Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure
Open accessAbstract
To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol·kg body wt−1·h−1] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol·kg body wt−1·h−1). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol·kg body wt−1·h−1) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol·kg body wt−1·h−1). Consistent with the kinetic data, RH-FBF in the fasted state was ∼40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.
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In some cases, l-citrulline increased NO synthesis, but no changes in blood pressure were observed.
“In some cases, l-citrulline increased NO synthesis, but no changes in blood pressure were observed (506).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [506]
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Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
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- Authors
- Kim, I.-Y., Schutzler, S. E., Schrader, A., Spencer, H. J., Azhar, G., Deutz, N. E. P., & Wolfe, R. R.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Texas A&M University (US)
- Corresponding author
- Kim, Il-Young
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2015-12-01
- Volume
- 309
- Issue
- 11
- Pages
- E915-E924
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC4669336
- OpenAlex
- W2215738169
- Cited by
- 67
- References
- 45
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 11 · 2021: 15 · 2020: 9 · 2019: 10 · 2018: 5 · 2017: 2 · 2016: 2
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000039, KL2TR000063)
- National Institute on Aging (P30AG028718, PG30-AG-028718)
- National Center for Advancing Translational Sciences
- 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 › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- citrulline supplementation, nitric oxide production, heart failure, aging, vascular dysfunction, reactive hyperemia, forearm blood flow, arginine metabolism, older adults
- MeSH terms
- Adult, Aged, Arginine, Cardiovascular Agents, Citrulline, Endothelium, Vascular, Female, Forearm, Heart Failure, Humans, Hyperemia, Kinetics, Male, Middle Aged, Nitric Oxide, Regional Blood Flow, Severity of Illness Index, Up-Regulation, Dietary Supplements, Young Adult, Elder Nutritional Physiological Phenomena
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