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J Int Soc Sports Nutr. 2015 Jun 10;12:27. doi: 10.1186/s12970-015-0086-7. eCollection 2015.

Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis.

Author information

1
Department of Health, Human Performance, and Recreation, Baylor University, Exercise and Biochemical Nutritional Lab, 76798 Waco, TX USA.
2
Function Research Group, Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD., 2, Miyukigaoka, 305-0841 Tsukuba, Ibaraki Japan.

Abstract

BACKGROUND:

Nitric oxide (NO) is endogenously synthesized from L-arginine and L-citrulline. Due to its effects on nitric oxide synthase (NOS), reduced glutathione (GSH) may protect against the oxidative reduction of NO. The present study determined the effectiveness of L-citrulline and/or GSH on markers indicative of NO synthesis in in vivo conditions with rodents and humans and also in an in vitro condition.

METHODS:

In phase one, human umbilical vein endothelial cells (HUVECs) were treated with either 0.3 mM L-citrulline, 1 mM GSH (Setria®) or a combination of each at 0.3 mM. In phase two, Sprague-Dawley rats (8 weeks old) were randomly assigned to 3 groups and received either purified water, L-citrulline (500 mg/kg/day), or a combination of L-citrulline (500 mg/kg/day) and GSH (50 mg/kg/day) by oral gavage for 3 days. Blood samples were collected and plasma NOx (nitrite + nitrate) assessed. In phase three, resistance-trained males were randomly assigned to orally ingest either cellulose placebo (2.52 g/day), L-citrulline (2 g/day), GSH (1 g/day), or L-citrulline (2 g/day) + GSH (200 mg/day) for 7 days, and then perform a resistance exercise session involving 3 sets of 10-RM involving the elbow flexors. Venous blood was obtained and used to assess plasma cGMP, nitrite, and NOx.

RESULTS:

In phase one, nitrite levels in cells treated with L-citrulline and GSH were significantly greater than control (p < 0.05). In phase two, plasma NOx with L-citrulline + GSH was significantly greater than control and L-citrulline (p < 0.05). In phase three, plasma cGMP was increased, but not significantly (p > 0.05). However, nitrite and NOx for L-citrulline + GSH were significantly greater at 30 min post-exercise when compared to placebo (p < 0.05).

CONCLUSIONS:

Combining L-citrulline with GSH augments increases in nitrite and NOx levels during in vitro and in vivo conditions.

KEYWORDS:

Glutathione; L-arginine; L-citrulline; Nitric oxide; Resistance exercise

PMID:
26097441
PMCID:
PMC4472409
DOI:
10.1186/s12970-015-0086-7
[Indexed for MEDLINE]
Free PMC Article

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