J Int Soc Sports Nutr. 2015; 12: 27.

Published online 2015 Jun 10. doi:  10.1186/s12970-015-0086-7

PMCID: PMC4472409

PMID: 26097441

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

Sarah McKinley-Barnard, Tom Andre, Masahiko Morita, and Darryn S. Willoughby

Sarah McKinley-Barnard

Department of Health, Human Performance, and Recreation, Baylor University, Exercise and Biochemical Nutritional Lab, 76798 Waco, TX USA

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Tom Andre

Department of Health, Human Performance, and Recreation, Baylor University, Exercise and Biochemical Nutritional Lab, 76798 Waco, TX USA

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Masahiko Morita

Function Research Group, Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD., 2, Miyukigaoka, 305-0841 Tsukuba, Ibaraki Japan

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Darryn S. Willoughby

Department of Health, Human Performance, and Recreation, Baylor University, Exercise and Biochemical Nutritional Lab, 76798 Waco, TX USA

Find articles by Darryn S. Willoughby

Department of Health, Human Performance, and Recreation, Baylor University, Exercise and Biochemical Nutritional Lab, 76798 Waco, TX USA

Function Research Group, Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD., 2, Miyukigaoka, 305-0841 Tsukuba, Ibaraki Japan

Sarah McKinley-Barnard, Email: ude.rolyab@yelnikcm_haras.

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Received 2015 Mar 21; Accepted 2015 May 18.

Copyright © McKinley-Barnard et al. 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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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: Nitric oxide, L-citrulline, L-arginine, Glutathione, Resistance exercise