ArticleAmerican journal of physiology. Endocrinology and metabolism2015
Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure.
Article in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis.Nutrients · 2022Pooled it
- Improved vascular function and functional capacity following l-citrulline administration in patients with heart failure with preserved ejection fraction: a single-arm, open-label, prospective pilot study.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Trial
- Trial
- Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women.Nutrients · 2022Trial
- Supplemental Watermelon Juice Attenuates Acute Hyperglycemia-Induced Macro-and Microvascular Dysfunction in Healthy Adults.The Journal of nutrition · 2021Trial
- Acute L-Citrulline Supplementation Increases Nitric Oxide Bioavailability but Not Inspiratory Muscle Oxygenation and Respiratory Performance.Nutrients · 2021Trial
- Daily Consumption of a Specially Formulated Essential Amino Acid-Based Dietary Supplement Improves Physical Performance in Older Adults With Low Physical Functioning.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Trial
- Response of exercise-onset vasodilator kinetics to L-citrulline supplementation during different phases of the menstrual cycle.Physiological reports · 2020Trial
- Inter-Individual Responses to Citrulline Malate Oral Supplementation on Post-Exercise Hypotension in Hypertensives: A 24-Hour Analysis.Arquivos brasileiros de cardiologia · 2019Trial
- Trial
- Impact of l-citrulline supplementation on oxygen uptake kinetics during walking.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2018Trial
- Does l-citrulline supplementation improve exercise blood flow in older adults?Experimental physiology · 2017Trial
- The Janus face of L-arginine supplementation in cardiovascular health and aging exploration of underlying mechanisms.Frontiers in aging · 2026Review
- Acute effect of citrulline malate on flow-mediated dilation and serum pharmacodynamics in healthy young males.Frontiers in physiology · 2026Article
- Declining nitric oxide bioavailability in cardiovascular aging: mechanistic insights and emerging interventions.The journal of cardiovascular aging · 2025Article
- Review
- Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review.Nutrients · 2023Review
- Adherence to the Mediterranean Diet Association with Serum Levels of Nitric Oxide, Prostacyclin, and Thromboxane BNutrients · 2023Article
- Prevention of Loss of Muscle Mass and Function in Older Adults during COVID-19 Lockdown: Potential Role of Dietary Essential Amino Acids.International journal of environmental research and public health · 2022Review
- Watermelon and L-Citrulline in Cardio-Metabolic Health: Review of the Evidence 2000-2020.Current atherosclerosis reports · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.