The diabetogenic effects of chronic supplementation of vitamin C or E in rats: Interplay between liver and adipose tissues transcriptional machinery of lipid metabolism.

AIM: The chronic administration of vitamin C and E can differentially disrupt hepatic insulin molecular pathway in rats. Hence, this study evaluated their effects on lipogenesis in the liver and adipose tissue and investigated the possible involvement of microRNA (miR)-22/29a/27a in the induced impaired glucose tolerance. MAIN METHODS: Wistar rats were orally supplemented with vitamin C (100, 200, and 500 mg/kg) or vitamin E (50, 100, and 200 mg/kg) for eight months. KEY FINDINGS: Vitamin C or E at the highest doses significantly altered liver weight and index, serum and hepatic lipids, adiponectin, and liver enzymes; besides their reported unfavorable effect on glucose homeostasis. Vitamin C and E negatively affected peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), sterol regulatory element-binding protein (SREBP)-1c/-2, miR-22/29a/27a expression, and adipose perilipin 1 to different extents, effects that were supported by the histopathological examination. SIGNIFICANCE: The current study provides a deeper insight into the findings of our previous study and highlights the detrimental effects of chronic vitamins supplementation on lipid metabolism. Overall, these findings emphasize the damage caused by the mindless use of supplements and reinforce the role of strict medical monitoring, particularly during the new COVID-19 era during which numerous commercial supplements are claiming to improve immunity.

Collagen Peptides, in Association with Vitamin C, Sodium Hyaluronate, Manganese and Copper, as Part of the Rehabilitation Project in the Treatment of Chronic Low Back Pain.

BACKGROUND AND OBJECTIVE: Low back pain (LBP) is a frequent symptom. Among the causes that can determine it, lumbar osteoarthritis plays an important role. Therapeutic exercise, according to McKenzie method, has been shown to be effective in the treatment of LBP. Oral supplementation with collagen peptides represents a new therapeutic possibility in osteoarthritis. The aim of this study is to evaluate the combined efficacy of therapeutic exercise and oral administered viscosupplements in the treatment of osteoarthritis-related chronic LBP. METHODS: Sixty patients were recruited and randomly divided into two groups (Group A and B). Group A performed only kinesitherapy, Group B carried out the same kinesitherapy combined with the daily administration of food supplements such as Fortigel®, Vitamin C, sodium hyaluronate, manganese and copper, during the whole treatment period. Patients were evaluated at the time of recruitment (T0), at the end of the treatment (T1 - 3 weeks after T0) and 6 weeks after T1 (T2). The outcome measures used were: Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Short Form-12 (SF-12). RESULTS: All the outcomes improved significantly at T1 in both groups, but more markedly in group B. Furthermore, in group A at T2, there was a statistically significant worsening in the scores of VAS, ODI and physical component of the SF-12, while in group B, this variation has not been detected. CONCLUSION: The combination of rehabilitation based on McKenzie back exercises and oral viscosupplementation with Fortigel®, Vitamin C, sodium hyaluronate, manganese and copper represents a valid option in patients with chronic LBP, as it ensures pain relief and improvement in the quality of life and in lumbar spine functionality. These therapeutic benefits are more evident and long-lasting compared to those obtained with rehabilitation alone.

Antioxidants Supplementation in Acute Amitriptyline Abuse for Pain.

The fundamental aim of this study is to establish the role of antioxidant supplementation in alleviating acute amitriptyline induced oxidative stress. The effect of supplementation was compared on treatment of acute amitriptyline intoxication cases for pain management, with alpha lipoic acid (ALA) alone or with vitamin C, with that of healthy individuals (group I), and those receiving only routine standard treatment (RST) as control (group II). A total of 132 human subjects divided into 5 groups were supplemented with either placebo, RST, RST with vitamin C, RST with ALA, or RST with vitamin C, and ALA. Results of this study revealed that the decrease in the level of oxidative stress and enzyme activity was observed among those supplemented with either alpha lipoic acid alone or along with vitamin C, with a slightly more decrease in the latter group. P value of < 0.001 was considered statistically significant. The percentage of benefit of treatment on supplementation with vitamin C and alpha lipoic acid showed a marked increase in group V cases after supplementation with both in combination. The results provided that the oxidative stress induced by acute amitriptyline poisoning is comparatively decreased by supplementation with antioxidants like alpha lipoic acid and vitamin C, than those only on routine standard treatment.

High Dose Ascorbic Acid During Acute Resuscitation in Critically Burn Patients.

Ascorbic acid (AA) is a potent oxygen-free radical scavenger. We hypothesized that treating severe burn patients with high doses of AA (HDAA) can reduce fluid resuscitation requirements and prevent organ dysfunction. We performed a unicentric, retrospective case-control study of 75 burn patients: 25 patients admitted from 2018 to 2019 with more than 30% Total Surface Body Surface Area (TSBA) burned who received HDAA (66 mg/kg/h as soon as possible after admission until 36 h after injury), and 50 patients admitted from 2014 to 2017 with similar Abbreviated Burn Severity Index (ABSI)/Baux scores who were treated with the same protocol but did not receive HDAA. During the first 24 hours of burn resuscitation the HDAA group required less fluids than the control group (3.06 ± 0.87 ml/kg/%TBSA vs 4.32 ± 1.51 P < .05), but the overall reduction of fluid requirements during the first 72 hours was not significant. There were no significant differences in Sequential Organ Failure Assessment (SOFA), other hemodynamic parameters, complications, or mortality. We also did not find an increase acute kidney injury in patients who received HDAA even though the mean urine oxalate/creatinine ratio was 0.61 (0.02-0.96). We conclude that in severe burn patients treated with a restrictive fluid therapy protocol, administration of HDAA can decrease only the initial fluid requirements but not total fluid intakes. We did not find differences in severity score after resuscitation or in mortality. Nor did we find an increase in renal failure in patients administered with HDAA.

Effect of high-dose intravenous ascorbic acid on cancer patients following ketogenic diet.

BACKGROUND: The role of ascorbic acid in cancer therapy is mainly due to its structural similarity with glucose. When supplemented intravenously in high dose, ascorbic acid can get into the cancer cells and induce apoptosis by causing mitochondrial damage. AIM: The aim was to study the efficacy of high-dose intravenous (IV) ascorbic acid as monotherapy in cancer patients following ketogenic diet and its role in improving the quality of life. RESULTS: C-reactive protein (CRP) and erythrocyte sedimentation rates (ESRs) were considered as parameters to determine the efficacy of the treatment, and substantial decrease in both the levels was observed within 1-week treatment. CRP levels declined from 3.1946 ± 3.2508 mg/L to 1.0606 ± 0.6706 mg/L (P = 2.27E-10), whereas ESR levels declined from 64.1333 ± 38.8253 mm/h to 31.6 ± 16.5520 mm/h (P = 0.0041). A decline in these parameters shows the association of ascorbic acid in reducing the inflammatory response in cancer. The renal effect of ascorbic acid was also studied by analyzing the creatinine level pre- and postascorbic acid treatment sessions, and it raised from 0.8526 ± 0.22904 to 1.1666 ± 0.2894 mg/dL (P = 1.18E-14). This showed the renal impact of ascorbic acid. CONCLUSION: The study highlighted the clinical benefit of IV ascorbic acid in the reduction of inflammatory response in cancer patients. The renal adverse events associated with ascorbic acid alarm the use with caution and therapeutic drug monitoring for ascorbic acid.

High dose intravenous vitamin C treatment in Sepsis: associations with acute kidney injury and mortality.

BACKGROUND: The effects of vitamin C on clinical outcomes in critically ill patients remain controversial due to inconclusive studies. This retrospective observational cohort study evaluated the effects of vitamin C therapy on acute kidney injury (AKI) and mortality among septic patients. METHODS: Electronic medical records of 1390 patients from an academic hospital who were categorized as Treatment (received at least one dose of 1.5 g IV vitamin C, n = 212) or Comparison (received no, or less than 1.5 g IV vitamin C, n = 1178) were reviewed. Propensity score matching was conducted to balance a number of covariates between groups. Multivariate logistic regressions were conducted predicting AKI and in-hospital mortality among the full sample and a sub-sample of patients seen in the ICU. RESULTS: Data revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46-2.93]) and in-hospital mortality (OR = 1.67 95% CI [1.003-2.78]) after adjusting for demographic and clinical covariates. When stratified to examine ICU patients, vitamin C therapy remained a significant risk factor of AKI (OR = 1.61 95% CI [1.09-2.39]) and provided no protective benefit against mortality (OR = 0.79 95% CI [0.48-1.31]). CONCLUSION: Ongoing use of high dose vitamin C in sepsis should be appraised due to observed associations with AKI and death.

Micronutrients and athletic performance: A review.

Optimising nutrition intake is a key component for supporting athletic performance and supporting adaption to training. Athletes often use micronutrient supplements in order to correct vitamin and mineral deficiencies, improve immune function, enhance recovery and or to optimise their performance. The aim of this review was to investigate the recent literature regarding micronutrients (specifically iron, vitamin C, vitamin E, vitamin D, calcium) and their effects on physical performance. Over the past ten years, several studies have investigated the impacts of these micronutrients on aspects of athletic performance, and several reviews have aimed to provide an overview of current use and effectiveness. Currently the balance of the literature suggests that micronutrient supplementation in well-nourished athletes does not enhance physical performance. Excessive intake of dietary supplements may impair the body's physiological responses to exercise that supports adaptation to training stress. In some cases, micronutrient supplementation is warranted, for example, with a diagnosed deficiency, when energy intake is compromised, or when training and competing at altitude, however these micronutrients should be prescribed by a medical professional. Athletes are encouraged to obtain adequate micronutrients from a wellbalanced and varied dietary intake.

Hepatoprotective, antioxidant and anti-inflammatory potentials of Vit-E/C@SeNPs in rats: Synthesis, characterization, biochemical, radio-biodistribution, molecular and histopathological studies.

This study aimed to synthesize a nano-structure between selenium, Vit. C, and Vit. E (Vit-E/C@SeNPs) as a promising protective and therapeutic agent for hepatocellular carcinoma. Vit-E/C@SeNPs were characterized using TEM and DLS and its zetapotential was measured to evaluate its stability. DPPH assay and SRB test were performed to estimate its antioxidant capacity and cytotoxicity, respectively. A radiosynthesis of 99mTc-Vit-E/C@SeNPs was done for further in-vivo pharmacokinetic studies on normal and solid tumor induced mice. Further, in-vivo studies were conducted to investigate Vit-E/C@SeNPs efficacy against hepatocellular damage in Wistar albino rats induced by diethylnitrosamine (DEN) / Carbon Tetra chloride (CCl4). The synthesis results showed spherical Vit-E/C@SeNPs with core size of 50 nm, radical scavenging activity (%RSC) of 75.9%, and IC50 of 27.9 µg/ml. The biochemical analysis results showed that the lower liver function biomarker values (ALT, AST, ALP, total bilirubin and GGT) has gone for the Vit-E/C@SeNPs prevention and treated group, which also showed significant depletion of liver tissue l-MDA, and obvious increase in GSH concentration and CAT activity and marked improvement in the histological feature of liver tissue. Additionally, a significant up-regulation of mRNA gene expression levels of inflammatory gene (TGFß1, NFκB, iNOS, PPAR-γ and TNFα) and Apoptotic gene (P53) were determined by using Quantitative real-time PCR (qPCR). The values down regulate and tend to normal in prevention and control group. All of these introduce Vit-E/C@SeNPs as a promising agent as protective and therapeutic agent against DEN/ CCl4-induced hepatocellular damage (Hepatocellular carcinoma).

Effect of Lactobacillus fermentum HFY03 on the Antifatigue and Antioxidation Ability of Running Exhausted Mice.

Yak yogurt is mainly produced in Qinghai-Tibet Plateau. It is a kind of naturally fermented dairy product. It contains abundant microorganisms. Lactobacillus fermentum (LF) HFY03 is a lactic acid bacteria derived from it. Our main research content is to study the influence of LF-HFY03 on the antifatigue and antioxidation ability of running exhausted mice. We gave different doses of LF-HFY03 to mice by gavage for 4 weeks. We selected vitamin C as the positive control group, mainly to study the relationship between antioxidant capacity and fatigue resistance and LF-HFY03 in mice with running exhaustion. The results showed that LF-HFY03 and vitamin C could significantly improve the running time of mice. And with the increase in LF-HFY03 concentration, the exhaustion time of mice was also extended. LF-HFY03 can reduce the content of urea nitrogen and lactic acid and also can increase the content of free fatty acids and liver glycogen. The levels of alanine aminotransferase, serum creatine kinase, and aspartate aminotransferase in mice decreased gradually as the antioxidant peptide level of walnut albumin increased. LF-HFY03 can reduce malondialdehyde (MDA) levels in a quantification-dependent manner and can also increase catalase (CAT) and superoxide dismutase (SOD) levels. LF-HFY03 can also increase the expressions of CAT mRNA, Cu/Zn-SOD, and Mn-SOD in the liver of mice. At the same time, LF-HFY03 can also increase the expression of protein of threonine transporter 1 (AST1)/alanine/cysteine/serine, mRNA, nNOS, and eNOS. At the same time, the solution could reduce the expression of TNF-α, syncytin-1, and inducible nitric oxide synthase (iNOS). The results showed that LF-HFY03 has a high development and application prospect as an antifatigue probiotic nutritional supplement.

Impact of vitamin C supplementation on placental DNA methylation changes related to maternal smoking: association with gene expression and respiratory outcomes.

BACKGROUND: Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes. RESULTS: DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate "restored CpGs" for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers. CONCLUSIONS: Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696 .

Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3-10 years: randomised controlled trial.

In a double-blind, randomised, parallel-group, placebo-controlled study, healthy school children aged 3-10 years received a probiotic based supplement daily for 6 months to assess the impact on the incidence and duration of upper respiratory tract infection (URTI) symptoms. The intervention comprised Lab4 probiotic (Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) at 12.5 billion cfu/day plus 50 mg vitamin C or a matching placebo. 171 children were included in the analysis (85 in placebo and 86 in active group). Incidence of coughing was 16% (P=0.0300) significantly lower in the children receiving the active intervention compared to the placebo. No significant differences in the incidence rate of other URTI symptoms were observed. There was significantly lower risk of experiencing five different URTI related symptoms in one day favouring the active group (Risk ratio: 0.31, 95% confidence interval: 0.12, 0.81, P=0.0163). Absenteeism from school and the use of antibiotics was also significantly reduced for those in the active group (-16%, P=0.0060 and -27%, P=0.0203, respectively). Our findings indicate that six months daily supplementation with the Lab4 probiotic and vitamin C combination reduces the incidence of coughing, absenteeism and antibiotic usage in 3 to 10 year old children.

Any Role of High-Dose Vitamin C for Septic Shock in 2021?

While the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 µmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.

Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study.

Ascorbic acid represents an appealing option for clinicians to utilize in the context of the global COVID-19 pandemic due to its proposed clinical efficacy, relative safety, and low cost. The aim of this study was to evaluate the efficacy and safety of using ascorbic acid in supplemental doses as adjunctive therapy for patients critically ill with COVID-19. This was a two-center, non-interventional, retrospective cohort study. All critically ill adult patients admitted to ICU with a confirmed COVID-19 diagnosis between March 1st and December 31st, 2020, were included in the final analysis. The study was conducted at two large governmental tertiary hospitals in Saudi Arabia. The purpose was to investigate the clinical outcomes of low-dose ascorbic acid as adjunctive therapy in COVID-19 after propensity score matching using baseline severity scores, systematic use of corticosteroids, and study centers. A number of 739 patients were included in this study, among whom 296 patients were included after propensity score matching. There was no association between the administration of ascorbic acid and in-hospital mortality or the 30-day mortality [OR (95% CI) 0.77 (0.47, 1.23), p value = 0.27 and OR (95% CI) 0.73 (0.43, 1.20), p value = 0.21, respectively]. Using ascorbic acid was associated with a lower incidence of thrombosis compared with the non-ascorbic-acid group [6.1% vs. 13% respectively; OR (95% CI) 0.42 (0.184, 0.937), p value = 0.03]. Low dose of ascorbic acid as an adjunctive therapy in COVID-19 critically ill patients was not associated with mortality benefits, but it was associated with a lower incidence of thrombosis. Further studies are required to confirm these findings.

Clinical efficacy and safety of oral and intravenous vitamin C use in patients with malignant diseases.

BACKGROUND: Vitamin C, also called ascorbic acid, is a water-soluble antioxidant and free radical scavenger. It is required in the body for numerous metabolic functions and is involved in the development of proteins and connective tissue. METHODS: In April 2020, a systematic search was carried out on five electronic databases (Medline, Embase, Cochrane, Cinahl, PsycINFO) to find studies on the use, efficacy and safety of a complementary therapy with vitamin C in oncological patients. RESULTS: Out of the initial 23,195 search results, 21 studies with 1961 patients were included in this review. Five of the included studies (n = 417) were randomized controlled trials (RCTs). The remaining 16 studies belonged to a lower class of evidence. The patients who were treated with vitamin C suffered from various malignant diseases, some in an advanced and palliative stage. Vitamin C was applied intravenously or orally. It was either the only treatment or was combined with chemo- or radiotherapy. Endpoints included the development of the disease-related symptoms, quality of life, mortality, progression-free survival and safety of vitamin C. The studies were of moderate quality and showed either no effect of vitamin C or a positive trend, although this has rarely been statistically proven in group comparisons. No or only slight side effects with both oral and intravenous administration of vitamin C were reported. CONCLUSION: Oral intake of vitamin C does not appear to have any effect in patients with malignancies. Data are heterogeneous for intravenous administration. There are no RCTs with statistical group comparisons.

Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review.

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

Efficacy of intravenous vitamin C intervention for septic patients: A systematic review and meta-analysis based on randomized controlled trials.

BACKGROUND: The role of vitamin C in sepsis is still controversial, we aimed to systematically review the efficacy of intravenous vitamin C supplementation in the treatment of sepsis. METHODS: MEDLINE, EmBase, Web of Science, WanFang Data and CNKI were comprehensively searched to collect randomized controlled trails (RCTs) of vitamin C supplementation for patients with sepsis or sepsis shock from January 2000 to March 2021. Two researchers independently screened the literature, extracted the data and accessed the risk of bias in the included studies; meta-analysis was then performed by using Revman 5.4 software. RESULTS: A total of 10 RCTs involving 1400 participants were included. The results of meta-analysis showed that intravenous vitamin C supplementation can improve SOFA (ΔSOFA) within 72 h [RR = 1.32,95% CI(0.80,1.85), P < 0.0001] of septic patients. There were no difference on short term mortality (28-30d)[RR = 0.83,95% CI(0.65,1.05), P = 0.11], long term mortality (90d) [RR = 1.16,95% CI(0.82,1.66), P = 0.40], hospital LOS[RR = 0.15,95% CI(-0.73,1.03), P = 0.55], ventilator-free days[RR = 0.09,95% CI(-0.24,0.42), P = 0.60], ICU-LOS[RR = 0.22,95% CI(-0.13,0.57), P = 0.22], between two groups. The results of Subgroup analysis showed that intravenous vitamin C alone can reduce the risk of short term mortality (28-30d) [RR = 0.61,95% CI(0.47,0.79), P = 0.0002]of sepsis patients. CONCLUSION: Based on current RCTs, our work indicated that mono-intravenous vitamin C therapy may reduce short-term mortality of sepsis patients, and it may protect organ functions. Due to the limitation of the quantity and quality of included studies, the above conclusions need to be verified by more large scale and high quality randomized control trials.

Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats.

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.

Vitamin C and D supplementation and the severity of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has rapidly spread to other countries, causing numerous deaths and challenges for organizations and health professionals. Diet and nutrition invariably influence the competence of the immune system and determine the risk and severity of infections. Studies have already been published on the relationships through which vitamins C and D can mitigate the severity of infections such as COVID-19. In this context, this protocol describes a systematic review intended to analyze if vitamin C and D supplementation can reduce the severity of Covid-19. METHODS: This protocol was developed based on the recommendations of PRISMA-P. In order to accomplish the systematic review, we will carry out searches in the PubMed, Web of Science, Scopus, Cochrane, and ScienceDirect databases in the quest for control case studies that analyze the supplementation and evolution of patients with COVID-19. There will be no limitations related to language or publication time. The searches will be carried out by 2 independent researchers who will select the articles, and then the duplicate studies will be removed, while the suitable ones will be selected using the Rayyan QCRI application. In order to assess the risk of bias, we will use the instrument proposed by the National Heart, Lung and Blood Institute. Moreover, we will carry out metaanalyses and subgroup analyses according to the conditions of the included data. RESULTS: This review will assess the association between vitamin C and D supplementation and the reduction in the severity of COVID-19. CONCLUSION: The findings of this systematic review will summarize the latest evidence for the association between vitamin C and D supplementation and COVID-19 through a systematic review and meta-analysis. RECORD OF SYSTEMATIC REVIEW: CRD42021255763.

Effect of Vitamin C on mortality of critically ill patients with severe pneumonia in intensive care unit: a preliminary study.

BACKGROUND: Critically ill patients frequently suffer from vitamin C deficiency. Previous studies showed that high doses of vitamin C administration had conflicting results on clinical outcomes in patients with severe sepsis, burns, and trauma. Because of the high incidence and morbidity/mortality with severe pneumonia, we aimed to investigate the effect of administration of high dose vitamin C in critically ill patients with severe pneumonia. METHODS: Eighty critically ill patients with pneumonia were enrolled in this randomized double-blinded clinical trial. Patients with a CURB-65 score > 3, one major criterion, or ≥ 3 minor criteria were considered as severe pneumonia. Patients were randomly assigned to intervention or placebo groups receiving standard treatment plus 60 mg/kg/day vitamin C as a continuous infusion or normal saline in the same volume correspondingly for 96 h. Serum levels of vitamin C were noted at baseline and 48 h after vitamin C administration. Duration of mechanical ventilation, ICU length of stay, PaO2/FiO2, and mortality rate were noted for all patients till the 28th day. Any complications related to the vitamin C administration were recorded. RESULTS: Duration of mechanical ventilation and vasopressor use were significantly lower in the intervention group (p: < 0.001 and 0.003, respectively). Baseline levels of vitamin C in both groups did not have a significant difference but its levels increased in the intervention group and decreased in the control group during the study period. Mortality rate insignificantly decreased in the intervention group (p = 0.17). Three patients showed hypotension and tachycardia during the administration of vitamin C which was self-limited with decreasing the dose of vitamin C. Our results showed that the intravenous administration of a relatively high dose of vitamin C to critically ill patients with severe pneumonia was safe and could decrease the inflammation, duration of mechanical ventilation, and vasopressor use without any significant effect on mortality. TRIAL REGISTRATION: IRCT registration number: IRCT20190312043030N1, Registration date: 2019-08-26, Seied Hadi Saghaleini.