Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability

Morita, Masahiko; Hayashi, Toshio; Ochiai, Masayuki; Maeda, Morihiko; Yamaguchi, Tomoe; Ina, Koichiro; Kuzuya, Masafumi

doi:10.1016/j.bbrc.2014.10.029

Cited by 140Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionBiochemical effects in animals

Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability

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Morita, Masahiko, Hayashi, Toshio, Ochiai, Masayuki, Maeda, Morihiko, Yamaguchi, Tomoe, Ina, Koichiro, Kuzuya, Masafumi·2014·Biochemical and Biophysical Research Communications

DOI 10.1016/j.bbrc.2014.10.029

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Abstract

BACKGROUND: Chronic supplementation with L-citrulline plus L-arginine has been shown to exhibit anti-atherosclerotic effects. However, the short-term action of this combination on the nitric oxide (NO)-cGMP pathway remains to be elucidated. The objective of the present study was to investigate the acute effects of a combination of oral L-citrulline and L-arginine on plasma L-arginine and NO levels, as well as on blood circulation. METHODS: Rats or New Zealand white rabbits were treated orally with L-citrulline, or L-arginine, or a combination of each at half dosage. Following supplementation, plasma levels of L-arginine, NOx, cGMP and changes in blood circulation were determined sequentially. RESULTS: L-Citrulline plus L-arginine supplementation caused a more rapid increase in plasma L-arginine levels and marked enhancement of NO bioavailability, including plasma cGMP concentrations, than with dosage with the single amino acids. Blood flow in the central ear artery in rabbits was also significantly increased by L-citrulline plus L-arginine administration as compared with the control. CONCLUSION: Our data show for the first time that a combination of oral L-citrulline and L-arginine effectively and rapidly augments NO-dependent responses at the acute stage. This approach may have clinical utility for the regulation of cardiovascular function in humans.

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Citrulline has the potential to increase plasma nitrate and nitric oxide availability.
“Citrulline, the end product of arginine-mediated nitric oxide production, has shown the potential to increase plasma nitrate and NO availability (Schwedhelm et al. 2007; Morita et al. 2014).”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Morita et al. 2014
Citrulline supplementation in human subjects enhanced the bioavailability of nitric oxide.
“enhanced the bioavailability of nitric oxide (Morita et al. 2014)”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Morita et al. 2014

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Authors: Morita, M., Hayashi, T., Ochiai, M., Maeda, M., Yamaguchi, T., Ina, K., & Kuzuya, M.
Affiliations: Nagoya University (JP)
Corresponding author: Hayashi, Toshio
ORCID: Morita, Masahiko
Hayashi, Toshio
Kuzuya, Masafumi
Venue: Biochemical and Biophysical Research Communications
Publisher: Elsevier BV
Published: 2014-11
Volume: 454
Issue: 1
Pages: 53-57
ISSN: 0006-291X (ISSN-L)
DOI: 10.1016/j.bbrc.2014.10.029
OpenAlex: W2058486417
Cited by: 140
References: 36
Citations by year: 2026: 14 · 2025: 8 · 2024: 14 · 2023: 13 · 2022: 16 · 2021: 16 · 2020: 17 · 2019: 17 · 2018: 10 · 2017: 7 · 2016: 6 · 2015: 2
FWCI: 3.32
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-sa/3.0/ (vor)
Locations: Biochemical and Biophysical Research Communications (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: KYOWA HAKKO BIO CO., LTD
Topics: Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Health Sciences › Medicine › Physiology › Biochemical effects in animals
Keywords: citrulline, L-arginine, amino acid supplementation, nitric oxide bioavailability, nitric oxide-cGMP pathway, cyclic GMP, blood flow, ear artery, cardiovascular function, atherosclerosis
MeSH terms: Administration, Oral, Animals, Arginine, Biological Availability, Citrulline, Drug Synergism, Cyclic GMP, Humans, Male, Nitric Oxide, Rabbits, Signal Transduction, Rats, Sprague-Dawley, Dietary Supplements, Atherosclerosis, Rats

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Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability

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