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

McKinley-Barnard S, Andre T, Morita M, Willoughby DS

Journal of the International Society of Sports Nutrition10 Jun 2015Cited by 29 (Europe PMC)

PMID26097441PMCIDPMC4472409DOI10.1186/s12970-015-0086-7PepBankPUB-26097441

Summary

BackgroundNitric 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.MethodsIn 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.ResultsIn 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).ConclusionsCombining L-citrulline with GSH augments increases in nitrite and NOx levels during in vitro and in vivo conditions.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

1 result from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In rats, adding GSH to L-citrulline increased plasma NOx versus L-citrulline alone.
In plain wordsIn rats, adding GSH increased plasma NOx compared with L-citrulline alone.
Peptide
Glutathione
Outcome
IncreasePlasma NOx versus L-citrulline
Study
ratsn: not reported in source
Sprague-Dawley rats
Comparator
L-citrulline alone
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
50 mg/kg/day · oral gavage · 3 daysAs given in this study (rats).
Source sentences
Summary
In phase two, plasma NOx with L-citrulline + GSH was significantly greater than control and L-citrulline (p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-2609744103

Studies that did not test the peptide alone4

In this study, Glutathione was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Glutathione.

02HumanNot a test of Glutathione aloneRandomized controlled trialMechanism
In resistance-trained males, L-citrulline plus GSH increased nitrite at 30 min post-exercise versus placebo.
In plain wordsIn resistance-trained males, L-citrulline plus GSH increased nitrite after exercise compared with placebo.
Peptide
Glutathione
Outcome
IncreaseNitrite after exercise
Study
n: not reported in source
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Cardiovascular
Measurements
P value for plasma nitrite
< 0.05 p value
L-citrulline plus GSH versus placebo, 30 min post-exercise
Source sentences
Summary
However, nitrite and NOx for L-citrulline + GSH were significantly greater at 30 min post-exercise when compared to placebo (p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Glutathione was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Glutathione.
Show in the study text Report a problemFND-2609744104
03HumanNot a test of Glutathione aloneRandomized controlled trialMechanism
In resistance-trained males, L-citrulline plus GSH increased NOx at 30 min post-exercise versus placebo.
In plain wordsIn resistance-trained males, L-citrulline plus GSH increased NOx after exercise compared with placebo.
Peptide
Glutathione
Outcome
IncreaseNOx after exercise
Study
n: not reported in source
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Cardiovascular
Measurements
P value for plasma NOx
< 0.05 p value
L-citrulline plus GSH versus placebo, 30 min post-exercise
Source sentences
Summary
However, nitrite and NOx for L-citrulline + GSH were significantly greater at 30 min post-exercise when compared to placebo (p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Glutathione was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Glutathione.
Show in the study text Report a problemFND-2609744105
04AnimalNot a test of Glutathione aloneAnimal study (in vivo)Mechanism
In rats, combined L-citrulline and GSH increased plasma NOx versus control.
In plain wordsIn rats, combined L-citrulline and GSH increased plasma NOx compared with control.
Peptide
Glutathione
Outcome
IncreasePlasma NOx versus control
Study
ratsn: not reported in source
Sprague-Dawley rats
Comparator
Purified water control
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
In phase two, plasma NOx with L-citrulline + GSH was significantly greater than control and L-citrulline (p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Glutathione was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Glutathione.
Show in the study text Report a problemFND-2609744102
05LabNot a test of Glutathione aloneIn vitro (cells)Mechanism
In HUVECs, combined L-citrulline and GSH increased nitrite versus control.
In plain wordsIn cells, combined L-citrulline and GSH increased nitrite compared with control.
Peptide
Glutathione
Outcome
IncreaseCell nitrite
Study
humann: not reported in source
HUVECs
Comparator
Control
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
In phase one, nitrite levels in cells treated with L-citrulline and GSH were significantly greater than control (p < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
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 this study, Glutathione was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Glutathione.
Show in the study text Report a problemFND-2609744101

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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