre, M. Morita, D.S. Willoughby