Synchronizing positive effect of vitamin C and chromium on hyper lipidemia, hyperglycemia, liver enzymes and BMI of diabetes mellitus type 2 patients.

This study investigates the combined effect of vitamin C and chromium on BMI, lipid profile, LFTs and HbA1c of Diabetes Mellitus type 2 patients. This is randomized controlled trial study. For this study a total of 60 patients (n=28 female, n=32 male) Diabetes Mellitus type 2 patients were selected. They were divided into treatment group (vitamin C (500mg) Chromium (200µg) and control group (placebo) comprising thirty patients per group. Mean age in control group and treatment group is 33± 5.729 and 33±7.017 respectively. Statistical analysis showed significant results of lipid profile; total cholesterol (mg/dl) 198±66.1 P=0.008, High-Density Lipoprotein 38±7.5, P<0.001, Low Density Lipoprotein (LDL) (mg/dl) 105.1±22.4, P=0.002 and Triglycerides 191±64.3, P=0.02 are respectively. Levels of serum ALT (u/l) (34.7±9.1, P<0.001) and AST (u/l) (31.6 ±8.6, P<0.001) were significantly lower as compared to control group. HbA1c percentages were also normalized (5.45±0.2, P<.001) as compared to group 2. BMI values were also improved (P=0.01) after treatment. Combined supplementation of vitamin C and chromium reduce the plasma lipid percentage, blood glucose levels and also improve the ALT and AST functions.

Scurvy masquerading as IgA vasculitis.

BACKGROUND: Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with restrictive or selective dietary habits in children with global developmental delay, autism spectrum disorder, and physical disabilities. Symptoms include fatigue, irritability, joint and muscle pain, joint swellings, edema, swollen gums, easy bruising, and delayed wound healing. Early recognition and prompt intervention are essential to prevent the progression of symptomatic vitamin C deficiency in children. CASE PRESENTATION: We present a case of a 13-year-old boy with developmental delay secondary to Lennox Gastaut syndrome referred for suspected recurrent, severe, and atypical IgA vasculitis. He presented with irritability, loss of appetite, petechial and ecchymotic lower limb lesions, unilateral gum swelling, severe arthritis, peripheral oedema, severe weight loss, anaemia, and raised inflammatory markers. Multiple investigations were performed before the diagnosis of scurvy was made. A surgical finding of friable gingival tissue with multiple loose teeth, a skin biopsy with follicular hyperkeratosis and extravasated perifollicular red blood cells, and a typical X-ray finding led to the diagnosis of scurvy. CONCLUSION: Scurvy should be given careful consideration as a differential diagnosis in patients presenting with musculoskeletal issues, mucocutaneous complaints, and constitutional symptoms such as malaise, asthenia, irritability, and loss of appetite. A focused and detailed dietary history looking for a lack of good sources of vitamin C can be an easy indicator of this differential. Imaging studies revealing the typical features can also help make the diagnosis. Pathology of the skin revealing pathognomonic features can add to the certainty of the diagnosis. In the absence of all else, the rapid response to treatment with an appropriate dose of vitamin C has a diagnostic and therapeutic role.

The Efficacy of Multivitamin, Vitamin A, Vitamin B, Vitamin C, and Vitamin D Supplements in the Prevention and Management of COVID-19 and Long-COVID: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials.

This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023 to identify randomized clinical trials comparing data on the effects of vitamin supplementation(s) versus placebo or standard of care on the two conditions of interest. Inverse-variance random-effects meta-analyses were conducted to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality between supplemented and non-supplemented individuals. Overall, 37 articles were included: two regarded COVID-19 and long-COVID prevention and 35 records the COVID-19 management. The effects of vitamin D in preventing COVID-19 and long-COVID were contrasting. Similarly, no conclusion could be drawn on the efficacy of multivitamins, vitamin A, and vitamin B in COVID-19 management. A few positive findings were reported in some vitamin C trials but results were inconsistent in most outcomes, excluding all-cause mortality (RR = 0.84; 95% CI: 0.72-0.97). Vitamin D results were mixed in most aspects, including mortality, in which benefits were observed in regular administrations only (RR = 0.67; 95% CI: 0.49-0.91). Despite some benefits, results were mostly contradictory. Variety in recruitment and treatment protocols might explain this heterogeneity. Better-designed studies are needed to clarify these vitamins' potential effects against SARS-CoV-2.

Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The primary challenge encountered by individuals diagnosed with endometriosis is the experience of pain. Emerging research indicates that oxidative stress is implicated in the initiation of pain associated with endometriosis. Vitamins C and E are known for their antioxidative properties. The primary objective of this study is to assess the efficacy of antioxidant supplementation, consisting of these vitamins, in the management of pain associated with endometriosis. METHODS: A comprehensive search was conducted on the ClinicalTrials.gov, Scopus, Europe PMC, and Medline databases up until August 23rd, 2023, utilizing a combination of relevant keywords. This review incorporates literature that examines the relationship between antioxidant supplementation and pain in endometriosis. We employed fixed-effect models to analyze the risk ratio (RR) and present the outcomes together with their corresponding 95% confidence intervals (CI). RESULTS: A total of five RCTs were incorporated. The results of our meta-analysis indicated that antioxidant supplementation with vitamin C and E combination was associated with higher proportion of endometriosis patients reporting reduced chronic pelvic pain (RR 7.30; 95%CI: 3.27-16.31, p<0.00001, I2 = 0%), alleviations of dysmenorrhea (RR 1.96; 95%CI: 1.25-3.07, p = 0.003, I2 = 39%), and dyspareunia (RR 5.08; 95%CI: 2.10-12.26, p = 0.0003, I2 = 0%) than patients only receiving placebo. CONCLUSIONS: This study suggests the potential ability of vitamin C and E in alleviating pain symptoms experienced by individuals with endometriosis.

Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis.

Community-acquired pneumonia (CAP) poses a significant global health challenge, prompting exploration of innovative treatments. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of vitamin C supplementation in adults undergoing treatment for CAP. A comprehensive search of the MEDLINE, Embase, CINAHL, the Cochrane Central Register of Controlled Trials, and Clinical Trials.gov databases from inception to 17 November 2023 identified six randomized-controlled-trials (RCTs) meeting inclusion criteria. The primary outcome analysis revealed a non-significant trend towards reduced overall mortality in the vitamin C group compared to controls (RR 0.51; 95% CI 0.24 to 1.09; p = 0.052; I2 = 0; p = 0.65). Sensitivity analysis, excluding corona-virus-disease 2019 (COVID-19) studies and considering the route of vitamin C administration, confirmed this trend. Secondary outcomes, including hospital length-of-stay (LOS), intensive-care-unit (ICU) LOS, and mechanical ventilation, exhibited mixed results. Notably, heterogeneity and publication bias were observed in hospital LOS analysis, necessitating cautious interpretation. Adverse effects were minimal, with isolated incidents of nausea, vomiting, hypotension, and tachycardia reported. This meta-analysis suggests potential benefits of vitamin C supplementation in CAP treatment. However, inconclusive findings and methodological limitations warrants cautious interpretation, emphasising the urgency for high-quality trials to elucidate the true impact of vitamin C supplementation in CAP management.

Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

Currently, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are considered to be the main causes of fibrosis. In turn, fibrosis may lead to the development of hepatocellular carcinoma or advanced cirrhosis, i.e., potentially life-threatening conditions. It is likely that therapy aimed at reducing the risk of developing hepatic steatosis and inflammation could be helpful in minimizing the threat/probability of organ fibrosis. In recent years, increasing attention has been paid to the influence of nutraceuticals in the prevention and treatment of liver diseases. Therefore, the aim of this review was to describe the precise role of selected ingredients such as vitamin C, beta-carotene, omega-3 fatty acids, and curcumin. It is likely that the use of these ingredients in the treatment of patients with MASLD/MASH, along with behavioral and pharmacological therapy, may have a beneficial effect on combating inflammation, reducing oxidative stress, and thereby preventing liver damage.

Antioxidant supplementation for sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When subjected to oxidative stress from low oxygen concentrations, HbS molecules form rigid polymers, giving the red cell the typical sickle shape. Antioxidants have been shown to reduce oxidative stress and improve outcomes in other diseases associated with oxidative stress. Therefore, it is important to review and synthesize the available evidence on the effect of antioxidants on the clinical outcomes of people with SCD. OBJECTIVES: To assess the effectiveness and safety of antioxidant supplementation for improving health outcomes in people with SCD. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 15 August 2023. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing antioxidant supplementation to placebo, other antioxidants, or different doses of antioxidants, in people with SCD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed the risk of bias and certainty of the evidence, and reported according to Cochrane methodological procedures. MAIN RESULTS: The review included 1609 participants in 26 studies, with 17 comparisons. We rated 13 studies as having a high risk of bias overall, and 13 studies as having an unclear risk of bias overall due to study limitations. We used GRADE to rate the certainty of evidence. Only eight studies reported on our important outcomes at six months. Vitamin C (1400 mg) plus vitamin E (800 mg) versus placebo Based on evidence from one study in 83 participants, vitamin C (1400 mg) plus vitamin E (800 mg) may not be better than placebo at reducing the frequency of crisis (risk ratio (RR) 1.18, 95% confidence interval (CI) 0.64 to 2.18), the severity of pain (RR 1.33, 95% CI 0.40 to 4.37), or adverse effects (AE), of which the most common were headache, nausea, fatigue, diarrhoea, and epigastric pain (RR 0.56, 95% CI 0.31 to 1.00). Vitamin C plus vitamin E may increase the risk of SCD-related complications (acute chest syndrome: RR 2.66, 95% CI 0.77 to 9.13; 1 study, 83 participants), and increase haemoglobin level (median (interquartile range) 90 (81 to 96) g/L versus 93.5 (84 to 105) g/L) (1 study, 83 participants) compared to placebo. However, the evidence for all the above effects is very uncertain. The study did not report on quality of life (QoL) of participants and their caregivers, nor on frequency of hospitalization. Zinc versus placebo Zinc may not be better than placebo at reducing the frequency of crisis at six months (rate ratio 0.62, 95% CI 0.17 to 2.29; 1 study, 36 participants; low-certainty evidence). We are uncertain whether zinc is better than placebo at improving sickle cell-related complications (complete healing of leg ulcers at six months: RR 2.00, 95% CI 0.60 to 6.72; 1 study, 34 participants; very low-certainty evidence). Zinc may be better than placebo at increasing haemoglobin level (g/dL) (MD 1.26, 95% CI 0.44 to 1.26; 1 study, 36 participants; low-certainty evidence). The study did not report on severity of pain, QoL, AE, and frequency of hospitalization. N-acetylcysteine versus placebo N-acetylcysteine (NAC) 1200 mg may not be better than placebo at reducing the frequency of crisis in SCD, reported as pain days (rate ratio 0.99 days, 95% CI 0.53 to 1.84; 1 study, 96 participants; low-certainty evidence). Low-certainty evidence from one study (96 participants) suggests NAC (1200 mg) may not be better than placebo at reducing the severity of pain (MD 0.17, 95% CI -0.53 to 0.87). Compared to placebo, NAC (1200 mg) may not be better at improving physical QoL (MD -1.80, 95% CI -5.01 to 1.41) and mental QoL (MD 2.00, 95% CI -1.45 to 5.45; very low-certainty evidence), reducing the risk of adverse effects (gastrointestinal complaints, pruritus, or rash) (RR 0.92, 95% CI 0.75 to 1.14; low-certainty evidence), reducing the frequency of hospitalizations (rate ratio 0.98, 95% CI 0.41 to 2.38; low-certainty evidence), and sickle cell-related complications (RR 5.00, 95% CI 0.25 to 101.48; very low-certainty evidence), or increasing haemoglobin level (MD -0.18 g/dL, 95% CI -0.40 to 0.04; low-certainty evidence). L-arginine versus placebo L-arginine may not be better than placebo at reducing the frequency of crisis (monthly pain) (RR 0.71, 95% CI 0.26 to 1.95; 1 study, 50 participants; low-certainty evidence). However, L-arginine may be better than placebo at reducing the severity of pain (MD -1.41, 95% CI -1.65 to -1.18; 2 studies, 125 participants; low-certainty evidence). One participant allocated to L-arginine developed hives during infusion of L-arginine, another experienced acute clinical deterioration, and a participant in the placebo group had clinically relevant increases in liver function enzymes. The evidence is very uncertain whether L-arginine is better at reducing the mean number of days in hospital compared to placebo (MD -0.85 days, 95% CI -1.87 to 0.17; 2 studies, 125 participants; very low-certainty evidence). Also, L-arginine may not be better than placebo at increasing haemoglobin level (MD 0.4 g/dL, 95% CI -0.50 to 1.3; 2 studies, 106 participants; low-certainty evidence). No study in this comparison reported on QoL and sickle cell-related complications. Omega-3 versus placebo Very low-certainty evidence shows no evidence of a difference in the risk of adverse effects of omega-3 compared to placebo (RR 1.05, 95% CI 0.74 to 1.48; 1 study, 67 participants). Very low-certainty evidence suggests that omega-3 may not be better than placebo at increasing haemoglobin level (MD 0.36 g/L, 95% CI -0.21 to 0.93; 1 study, 67 participants). The study did not report on frequency of crisis, severity of pain, QoL, frequency of hospitalization, and sickle cell-related complications. AUTHORS' CONCLUSIONS: There was inconsistent evidence on all outcomes to draw conclusions on the beneficial and harmful effects of antioxidants. However, L-arginine may be better than placebo at reducing the severity of pain at six months, and zinc may be better than placebo at increasing haemoglobin level. We are uncertain whether other antioxidants are beneficial for SCD. Larger studies conducted on each comparison would reduce the current uncertainties.

The Involvement of Ascorbic Acid in Cancer Treatment.

Vitamin C (VC), also known as ascorbic acid, plays a crucial role as a water-soluble nutrient within the human body, contributing to a variety of metabolic processes. Research findings suggest that increased doses of VC demonstrate potential anti-tumor capabilities. This review delves into the mechanisms of VC absorption and its implications for cancer management. Building upon these foundational insights, we explore modern delivery systems for VC, evaluating its use in diverse cancer treatment methods. These include starvation therapy, chemodynamic therapy (CDT), photothermal/photodynamic therapy (PTT/PDT), electrothermal therapy, immunotherapy, cellular reprogramming, chemotherapy, radiotherapy, and various combination therapies.

High-dose vitamin C improves norepinephrine level in patients with septic shock: A single-center, prospective, randomized controlled trial.

BACKGROUND: The effects of vitamin C supplementation on patients with septic shock remain controversial. We aimed to evaluate the effects of different vitamin C dosages on norepinephrine (NE) synthesis in adult patients with septic shock. METHODS: A total of 58 patients with septic shock admitted to our intensive care unit (ICU) between July 2021 and December 2022 were included. Patients were randomly divided into 3 groups: high-dose vitamin C (150 mg/kg/d, group A), low-dose vitamin C (50 mg/kg/d, group B), and placebo (group C). NE synthesis-related indicators (dopamine-ß-hydroxylase [DßH], tyrosine hydroxylase [TH], tetrahydrobiopterin [BH4], and dopamine [DA]), plasma NE, and vitamin C levels were measured every 24 hours and analyzed. All-cause mortality within 28 days and other clinical outcomes (including Acute Physiology and Chronic Health Evaluation [APACHE], Sequential Organ Failure Assessment [SOFA], and Multiple-Organ Dysfunction Syndrome [MODS] scores) were compared. RESULTS: Changes in TH, BH4, and DßH levels at 96 hours in groups A and B were greater than those in group C. These differences became more pronounced over the course of the intravenous vitamin C administration. Significant differences between groups A and C were detected at 96-hours TH, 72-hours BH4, 96-hours BH4, 96-hours DA, and DßH levels every 24 hours. The 96-hours TH, 96-hours BH4, and 48-hours DßH in group B were significantly higher than those in group C. The NE levels every 24 hours in groups A and B were higher than those in group C, group A and group C had a statistically significant difference. The 96-hours exogenous NE dosage in groups A and B was significantly lower than that in group C. No significant reductions in APACHE, SOFA, or MODS scores were observed in the vitamin C group, including the duration of ICU stay and mechanical ventilation. The 28-days mortality was lower in groups A and B than in group C (0%, 10%, and 16.67%, P = .187), but the difference was not significant. CONCLUSION: For patients with septic shock, treatment with vitamin C significantly increased TH, BH4, and DßH levels and reduced the exogenous NE dosage, but did not significantly improve clinical outcomes.

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.

A rare case of methemoglobinemia in a preterm newborn with unclear etiology.

 Cyanosis is a bluish discoloration of the tissues due to increased levels of deoxygenated hemoglobin in capillaries. It is a common finding in newborn infants that can be caused by different diseases, including pulmonary, cardiac, infectious, and hematological disorders. Methemoglobinemia is a rare cause of cyanosis, in which hemoglobin is oxidized, changing its heme iron configuration from the ferrous (Fe2 +) to the ferric (Fe3 +) state, creating methemoglobin (Met-Hb), a form that does not bind oxygen, leading to decreased oxygen delivery to the tissues and cyanosis. We report a rare case of a preterm newborn, who developed cyanosis and worsening hypoxemia on day ten of life, she was found to have elevated Met-Hb percentage in blood gas analysis that required treatment with intravenous methylene blue. Her symptoms resolved after a period of maintenance treatment with oral methylene blue and ascorbic acid, and the etiology of her disease remains unclear.

Vitamin C alleviates rheumatoid arthritis by modulating gut microbiota balance.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetric in-flammation. Our previous research revealed an imbalance in the gut flora of RA patients and showed that certain gut microbiota can accelerate RA progression by enhancing vitamin C degradation. However, it is unclear whether vitamin C supplementation could improve the gut microbiota to prevent the development of arthritis by interfering with the gut-joint axis. In this work, we aimed to evaluate the effects of vitamin C in regulating the gut microbiota and to elucidate its potential role in the onset and progression of RA in a mouse model, thus providing a basis for the development of new intervention strategies and treatments for RA. In this study, collagen-induced arthritis (CIA) mouse models, biochemical, histological and 16S rRNA microbiological methods were used to investigate the role and possible mechanism of vitamin C in rheumatoid arthritis. The results showed that treatment of CIA mice with vitamin C effectively rescued the gut mi-crobiota imbalance and suppressed the inflammatory response associated with RA, and effectively alleviated arthritis symptoms in mice in which levels of the pro-inflammatory cytokines IL-6 and TNF-α were specifi-cally reduced. In conclusion, our results demonstrate the potential of vitamin C as a potential therapeutic choice for RA.

Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction.

Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, reperfusion after an ischemic insult and sudden oxygen exposure lead to the exacerbated synthesis of additional reactive oxidative species and the persistence of increased oxidation levels. Attempts based on antioxidant treatment have failed to achieve an effective therapy for cardiovascular disease patients. The controversial use of vitamin C as an antioxidant in clinical practice is comprehensively systematized and discussed in this review. The dose-dependent adsorption and release kinetics mechanism of vitamin C is complex; however, this review may provide a holistic perspective on its potential as a preventive supplement and/or for combined precise and targeted therapeutics in cardiovascular management therapy.

The effects of vitamin C supplementation in the critically ill patients outcomes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin C has significant anti-inflammatory effects and is particularly important for critically ill patients. However due to inconsistent research findings in critically ill patients in meta-analysis. Therefore, the primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness by comprehensively incorporating articles from randomized controlled trials. METHODS: Articles included searching through PubMed, Embase, Medline, Cochrane Library, and Web of Science up to April 28, 2023, for articles on vitamin C and the critically ill. We calculated pooled standard relative risk (RR), mean difference (MD), and 95% confidence intervals (CIs). And the protocol for the review has been registered on PROSPERO (CRD42023425193). RESULTS: There are 2047 critically ill included in 19 articles. Compared with placebo, patients who underwent intravenous vitamin C (IVVC) have reduced duration of vasopressor used (SMD 0.26; CI 0.01-0.51; I2 = 87.0%, P = .044), mechanical ventilation (SMD -0.29; CI -0.55 to -0.03; I2 = 36.8%, P = .031). However, the administration of IVVC had no statistical difference in 28-d mortality (RR 0.95; CI 0.80-1.11; I2 = 12.2%, P = .337), mortality (RR 0.79; CI 0.55-1.12; I2 = 0%, P = .188), fluid intake (SMD -0.02; CI -0.25 to 0.20; I2 = 0%, P = .838), urine output (SMD 0.23; CI -0.03 to 0.49; I2 = 0%, P = .084), ICU days (SMD 0.10; CI -0.03 to 0.22; I2 = 0%, P = .127), hospital stay (SMD 0.10; CI -0.12 to 0.32; I2 = 0%, P = .375), and pneumonia (RR 0.85; CI 0.50-1.44; I2 = 0%, P = .552). CONCLUSION: This study comprehensively and systematically evaluated IVVC supplementation in the critically ill through a meta-analysis of RCT. There is no difference except for patients who had reduced duration of vasopressor use and mechanical ventilation by the administration of IVVC. Of course. More scientific and rigorous conclusions can be drawn from multi-center RCT research in the future.

Role of vitamin C in treatment of community-acquired pneumonia in adult patients requiring hospitalisation: a systematic review protocol.

INTRODUCTION: Community-acquired pneumonia (CAP) is a leading cause of hospitalisation and is associated with a high mortality. Vitamin C is a powerful antioxidant and has been used in treatment of infections; however, its role as an adjunctive treatment in CAP is unclear. This review aims to assess the efficacy and safety of vitamin C in adults who require hospitalisation for CAP. METHODS AND ANALYSES: Searches will be conducted from inception to November 2023 on Ovid MEDLINE Daily and MEDLINE, Embase CINAHL, the Cochrane Central Register of Controlled Trials, Scopus, Web of Science and ClinicalTrials.gov databases with the aid of a medical librarian. We will include data from randomised controlled trials reporting vitamin C supplementation in patients with CAP requiring hospitalisation. Two independent reviewers will select studies, extract data and will assess the risk of bias by use of the Risk of Bias tool. The overall certainty of evidence will be assessed by use of the Grading of Recommendations Assessment, Development and Evaluation framework. Random-effects meta-analyses will be conducted, and effect measures will be reported as relative risks with 95% CIs. ETHICS AND DISSEMINATION: No previous ethical approval is required for this review. The findings of this review will be submitted to a scientific journal and presented at an international medical conference. PROSPERO REGISTRATION NUMBER: 483860.

Effect of high-dose vitamin C on renal ischemia-reperfusion injury.

Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague-Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200 mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300 mg/kg, respectively). Renal I/R was achieved through 45 min of ischemia followed by 24 h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200 mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200 mg/kg. The 300 mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200 mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation.

Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports.

BACKGROUND: In the early literature, unintentional vitamin C deficiency in humans was associated with heart failure. Experimental vitamin C deficiency in guinea pigs caused enlargement of the heart. The purpose of this study was to collect and analyze case reports on vitamin C and pulmonary hypertension. METHODS: We searched Pubmed and Scopus for case studies in which vitamin C deficiency was considered to be the cause of pulmonary hypertension. We selected reports in which pulmonary hypertension was diagnosed by echocardiography or catheterization, for any age, sex, or dosage of vitamin C. We extracted quantitative data for our analysis. We used the mean pulmonary artery pressure (mPAP) as the outcome of primary interest. RESULTS: We identified 32 case reports, 21 of which were published in the last 5 years. Dyspnea was reported in 69%, edema in 53% and fatigue in 28% of the patients. Vitamin C plasma levels, measured in 27 cases, were undetectable in 24 and very low in 3 cases. Diet was poor in 30 cases and 17 cases had neuropsychiatric disorders. Right ventricular enlargement was reported in 24 cases. During periods of vitamin C deficiency, the median mPAP was 48 mmHg (range 29-77 mmHg; N = 28). After the start of vitamin C administration, the median mPAP was 20 mmHg (range 12-33 mmHg; N = 18). For the latter 18 cases, mPAP was 2.4-fold (median) higher during vitamin C deficiency. Pulmonary vascular resistance (PVR) during vitamin C deficiency was reported for 9 cases, ranging from 4.1 to 41 Wood units. PVR was 9-fold (median; N = 5) higher during vitamin C deficiency than during vitamin C administration. In 8 cases, there was direct evidence that the cases were pulmonary artery hypertension (PAH). Probably the majority of the remaining cases were also PAH. CONCLUSIONS: The cases analyzed in our study indicate that pulmonary hypertension can be one explanation for the reported heart failure of scurvy patients in the early literature. It would seem sensible to measure plasma vitamin C levels of patients with PH and examine the effects of vitamin C administration.