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Cited by 299Vitamin C and Antioxidants ResearchAntioxidant Activity and Oxidative StressNitric Oxide and Endothelin Effects

Vitamin C revisited

Open access
Oudemans-van Straaten, Heleen M, Man, Angelique ME Spoelstra-de, de Waard, Monique C·2014·Critical Care
DOI 10.1186/s13054-014-0460-xPMC PMC4423646
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Abstract

This narrative review summarizes the role of vitamin C in mitigating oxidative injury-induced microcirculatory impairment and associated organ failure in ischemia/reperfusion or sepsis. Preclinical studies show that high-dose vitamin C can prevent or restore microcirculatory flow impairment by inhibiting activation of nicotinamide adenine dinucleotide phosphate-oxidase and inducible nitric oxide synthase, augmenting tetrahydrobiopterin, preventing uncoupling of oxidative phosphorylation, and decreasing the formation of superoxide and peroxynitrite, and by directly scavenging superoxide. Vitamin C can additionally restore vascular responsiveness to vasoconstrictors, preserve endothelial barrier by maintaining cyclic guanylate phosphatase and occludin phosphorylation and preventing apoptosis. Finally, high-dose vitamin C can augment antibacterial defense. These protective effects against overwhelming oxidative stress due to ischemia/reperfusion, sepsis or burn seems to mitigate organ injury and dysfunction, and promote recovery after cardiac revascularization and in critically ill patients, in the latter partially in combination with other antioxidants. Of note, several questions remain to be solved, including optimal dose, timing and combination of vitamin C with other antioxidants. The combination obviously offers a synergistic effect and seems reasonable during sustained critical illness. High-dose vitamin C, however, provides a cheap, strong and multifaceted antioxidant, especially robust for resuscitation of the circulation. Vitamin C given as early as possible after the injurious event, or before if feasible, seems most effective. The latter could be considered at the start of cardiac surgery, organ transplant or major gastrointestinal surgery. Preoperative supplementation should consider the inhibiting effect of vitamin C on ischemic preconditioning. In critically ill patients, future research should focus on the use of short-term high-dose intravenous vitamin C as a resuscitation drug, to intervene as early as possible in the oxidant cascade in order to optimize macrocirculation and microcirculation and limit cellular injury.

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  • Continuous renal replacement therapy for more than two weeks is a new cause of acute micronutrient deficiencies and particularly severe copper deficiency that may explain life-threatening complications in patients requiring this therapy.

    “Continuous renal replacement therapy for more than two weeks is a new cause of acute micronutrient deficiencies and particularly of severe copper deficiency that may explain life-threatening complications in patients requiring this therapy (279).”

    From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [279]

    The ‘Critically ill patients’ section discusses vitamin C and other micronutrients as treatments, while ‘Plasma concentrations’ discusses low vitamin C levels during critical illness. Neither passage addresses continuous renal replacement therapy lasting more than two weeks, copper deficiency, or complications caused by that deficiency; searches for those terms found no supporting passage in our copy. (LLM, conf=0.76)

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Research works printed but not linked: 1

  1. [4]van den Berg BM Nieuwdorp M Stroes ES Vink H Glycocalyx and endothelial (dys)function: from mice to men Pharmacol Rep 2006 58 75 80 17332675

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Related

Authors
Oudemans-van Straaten, H. M., Man, A. M. S.-D., & de Waard, M. C.
Venue
Critical Care
Publisher
Springer Science and Business Media LLC
Published
2014-08-06
Volume
18
Issue
4
Pages
460-460
ISSN
1364-8535 (ISSN-L)
DOI
10.1186/s13054-014-0460-x
PMC
PMC4423646
OpenAlex
W2039131669
Cited by
299
References
109
Citations by year
2026: 12 · 2025: 25 · 2024: 19 · 2023: 37 · 2022: 26 · 2021: 38 · 2020: 34 · 2019: 30 · 2018: 31 · 2017: 15 · 2016: 15 · 2015: 15 · 2014: 2
FWCI
1.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Critical Care (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
vitamin C, high-dose intravenous vitamin C, oxidative stress, ischemia-reperfusion injury, sepsis, microcirculatory dysfunction, NADPH oxidase, inducible nitric oxide synthase, tetrahydrobiopterin, superoxide radical scavenging, peroxynitrite, endothelial barrier, occludin, apoptosis, antibacterial defense, antioxidants, cardiopulmonary resuscitation, organ failure, critically ill patients, ischemic preconditioning
MeSH terms
Animals, Antioxidants, Ascorbic Acid, Capillary Permeability, Critical Care, Endothelium, Vascular, Heart, Humans, Microcirculation, Multiple Organ Failure, Vitamins, Reperfusion Injury, Reactive Oxygen Species, Oxidative Stress, Sepsis

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