Role of Vitamin C in the Function of the Vascular Endothelium
Open accessAbstract
SIGNIFICANCE: Vitamin C, or ascorbic acid, has long been known to participate in several important functions in the vascular bed in support of endothelial cells. These functions include increasing the synthesis and deposition of type IV collagen in the basement membrane, stimulating endothelial proliferation, inhibiting apoptosis, scavenging radical species, and sparing endothelial cell-derived nitric oxide to help modulate blood flow. Although ascorbate may not be able to reverse inflammatory vascular diseases such as atherosclerosis, it may well play a role in preventing the endothelial dysfunction that is the earliest sign of many such diseases. RECENT ADVANCES: Beyond simply preventing scurvy, evidence is mounting that ascorbate is required for optimal function of many dioxygenase enzymes in addition to those involved in collagen synthesis. Several of these enzymes regulate the transcription of proteins involved in endothelial function, proliferation, and survival, including hypoxia-inducible factor-1α and histone and DNA demethylases. More recently, ascorbate has been found to acutely tighten the endothelial permeability barrier and, thus, may modulate access of ascorbate and other molecules into tissues and organs. CRITICAL ISSUES: The issue of the optimal cellular content of ascorbate remains unresolved, but it appears that low millimolar ascorbate concentrations are normal in most animal tissues, in human leukocytes, and probably in the endothelium. Although there may be little benefit of increasing near maximal cellular ascorbate concentrations in normal people, many diseases and conditions have either systemic or localized cellular ascorbate deficiency as a cause for endothelial dysfunction, including early atherosclerosis, sepsis, smoking, and diabetes. FUTURE DIRECTIONS: A key focus for future studies of ascorbate and the vascular endothelium will likely be to determine the mechanisms and clinical relevance of ascorbate effects on endothelial function, permeability, and survival in diseases that cause endothelial dysfunction.
Integrity signals
Registry
Cites
Statistics
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?
Glutathione is about twice more active in scavenging peroxynitrite than ascorbate.
“Contrarily, glutathione is about twice more active in scavenging peroxynitrite than ascorbate [68].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [68]
Most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations and compared to other vitamins.
“Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [68]
Dehydroascorbic acid has a half-life of about 6 minutes and is decomposed to 2,3-diketo-1-gulonic acid, losing vitamin C activity.
“It has a half-life of about 6 minutes. It is decomposed to 2,3-diketo-1-gulonic acid (Figure 4) and, in this way, it loses its activity of vitamin C [6,68,73].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [68]
The pKa of ascorbic acid is 4.1-4.2, so it is present completely as a monoanion-ascorbate-at physiological pH.
“The pKa of ascorbic acid is 4.1–4.2. Hence, it is present completely as a monoanion—ascorbate at the physiological pH [1,2,4,68].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [68]
Vitamin C reaches a concentration between 0.5-5 mM in most cells, except erythrocytes, which do not express SVCT2 and have cytosolic levels reflecting plasma levels of about 50 μM.
“Vitamin C reaches a concentration between 0.5–5 mM in most cells with the exception of erythrocytes, which do not express SVCT2, and, hence, their cytosolic levels reflect plasma levels and are about 50 µM [52,55,68,71].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [68]
Vitamin C stimulates collagen synthesis.
“Vitamin C acts as a co-factor for the proline and lysine hydroxylases that stabilise the collagen molecule tertiary structure, and it also promotes collagen gene expression [69,70,71,72,73,74,75,76,77].”
From The Roles of Vitamin C in Skin Health. (2017) · cites this paper as [72]
Vitamin C promotes collagen gene expression.
“Vitamin C acts as a co-factor for the proline and lysine hydroxylases that stabilise the collagen molecule tertiary structure, and it also promotes collagen gene expression [69,70,71,72,73,74,75,76,77].”
From The Roles of Vitamin C in Skin Health. (2017) · cites this paper as [72]
Vitamin C acts as a co-factor for the proline and lysine hydroxylases that stabilise the collagen molecule tertiary structure.
“Vitamin C acts as a co-factor for the proline and lysine hydroxylases that stabilise the collagen molecule tertiary structure, and it also promotes collagen gene expression [69,70,71,72,73,74,75,76,77].”
From The Roles of Vitamin C in Skin Health. (2017) · cites this paper as [72]
Vitamin C is an essential cofactor for endogenous production of norepinephrine, epinephrine, and vasopressin.
“Vitamin C also is an essential cofactor for endogenous production of norepinephrine, epinephrine, and vasopressin [79].”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [79]
The citation lists haven’t been fetched yet
References 187 · Cited by 358
- Authors
- May, J. M., & Harrison, F. E.
- Affiliations
- Vanderbilt University (US)
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2013-12
- Volume
- 19
- Issue
- 17
- Pages
- 2068-2083
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC3869438
- OpenAlex
- W1969375160
- Cited by
- 358
- References
- 187
- Citations by year
- 2026: 23 · 2025: 23 · 2024: 27 · 2023: 42 · 2022: 45 · 2021: 52 · 2020: 40 · 2019: 27 · 2018: 19 · 2017: 21 · 2016: 8 · 2015: 15 · 2014: 13 · 2013: 1
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG038739)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK050435, DK-50435)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- vitamin C, vascular endothelium, endothelial dysfunction, basement membrane, endothelial cell proliferation, apoptosis, nitric oxide, hypoxia-inducible factor-1α, histone demethylase, DNA demethylase, atherosclerosis, sepsis, smoking, diabetes mellitus, ascorbate deficiency
- MeSH terms
- Animals, Antioxidants, Ascorbic Acid, Biological Transport, Capillary Permeability, Endothelium, Vascular, Humans, Phosphorylation, Protein Processing, Post-Translational, Apoptosis, Endothelial Cells, Cell Proliferation
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
