Cited by 127Cardiovascular Health and Disease PreventionNitric Oxide and Endothelin EffectsMuscle metabolism and nutrition

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Short-term effects of l-citrulline supplementation on arterial stiffness in middle-aged men

Ochiai, Masayuki, Hayashi, Toshio, Morita, Masahiko, Ina, Koichiro, Maeda, Morihiko, Watanabe, Fumiko, Morishita, Koji·2012·International Journal of Cardiology

DOI 10.1016/j.ijcard.2010.10.004

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Abstract

Background Nitric oxide (NO) plays a key role in the maintenance of vascular tone, contributing to the functional regulation of arterial stiffness. Although oral L-citrulline could become the effective precursor of L-arginine (substrate for endothelial NO synthase) via the L-citrulline/ L-arginine pathway, little is known about the efficacy of L-citrulline application on arterial stiffness.Objective We examined the short-term effects of L-citrulline supplementation on arterial stiffness in humans.Methods In a double-blind, randomized, placebo-controlled parallel-group trial, 15 healthy male subjects (age: 58.3 ± 4.4 years) with brachial-ankle pulse wave velocity (baPWV; index of arterial stiffness >1400 cm/sec) were given 5.6g/day of L-citrulline (n=8) or placebo (n=7) for 7 days. baPWV and various clinical parameters were measured before (baseline) and after oral supplementation of L-citrulline or placebo.Results Compared with the placebo group, baPWV was significantly reduced in the L-citrulline group (p<0.01). No significant differences in blood pressure (BP) were found between the two groups, and no correlation was observed between BP and baPWV. The serum nitrogen oxide (NOx, the sum of nitrite plus nitrate) and NO metabolic products were significantly increased only in the L-citrulline group (p<0.05). Plasma citrulline, arginine and the ratio of arginine/asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase (arginine/ADMA ratio) were significantly increased in the L-citrulline group compared with the placebo group (p<0.05, p<0.01, p<0.05, respectively). Moreover, there was a correlation between the increase of plasma arginine and the reduction of baPWV (r=-0.553, p<0.05).Conclusion These findings suggest that short-term L-citrulline supplementation may functionally improve arterial stiffness, independent of blood pressure, in humans.

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Authors: Ochiai, M., Hayashi, T., Morita, M., Ina, K., Maeda, M., Watanabe, F., & Morishita, K.
Affiliations: Nagoya University (JP)
Corresponding author: Hayashi, Toshio
ORCID: Hayashi, Toshio
Morita, Masahiko
Venue: International Journal of Cardiology
Publisher: Elsevier BV
Published: 2012-03
Volume: 155
Issue: 2
Pages: 257-261
ISSN: 0167-5273 (ISSN-L)
DOI: 10.1016/j.ijcard.2010.10.004
OpenAlex: W2052898997
Cited by: 127
References: 29
Citations by year: 2026: 9 · 2025: 9 · 2024: 3 · 2023: 11 · 2022: 12 · 2021: 10 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 10 · 2016: 12 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 6
FWCI: 2.85
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: International Journal of Cardiology (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science (21590762, 20406004)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Keywords: L-citrulline supplementation, arterial stiffness, brachial-ankle pulse wave velocity, nitric oxide, L-arginine, asymmetric dimethylarginine, endothelial nitric oxide synthase, middle-aged men, blood pressure
MeSH terms: Arginine, Blood Pressure, Citrulline, Humans, Male, Middle Aged, Nitric Oxide, Placebos, Pulsatile Flow, Nitric Oxide Synthase Type III, Ankle Brachial Index, Vascular Stiffness

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Short-term effects of l-citrulline supplementation on arterial stiffness in middle-aged men

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