The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Ascorbic Acid Reverses Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease
Abstract
Background In the setting of atherosclerosis, endothelial vasomotor function is abnormal. Increased oxidative stress has been implicated as one potential mechanism for this observation. We therefore hypothesized that an antioxidant, ascorbic acid, would improve endothelium-dependent arterial dilation in patients with coronary artery disease. Methods and Results Brachial artery endothelium-dependent dilation in response to hyperemia was assessed by high-resolution vascular ultrasound before and 2 hours after oral administration of either 2 g ascorbic acid or placebo in a total of 46 patients with documented coronary artery disease. Plasma ascorbic acid concentration increased 2.5-fold 2 hours after treatment (46±8 to 114±11 μmol/L, P =.001). In the prospectively defined group of patients with an abnormal baseline response (<5% dilation), ascorbic acid produced marked improvement in dilation (2.0±0.6% to 9.7±2.0%), whereas placebo had no effect (1.1±1.5% to 1.7±1.5%, P =.003 for ascorbic acid versus placebo). Ascorbic acid had no effect on hyperemic flow or arterial dilation to sublingual nitroglycerin. Conclusions Ascorbic acid reverses endothelial vasomotor dysfunction in the brachial circulation of patients with coronary artery disease. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in patients with atherosclerosis and that endothelial dysfunction may respond to antioxidant therapy.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Hyperglycemic patients experiencing vasodilation have a positive effect following intravenous administration (24 mg/min for 10 min) or oral dose (6 g during 2 days) (Levine et al. 1996).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Levine et al. 1996
Citations
Cites
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9265 · Cited by 5,074
Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis
Celermajer, D. S., Sorensen, K. E., Gooch, V. M., Spiegelhalter, D. J., Miller, O. I., Sullivan, I. D., Lloyd, J. K., & Deanfield, J. E. (1992) · The Lancet · doi:10.1016/0140-6736(92)93147-f · Cited by 4,742
Biochemistry of nitric oxide and its redox-activated forms
Stamler, J. S., Singel, D. J., & Loscalzo, J. (1992) · Science · doi:10.1126/science.1281928 · Cited by 2,744
Role of oxidized low density lipoprotein in atherogenesis.
Witztum, J. L., & Steinberg, D. H. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115499 · Cited by 2,675
Paradoxical Vasoconstriction Induced by Acetylcholine in Atherosclerotic Coronary Arteries
Ludmer, P. L., Selwyn, A. P., Shook, T., Wayne, R. R., Mudge, G. H., Alexander, R. W., & Ganz, P. (1986) · New England Journal of Medicine · doi:10.1056/nejm198610233151702 · Cited by 2,422
Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor
Gryglewski, R. J., Palmer, R. M. J., & Moncada, S. (1986) · Nature · doi:10.1038/320454a0 · Cited by 2,400
Vitamin E Consumption and the Risk of Coronary Heart Disease in Men
Rimm, E. B., Stampfer, M. J., Ascherio, A., Giovannucci, E. L., Colditz, G. A., & Willett, W. C. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282004 · Cited by 2,345
Vitamin E Consumption and the Risk of Coronary Disease in Women
Stampfer, M. J., Hennekens, C. H., Manson, J. E., Colditz, G. A., ROSNER, B. A., & Willett, W. C. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282003 · Cited by 2,085
Ascorbate is an outstanding antioxidant in human blood plasma
Frei, B., England, L., & Ames, B. N. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.16.6377 · Cited by 1,870
Self-citationHypercholesterolemia increases endothelial superoxide anion production.
Ohara, Y., Peterson, T. E., & Harrison, D. G. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116491 · Cited by 1,765
Research works printed but not linked: 6
- 10.1161/res.65.3.2548765 · DOI
- 10.1161/circ.81.2.2105174 · DOI
- 10.1161/circ.90.1.8026037 · DOI
- 10.1161/circ.73.6.3698244 · DOI
- Corretti MC, Plotnick GD, Vogel RA. Technical aspects of evaluating brachial artery endothelium-dependent vasodilatation using high frequency ultrasound. Am J Physiol. 1995;268:H1397-H1404.
- 10.1161/circ.91.5.1525 · DOI
Cited by
Sorted by citations
Items 501–581 of 581
Vitamin C Dosage in Health and Disease
Danboyi, T., Jimoh, A., Hassan-Danboyi, E., & Teru, G. A. D. (2024) · IntechOpen eBooks · doi:10.5772/intechopen.109657 · Cited by 2
Effect of Oral Care on Endothelial Dysfunction in Patients with Acute Coronary Syndrome
Imamura, S., Miyata, M., Ogawa, M., Oketani, N., Hamasaki, S., Hirahara, N., Ninomiya, Y., & Ohishi, M. (2024) · International Heart Journal · doi:10.1536/ihj.23-553 · Cited by 1
Interactions of selenium, vitamin E, and vitamin C in atherosclerosis
May, J. M., & Burk, R. F. (2002) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(02)11036-4 · Cited by 1
Herbal Viagra and nitric oxide: how hard is the evidence?
Cooke, J. P. (2010) · Cureus · doi:10.7759/cureus.13 · Cited by 1
Variação do diâmetro da artéria braquial em crianças obesas: presente e futuro
Costa, K. C. M., Lima, J. C., Nogueira‐de‐Almeida, C. A., Ciampo, L. A. D., & de Souza, C. S. B. (2012) · Revista Paulista de Pediatria · doi:10.1590/s0103-05822012000300019 · Cited by 1
Robinson, A. T., Mazzuco, A., Sabbahi, A., Borghi‐Silva, A., & Phillips, S. A. (2018) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2018-0010 · Cited by 1
Vascular pathophysiology of hypertension
Guzik, T. J., & Touyz, R. M. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780198755777.003.0019 · Cited by 1
Endothelial Vasodilatory Dysfunction and Risk Factors in Adults
Adams, M. R., & Celermajer, D. S. (2007) · Wiley eBooks · doi:10.1002/9780470988473.ch13 · Cited by 1
Vehkavaara, S. (2001) · Työväentutkimus Vuosikirja · Cited by 1
The uremic syndrome and pathophysiology of chronic renal failure
Hörl, W. H. (2004) · Springer eBooks · doi:10.1007/978-1-4020-2275-3_3 · Cited by 1
On, Y. K., Chung, W. Y., Chae, I. H., Kim, C., Sohn, D. W., Oh, B., Lee, M. M., Park, Y. B., & Choi, Y. S. (2001) · Korean Circulation Journal · doi:10.4070/kcj.2001.31.4.411 · Cited by 1
Lack of evidence for vitamin C as acute vasodilator
Madhavan, A., & Goodfellow, J. (2003) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(03)01302-3 · Cited by 1
Kk, S., Sn, S., Bawankule, D., Mishra, S. K., & Raviprakash, V. (2006) · PubMed · Cited by 1
Prehospital thrombolysis: a reappraisal.
Singh, S., & Bahl, V. K. (2004) · PubMed · Cited by 1
The Effects of Exercise on Vascular Physiology in Systemic Sclerosis Patients
Mitropoulos, A. (2018) · Sheffield Hallam University · doi:10.7190/shu-thesis-00213 · Cited by 1
Rationale for Use of Vitamin and Mineral Supplements
Perelson, A., & Ellenbogen, L. (2001) · CRC Press eBooks · doi:10.1201/9781420038392.ch65 · Cited by 1
Forgione, M. A., & Loscalzo, J. (2000) · Developments in cardiovascular medicine · doi:10.1007/978-94-011-4375-2_3 · Cited by 1
A Novel Approach to Treat Peripheral Artery DiseasePreprint
Blum, A. (2023) · Preprints.org · doi:10.20944/preprints202305.0459.v1
Mechanismen und Bedeutung der Endothelfunktion bei koronarer Herzkrankheit
Weidinger, F. F., & Frick, M. (2000) · Journal für Kardiologie (Krause & Pachernegg GmbH)
Prevention of Atherosclerosis: Endothelial Function, Cholesterol, and Antioxidants
Vogel, R. A. (2007) · Springer eBooks · doi:10.1007/978-0-585-38141-1_5
Coronary Artery Disease and Endothelial Function
Schächinger, V., & Zeiher, A. (2002) · Springer eBooks · doi:10.1007/978-3-642-56225-9_55
Metabolic Regulation of Endothelial Dysfunction and Cardiovascular Risk
Young, J. M. (2012) · Otago University Research Archive (University of Otago)
Baudler, S. (2001) · Kölner Universitäts PublikationsServer (Universität zu Köln)
Controversies in Dietary Supplementation
Janson, M. (1997) · Alternative and Complementary Therapies · doi:10.1089/act.1997.3.101
Endothelial Function and Insights for Prevention
Lieberman, E. H., Garces, M. R., & López-Jiménez, F. A. (2001) · Humana Press eBooks · doi:10.1007/978-1-59259-001-8_2
Lipids, inflammation, and the Renin-Angiotensin System
van der Harst, P. (2006)
Targeted delivery of biological agents.
Greig, J. A. (2009) · Enlighten: Theses (The University of Glasgow)
Ascorbic Acid and Atherosclerosis
Ketsawatsakul, U., & Akarasereenont, P. (2000) · Journal of Basic and Applied Pharmacology
Vitamin C and Treating Coronary Artery Disease: More Hype than Hope?
Elboudwarej, O. (2010) · eScholarship (California Digital Library)
The impact of coronary revascularisation on endothelial and platelet function
Amoroso, G. (2001) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Nitrite Ion : Its role in vasoregulation and host defenses
Björne, H. (2005) · Figshare
Hipercolesterolemia y disfunción endotelial: mecanismos implicados
Cachofeiro, V., Vázquez-Pérez, S., Jiménez, N. D. L. H., Cediel, E., Sanz‐Rosa, D., Olivares, E., & Juliá, V. L. (2003) · Hipertensión y Riesgo Vascular · doi:10.1016/s1889-1837(03)71363-4
Las estatinas como antioxidantes
Heras, N. D. L., Sanz‐Rosa, D., Miana, M., Martín, B., Cachofeiro, V., & Lahera, V. (2005) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/s0214-9168(05)73377-5
Antioxidants and Endothelial Function: Human Studies
Binggeli, C., Sudano, I., van der Loo, B., Cosentino, F., Noll, G., & Lüscher, T. F. (2006) · Developments in cardiovascular medicine · doi:10.1007/0-387-29553-4_11
Lee, J. T., Peng, G. S., Hsu, C. H., Cheng, C., Lin, J. C., Hsu, Y. D., Lin, J., & Yin, J. H. (2005)
Nitric Oxide and Peroxynitrite: Effects on Cardiovascular Function
Roche, L. D. (2010)
Arvind, M. N., & Channaraya, V. (2013) · Journal of Evolution of Medical and Dental Sciences · doi:10.14260/jemds/1692
Vitamin C and Cardiovascular Disease: Mechanisms of Action
Frei, B. B. (1998) · Springer eBooks · doi:10.1007/978-88-470-2244-7_7
Self-citationKregel, K. C., & Zhang, H. J. (2012)
Endothelial dysfunction in children with chronic renal failure : causes and therapies
Bennett-Richards, K. (2005) · OpenGrey (Institut de l'Information Scientifique et Technique)
Protection of vascular nitric oxide by superoxide dismutase mimetics
MacKenzie, A. R. (1998) · Enlighten: Theses (The University of Glasgow) · doi:10.5525/gla.thesis.71832
Cellular Redox Activity and Molecular Functions of Ascorbic Acid
Lodge, J. K. (2005) · Oxidative stress and disease · doi:10.1201/9781420028096.ch12
Houston, M. C. (2009) · CRC Press eBooks · doi:10.1201/9781420067637.ch5
Effects of antihypertensive drugs on conduit artery endothelial function
Ghiadoni, L., Virdis, A., Versari, D., Taddei, S., & Salvetti, A. (2004)
Slattery, D. (2014) · QSpace (Queen's University Library)
CENTRAL NEURAL MECHANISMS OF SALT-SENSITIVE HYPERTENSION
Larson, R. A. (2016) · doi:10.37099/mtu.dc.etdr/188
Vitamins, Minerals and Flavonoids Intake and the Risk of Cardiovascular Diseases
Tabatabai, S., & Keshavarz, S. A. (2007) · DOAJ (DOAJ: Directory of Open Access Journals)
Cardiovascular Consequences of Estrogen Deficiency: Studies in Premenopausal Women
O’Donnell, E. (2014) · TSpace (University of Toronto)
Bilehjani, E., Fakhari, S., Bavil, F. M., & Bakhshalizadeh, S. (2019) · Medical Journal of Tabriz University of Medical Sciences and Health Services · doi:10.34172/mj.2019.003
Azuma, A., Miura, H., Ishikawa, M., & Tamura, Y. (2020) · 体力科學 · doi:10.7600/jspfsm.69.229
Simon, B., Noll, B., & Maisch, B. (1999) · Herz
Ascorbic Acid and Endothelial NO Synthesis
a, R. H., & b, E. W. (2003) · AOCS Publishing eBooks · doi:10.1201/9781439822173.ch5
Tomanek, R. J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4887-7_9
McMurtry, M. S., & Michelakis, E. D. (2011) · Springer eBooks · doi:10.1007/978-1-4614-1475-9_11
(2018) · Wiley eBooks · doi:10.1002/9781118829875.refs
Antioxidants and Endothelial Function: Human Studies
Binggeli, C., Sudano, I., Noll, G., & Lüscher, T. F. (2000) · Developments in cardiovascular medicine · doi:10.1007/978-94-011-4375-2_8
(2021) · International Journal of Biology Pharmacy and Allied Sciences · doi:10.31032/ijbpas/2021/10.4.5465
Micronutrients and Cardiovascular Disease
Witte, K. K., & Clark, A. L. (2003) · CRC Press eBooks · doi:10.1201/9780203507629.sec2
Effect of Age and Fitness on Vascular Function and Oxidative Stress During Acute Inflammation
Lefferts, E. C. (2019) · Case Medical Research · doi:10.31525/ct1-nct03889158
Oxidativer Stress und kardiovaskuläre Erkrankungen
Bassenge, E., Daiber, A., & Schneider, H. T. (2006) · Steinkopff eBooks · doi:10.1007/3-7985-1560-3_9
Potential Benefits for the Use of Vitamin and Mineral Supplements
Moreines, J., Cotter, R. L., & Ellenbogen, L. (2007) · CRC Press eBooks · doi:10.1201/9781420008890.ch10
Aceite de oliva: Un medicamento para la salud cardiovascular
Correa, J. A. G. (2019) · UMA Editorial eBooks · doi:10.24310/mumaedmumaed.77
The nitrite reductase activity of xanthine oxidoreductase sustains cardiovascular healthPreprint
Dyson, N., Khambata, R. S., Parakaw, T., Massimo, G., Khuat, N. H., Noor, A. A., Gee, L. C., Lim, I., Siddique, U., Sullivan, A. J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.01.621390
Miric, D. J., Grbić, R., Vasić, A., Božović, B., Dragojević, I. M., Marković, M., & Nestorović, V. (2006) · Praxis medica · doi:10.70949/pramed200602146m
Chandrasiri, N., Mapalagamage, M., Gunasekara, H., Silva, D. D., Premawansa, G., Handunnetti, S. M., & Premawansa, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.19.677322
Block, G., Jensen, C. D., Norkus, E. P., Hudes, M. L., & Crawford, P. B. (2021) · Figshare · doi:10.6084/m9.figshare.15064123
Block, G., Jensen, C. D., Norkus, E. P., Hudes, M. L., & Crawford, P. B. (2021) · Figshare · doi:10.6084/m9.figshare.15064111
Block, G., Jensen, C. D., Norkus, E. P., Hudes, M. L., & Crawford, P. B. (2021) · Figshare · doi:10.6084/m9.figshare.15064117
Touati, S. (2010) · doi:10.70675/c9326786z6325z4f26zbae3ze520f1bdc32f
Tian, P., Su, C., Yang, Y., Su, Z., Gao, M., Tan, X., & 张秋雁 (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1920716
Coronary Atherosclerosis: Chronic Coronary Syndromes
Gould, K. L. (2002) · Springer eBooks · doi:10.1007/978-3-642-56225-9_50
Schär, M. Y. (2014) · UEA Digital Repository (University of East Anglia)
Diet and Nutrition to Prevent and Treat Cardiovascular Diseases
Masuda, H. (2013) · Springer eBooks · doi:10.1007/978-3-7091-1334-9_5
Ascorbic Acid Infusion Attenuates the Pressor Response to Voluntary Apnea in Postmenopausal Women
Patel, H., Randolph, B. J., & Muller, M. D. (2015) · TopSCHOLAR (Western Kentucky University)
Faulks (2000) · doi:10.1002/(sici)1097-0010(20000515)80:7
Andersen (2000) · doi:10.1002/1097-4598(200007)23:7
Metadata
- Authors
- Levine, G. N., Frei, B., Koulouris, S. N., Gerhard, M. D., Keaney, J. F., & Vita, J. A.
- Affiliations
- Boston University (US)
- Venue
- Circulation
- Published
- 1996-03-15
- Volume
- 93
- Issue
- 6
- Pages
- 1107-1113
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2035433779
- Cited by
- 582
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 12 · 2018: 8 · 2017: 12 · 2016: 7 · 2015: 14 · 2014: 6 · 2013: 14 · 2012: 12
- FWCI
- 34.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f32hl008635-01, 7r29hl049954-05, 1r01hl053398-01a1)
- National Heart, Lung, and Blood Institute (HL 53398, HL-08635, HL49954)
- 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 › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- vitamin C, endothelial dysfunction, endothelium-dependent vasodilation, coronary artery disease, oxidative stress, antioxidant therapy, brachial artery, atherosclerosis, hyperemic flow
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antioxidants, Ascorbic Acid, Coronary Circulation, Coronary Disease, Endothelium, Vascular, Female, Humans, Male, Middle Aged, Nitric Oxide, Vasodilation
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