The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Short-term effects of l-citrulline supplementation on arterial stiffness in middle-aged men
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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“In human subjects, citrulline decreased arterial stiffness in middle-aged men (Ochiai et al. 2012).”
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 Ochiai et al. 2012
In the citing paper
“Previous experiments indicate that citrulline supplementation at similar doses to those used for our experiment decreased arterial stiffness in middle-age men (Ochiai et al. 2012)”
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 Ochiai et al. 2012
Citations
Cites
Abnormal Endothelium-Dependent Vascular Relaxation in Patients with Essential Hypertension
Panza, J. A., Quyyumi, A. A., Brush, J. E., & Epstein, S. E. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007053230105 · Cited by 2,366
Ethical authorship and publishing
Coats, A. J. S. (2008) · International Journal of Cardiology · doi:10.1016/j.ijcard.2008.11.048 · Cited by 2,142
Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure
Leone, A., Moncada, S., Vallance, P., Calver, A., & Collier, J. (1992) · The Lancet · doi:10.1016/0140-6736(92)90865-z · Cited by 2,107
Yamashina, A., Tomiyama, H., Takeda, K., Tsuda, H., Arai, T., Hirose, K., Koji, Y., Hori, S., & Yamamoto, Y. (2002) · Hypertension Research · doi:10.1291/hypres.25.359 · Cited by 1,625
Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.
Johnstone, M. T., Creager, S. J., Scales, K. M., Cusco, J. A., Lee, B. K., & Creager, M. A. (1993) · Circulation · doi:10.1161/01.cir.88.6.2510 · Cited by 1,117
Arginase: an emerging key player in the mammalian immune system
Munder, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00291.x · Cited by 725
Schwedhelm, E., Maas, R., Freese, R., Jung, D., Lukacs, Z., Jambrecina, A., Spickler, W., Schulze, F., & Böger, R. H. (2008) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2007.02990.x · Cited by 494
Yamashina, A., Tomiyama, H., Arai, T., Hirose, K., Koji, Y., Hirayama, Y., Yamamoto, Y., & Hori, S. (2003) · Hypertension Research · doi:10.1291/hypres.26.615 · Cited by 488
Hecker, M., Sessa, W. C., Harris, H. J., Änggård, E., & Vane, J. R. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8612 · Cited by 462
Brachial–ankle pulse wave velocity: an index of central arterial stiffness?
Sugawara, J., Hayashi, K., Yokoi, T., Cortez‐Cooper, M. Y., DeVan, A. E., Antón, M. M., & Tanaka, H. (2005) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1001838 · Cited by 454
Research works printed but not linked: 1
- Hecker, 1990, The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: Cultured endothelial cells recycle L-citrulline to L-arginine, Proc Natl Acad Sci USA, 87, 8612, 10.1073/pnas.87.21.8612 · DOI
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Arginine de novo and nitric oxide production in disease states
Luiking, Y. C., Have, G. A. M. T., Wolfe, R. R., & Deutz, N. E. P. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00284.2012 · Cited by 250
l-Citrulline Supplementation: Impact on Cardiometabolic Health
Allerton, T. D., Proctor, D. N., Stephens, J. M., Dugas, T. R., Spielmann, G., & Irving, B. A. (2018) · Nutrients · doi:10.3390/nu10070921 · Cited by 251
Holguín, F., COMHAIR, S. A. A., Hazen, S. L., Powers, R. W., Khatri, S. S., Bleecker, E. R., Busse, W. W., Calhoun, W. J., Castro, M., Fitzpatrick, A. M., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201207-1270oc · Cited by 169
Figueroa, A., Wong, A., Jaime, S. J., & Gonzales, J. U. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000340 · Cited by 147
Citrulline in health and disease. Review on human studies
Papadia, C., Osowska, S., Cynober, L., & Forbes, A. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2017.10.009 · Cited by 143
Metadata
- Authors
- Ochiai, M., Hayashi, T., Morita, M., Ina, K., Maeda, M., Watanabe, F., & Morishita, K.
- Affiliations
- Nagoya University (JP)
- Corresponding author
- Hayashi, Toshio
- Venue
- International Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 155
- Issue
- 2
- Pages
- 257-261
- ISSN
- 0167-5273 (ISSN-L)
- 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
- 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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