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29.07.2015


Adding 200 mg glutathione makes L-citrulline a more effective NO booster

L-Citrulline-based NO boosters can be made more effective by adding glutathione, report researchers at Baylor University in the Journal of the International Society of Sports Nutrition. It's not clear from the study exactly how L-citrulline and glutathione reinforce each other's effect, but the researchers demonstrated this in humans.

L-citrulline and glutathione
L-Citrulline


Glutathione
On entering the body citrulline [top structural formula shown on the right] is converted first of all into L-arginine, an amino acid that functions as a precursor of nitrogen monoxide, or NO. NO in turn activates the enzyme cGMP in the blood vessels. CGMP makes blood vessels wider and suppler. This is why supplementation with citrulline or other NO precursors is interesting for athletes: it boosts the supply of nutrients and oxygen to the muscles. NO also plays a role in the development of stem cells into muscle cells.

There are indications that glutathione [lower structural formula shown above], a protein that cells use for detoxification processes, can boost the effect of L-citrulline. The enzymes that separate NO from arginine work better the more glutathione there is present in the cells. [Amino Acids. 1996 Sep;10(3):277-81] [Am J Physiol. 1993 Sep;265(3 Pt 1):C728-32.]

Study
The researchers did experiments with 4 groups of 15 male students. All of the students did regular weight training.

One group was given a placebo every day for a week [PLC]. A second group took a daily 2 g L-citrulline [CIT], and a third group took a daily 1 g glutathione [GSH]. And finally, a fourth group took a daily 2 g L-citrulline plus 200 mg glutathione [CIT+GSH].

On the last day of the experiment the subjects were given the last dose of their particular supplement, and they had to train their biceps for 60 minutes. The researchers analysed the students' blood just before they took the supplement [Baseline], just before they started training [Pre-EX], just after the training [Post-EX] and 30 minutes after the training session ended [30 Post-EX].

Results
The combination of L-citrulline and glutathione resulted in a higher concentration of NO and higher cGMP activity for 30 minutes after the workout.


Adding 200 mg glutathione makes L-citrulline a more effective NO booster


Adding 200 mg glutathione makes L-citrulline a more effective NO booster


Part of the mechanism responsible for the synergy between citrulline and glutathione is that glutathione probably speeds up the release of NO from arginine. At least, the figure below suggests this.


Adding 200 mg glutathione makes L-citrulline a more effective NO booster


Adding 200 mg glutathione makes L-citrulline a more effective NO booster


Moreover, the combination of L-citrulline and glutathione boosted the concentration of nitrite in the subjects after they'd done the workout. Nitrite is also a precursor of NO. How exactly the combination of L-citrulline and glutathione results in more nitrite being activated the researchers are not sure.

Conclusion
"Our present data suggest that the oral supplementation of L-citrulline combined with glutathione provides an augmenting effect on plasma NO", the researchers summarised. "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, glutathione."

The study was funded by the Japanese Kyowa Hakko Bio. Kyowa markets glutathione as Setria. [kyowa-usa.com]

Source:
Journal of the International Society of Sports Nutrition 2015, 12:27 doi:10.1186/s12970-015-0086-7.

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