Neuroprotective Properties of Vitamin C: A Scoping Review of Pre-Clinical and Clinical Studies

Kangisser, Lauren; Tan, Elinor; Bellomo, Rinaldo; Deane, Adam M; Plummer, Mark P.

doi:10.1089/neu.2020.7443

Cited by 11 publications

(11 citation statements)

References 63 publications

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“…The role of ascorbic acid during homeostasis is thought to mostly involve its antioxidant, oxygen radical scavenging and enzymatic cofactor properties; therefore, its potential as a neuroprotective agent in neurodegenerative diseases, ischemia, stroke, and traumatic brain injury have been the primary focus of preclinical and clinical investigations [ 21 , 34 ]. The potential importance of a more direct and immediate role of AA as a neuromodulator is often overlooked even though AA has been demonstrated to regulate neurotransmitters, receptors and ion channels [ 12 , 14 , 15 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices

et al. 2022

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Ascorbic acid (AA; a.k.a. vitamin C) is well known for its cellular protection in environments of high oxidative stress. Even though physiological concentrations of AA in the brain are significant (0.2–10 mM), surprisingly little is known concerning the role of AA in synaptic neurotransmission under normal, non-disease state conditions. Here, we examined AA effects on neurotransmission, plasticity and spontaneous network activity (i.e., sharp waves and high frequency oscillations; SPW-HFOs), at the synapse between area 3 and 1 of the hippocampal cornu ammonis region (CA3 and CA1) using an extracellular multi-electrode array in in vitro mouse hippocampal slices. We found that AA decreased evoked field potentials (fEPSPs, IC50 = 0.64 mM) without affecting V50s or paired pulse facilitation indicating normal neurotransmitter release mechanisms. AA decreased presynaptic fiber volleys but did not change fiber volley-to-fEPSP coupling, suggesting reduced fEPSPs resulted from decreased fiber volleys. Inhibitory effects were also observed in CA1 stratum pyramidale where greater fEPSPs were required for population spikes in the presence of AA suggesting an impact on the intrinsic excitability of neurons. Other forms of synaptic plasticity and correlates of memory (i.e., short- and long-term potentiation) were also significantly reduced by AA as was the incidence of spontaneous SPW-HFOs. AA decreased SPW amplitude with a similar IC50 as fEPSPs (0.65 mM). Overall, these results indicate that under normal conditions AA significantly regulates neurotransmission, plasticity, and network activity by limiting excitability. Thus, AA may participate in refinement of signal processing and memory formation, as well as protecting against pathologic excitability.

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Section: Discussionmentioning

confidence: 99%

Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices

et al. 2022

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“…[4] Preclinical studies on animal models demonstrated that Vitamin C could decrease the mortality rate in rats with hypoxic brain damage and vasospasm following subarachnoid hemorrhage. ree out of four studies that evaluated the effect of Vitamin C on TBI in rats [25] concluded that AA could significantly improve the functions of rats; [29,30,48] another study showed that survival of rats was increased after a supplementary dose of Vitamin C. [23] Furthermore, Lin et al observed that disruption of the blood-brain barrier (BBB) was decreased following the administration of Vitamin C. [29] e only clinical study was carried out by were not significantly different between the control group and the patients who were administrated Vitamin C. Interestingly, perilesional edema was stable or reduced in 68% of patients receiving a high dose of Vitamin C. [37] ese results were in contrast with ours in that we observed decreased mortality of patients receiving combined Vitamins E and C and significantly shorter hospital stay in the treatment group.…”

Section: Discussionmentioning

confidence: 99%

“…This indicates the importance of AA for maintaining the function of the central nervous system. [ 18 , 21 , 25 , 38 ] Vitamin E is a fat-soluble agent and a part of the tocopherols and tocotrienols families which are shown to have significant antioxidative effects, inhibitory effects on lipoprotein oxidation, and anti-inflammatory and platelet anti-aggregation features. [ 2 , 8 , 24 ] Furthermore, evidence shows the neuroprotective effect of this vitamin and its role in nervous system development in addition to the aforementioned effects.…”

Section: Introductionmentioning

confidence: 99%

“…[ 2 , 8 , 24 ] Furthermore, evidence shows the neuroprotective effect of this vitamin and its role in nervous system development in addition to the aforementioned effects. [ 10 , 19 ] Given the scarcity of evidence on the effect of Vitamins C and E on the outcomes of patients with TBI and the remarkable primary outcomes of the present studies,[ 25 , 37 ] we aimed to examine the above-mentioned outcomes of severe TBI patients following administration of combined Vitamins C and E in a large-scale cohort.…”

Section: Introductionmentioning

confidence: 99%

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The effect of Vitamins C and E on clinical outcomes of patients with severe traumatic brain injury: A propensity score matching study

Khalili

Abdollahifard

Niakan

et al. 2022

Surgical Neurology International

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Background: The aim of this study was to assess the effect of Vitamins C and E on mortality, intensive care unit (ICU) length of stay, and Glasgow Outcome Scale-Extended (GOS-E) score of traumatic brain injury (TBI) patients. Methods: Using data from records of patients in a retrospective cohort study, we included 1321 TBI patients, 269 treated and 1052 untreated, aged over 18 years with information on exposure (i.e., Vitamins C and E) and confounders. Age, Glasgow Coma Scale, pupil status, Rotterdam classification, blood sugar, blood pressure, international normalized ratio, and comorbidity of patients were considered as the confounding factors. Endpoints were GOS-E on follow-up, mortality, and ICU length of stay. Propensity score matching was performed to adjust the confounders. Results: Based on the average treatment effect estimates, the use of Vitamins C and E reduced the risk of mortality (risk difference [RD]: −0.07; 95% confidence interval [CI]: −0.14–−0.003) and reduced the length of ICU stay (RD -1.77 95% CI:-3.71-0.16). Furthermore, our results showed that GOS-E was improved significantly (RD: 0.09, 95% CI : 0.03-0.16). Conclusion: Our study suggests that using Vitamins C and E could decrease mortality and length of ICU stay and improve the GOS-E score and functions of the patients with severe TBI. As they are safe and inexpensive medications, they can be used in routine practice in ICUs to improve the outcomes of TBI patients.

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“…Studies have indicated that vitamin C adjuvant therapy for HIE can improve the relevant antioxidant and anti-inflammatory indexes in the blood of pediatric patients and obtain better curative effects [ 21 ]. However, few studies have found no significant clinical efficacy, which cannot be ruled out as a result of the dose of vitamin C, route of administration, or other mechanisms in clinical trials for HIE [ 22 , 23 ]. At present, there is still controversy regarding the clinical efficacy of vitamin C in treating HIE.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Vitamin C Regulating Immune and Inflammation Associated with Neonatal Hypoxic-Ischemic Encephalopathy Based on Network Pharmacology and Molecular Simulation Technology

Zhao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. There are still controversies about the curative effect of vitamin C in treating HIE, and its mechanism of action is not entirely clear. This study is designed to explore the potential molecular mechanism of vitamin C in treating neonatal hypoxic ischemic encephalopathy (HIE). Methods. The effect targets of vitamin C and the pathogenic targets of neonatal HIE were obtained via retrieval of public databases to screen out the molecular targets of vitamin C acting on neonatal HIE. Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the main targets. Vitamin C and the optimum target structural components are subjected to molecular docking and molecular dynamics simulation analysis via computer software so as to verify their binding activity and stability. Result. Based on 16 overlapping targets of vitamin C and HIE, seven main targets were identified in this study. According to GO and KEGG analysis, molecular functions (top 25 items) and signal pathways (21 items) related to inflammatory reaction, immune response, and cell transcriptional control may be potential pathways for vitamin C to treat neonatal HIE. Molecular docking and molecular dynamics simulation were adopted to definitively determine the 4 optimum core target spots. Conclusion. The efficacy of vitamin C on HIE is involved in the immunoregulation and inflammation-related functional processes and signal pathways. These molecular mechanisms, including core targets, will contribute to the clinical practice of neonatal HIE in the future.

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Neuroprotective Properties of Vitamin C: A Scoping Review of Pre-Clinical and Clinical Studies

Cited by 11 publications

References 63 publications

Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices

Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices

The effect of Vitamins C and E on clinical outcomes of patients with severe traumatic brain injury: A propensity score matching study

Mechanisms of Vitamin C Regulating Immune and Inflammation Associated with Neonatal Hypoxic-Ischemic Encephalopathy Based on Network Pharmacology and Molecular Simulation Technology

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