Cited by 67Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionCardiovascular and exercise physiology

Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure

Open access
Kim, Il-Young, Schutzler, Scott E., Schrader, Amy, Spencer, Horace J., Azhar, Gohar, Deutz, Nicolaas E. P., Wolfe, Robert R.·2015·American Journal of Physiology-Endocrinology and Metabolism

Abstract

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.

Integrity signals

Registry

Crossref · 10.1152/ajpendo.00339.2015

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2015-12-01
Volume
309
Issue
11
Pages
E915-E924
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review