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Review
. 2018 Mar 20;22(1):70.
doi: 10.1186/s13054-018-1996-y.

Making sense of early high-dose intravenous vitamin C in ischemia/reperfusion injury

Angelique M E Spoelstra-de Man  1 , Paul W G Elbers  2 , Heleen M Oudemans-van Straaten  2
Affiliations
Review

Making sense of early high-dose intravenous vitamin C in ischemia/reperfusion injury

Angelique M E Spoelstra-de Man et al. Crit Care. .

Abstract

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

Research grant from ZonMW, the Netherlands Health Organization for Health Research and Development, to perform a randomized controlled trial on high dose vitamin C after cardiac arrest. No financial conflicts of interest.

Disclaimer

The caption for Fig 3 should read as follows: Pleiotropic effects of vitamin C. 1. Vitamin C scavenges free radicals from superoxide (O2∙-). 2. Vitamin C inhibits activation of xanthine oxidase and of 3, NADPH oxidase. 4. Vitamin C protects the mitochondria from oxidative stress caused by increased leakage of electrons from the dysfunctional electron transport chain. 5. Vitamin C recovers tetrahydrobiopterin (BH4) from dihydrobiopterin (BH2), restoring endothelial nitric oxide synthase (eNOS) activity and increasing eNO bioavailability. 6. Vitamin C inhibits inducible NOS (iNOS) activation, preventing profuse iNO production and peroxynitrite (ONOO−) generation. 7. Vitamin C scavenges ONOO−, preventing loosening of the tight junctions of the endothelium. 8. Vitamin C recovers α‐tocopherol, which protects against lipid peroxidation.

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Figures

Fig. 1
Fig. 1
Plasma vitamin C concentration on day 3 categorized by subsequent mortality. Vitamin C concentrations are markedly lower in patients dying in the ICU. Dashed line is deficiency plasma concentration in non-ICU patients. From [8] with permission
Fig. 2
Fig. 2
Vitamin C concentration on day 3 versus sequential organ failure assessment (SOFA) score on day 3. Blue line is an ordinary least squares (OLS) regression fit: SOFA = 20.3 − 3.08 * log2 (Vit-C), pcoef < 0.001, R2 = 0.31. From [8] with permission
Fig. 3
Fig. 3
Pleiotropic effects of vitamin C. 1. Vitamin C scavenges free radicals from superoxide (O2∙-). 2. Vitamin C inhibits activation of xanthine oxidase and of 3, NADPH oxidase. 4. Vitamin C protects the mitochondria from oxidative stress caused by increased leakage of electrons from the dysfunctional electron transport chain. 5. Vitamin C recovers tetrahydrobiopterin (BH4) from dihydrobiopterin (BH2), restoring endothelial nitric oxide synthase (eNOS) activity and increasing eNO bioavailability. 6. Vitamin C inhibits inducible NOS (iNOS) activation, preventing profuse iNO production and peroxynitrite (ONOO−) generation. 7. Vitamin C scavenges ONOO−, preventing loosening of the tight junctions of the endothelium. 8. Vitamin C recovers α‐ tocopherol, which protects against lipid peroxidation
Fig. 4
Fig. 4
Ascorbate (Asc) can enter the cerebrospinal fluid (CSF) directly through the choroid plexus via the sodium-dependent vitamin C transporter (SVCT)2. Ascorbate enters the neuron also via SVCT2. This route is a slow, saturable, controlled process. Dehydroascorbate (DHA) is transported directly and fast into the brain via the abundant glucose transporter (GLUT)1 transporters on the endothelial cells of the blood brain-barrier and via the GLUT1 or GLUT3 on the neurons. Inside the neurons, DHA can be reduced back to ascorbate
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