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Cited by 80Nitric Oxide and Endothelin EffectsVitamin C and Antioxidants ResearchAntioxidant Activity and Oxidative Stress

Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin-dependent manner? In vitro, in vivo and clinical studies

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Mortensen, Alan, Lykkesfeldt, Jens·2014·Nitric Oxide
DOI 10.1016/j.niox.2013.12.001
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Abstract

Ascorbate (Asc) has been shown to increase nitric oxide (NO) bioavailability and thereby improve endothelial function in patients showing signs of endothelial dysfunction. Tetrahydrobiopterin (BH₄) is a co-factor of endothelial nitric oxide synthase (eNOS) which may easily become oxidized to the inactive form dihydrobiopterin (BH₂). Asc may increase NO bioavailability by a number of mechanisms involving BH₄ and eNOS. Asc increases BH₄ bioavailability by either reducing oxidized BH₄ or preventing BH₄ from becoming oxidized in the first place. Asc could also increase NO bioavailability in a BH₄-independent manner by increasing eNOS activity by changing its phosphorylation and S-nitrosylation status or by upregulating eNOS expression. In this review, we discuss the putative mechanisms by which Asc may increase NO bioavailability through its interactions with BH₄ and eNOS.

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Crossref · 10.1016/j.niox.2013.12.001

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  • Higher intake/plasma levels of vitamin C are associated with higher levels of tetrahydrobiopterin (BH4).

    “There are verifications that higher intake/plasma levels of vitamin C are associated with higher levels of tetrahydrobiopterin [158].”

    From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [158]

  • Resuscitation of burn victims with high-dose ascorbic acid (66 mg/kg/hour for 24 h) was reported to reduce fluid intakes.

    “Resuscitation of burn victims with highdose ascorbic acid (66 mg/kg/hour for 24 h) was reported in 2000 (296) and later (297, 298) to reduce fluid intakes.”

    From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [297]

    The Clinical studies section discusses ascorbate and tetrahydrobiopterin in people with hypertension and in smokers, but not burn resuscitation. Searches for burn victims, 66 mg/kg/hour, and reduced fluid requirements found no passage addressing the reported treatment or outcome in our copy. (LLM, conf=0.76)

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  • Low serum selenium is associated with intense inflammation, organ failures and poor outcome in children and adults.

    “Selenium: Low serum Se is associated with intense inflammation, organ failures and poor outcome in children and adults (290).”

    From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [290]

    The Clinical studies passage discusses vitamin C supplementation and cardiovascular outcomes, not selenium status. Searches for selenium and for low serum selenium with inflammation, organ failure, or poor outcomes found no passage addressing the claim in adults or children. The cited paper therefore does not verify this attribution. (LLM, conf=0.78)

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Authors
Mortensen, A., & Lykkesfeldt, J.
Affiliations
University of Copenhagen (DK)
Corresponding author
Lykkesfeldt, Jens
ORCID
Lykkesfeldt, Jens
Venue
Nitric Oxide
Publisher
Elsevier BV
Published
2014-01
Volume
36
Pages
51-57
ISSN
1089-8603 (ISSN-L)
DOI
10.1016/j.niox.2013.12.001
OpenAlex
W1990623018
Cited by
80
References
61
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 9 · 2022: 6 · 2021: 9 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 3
FWCI
0.51
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Nitric Oxide (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
vitamin C, nitric oxide bioavailability, tetrahydrobiopterin, dihydrobiopterin, endothelial nitric oxide synthase, S-nitrosylation, eNOS phosphorylation, endothelial dysfunction, endothelial function
MeSH terms
Animals, Ascorbic Acid, Biopterins, Cardiovascular Diseases, Guinea Pigs, Humans, Nitric Oxide, Nitrogen, Oxygen, Phosphorylation, Risk, Vasodilation, Biomarkers, Reactive Oxygen Species, Mice, Rats, Nitric Oxide Synthase Type III

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