Alteration of chemical behavior of L-ascorbic acid in combination with nickel sulfate at different pH solutions in vitro

Objective:To evaluate the alteration of chemical behavior of L-ascorbic acid(vitamin C) with metal ion(nickel) at different pH solutions in vitro.Methods:Spectra of pure aqueous solution of L-ascorbic acid(E mark) compound and NiSO_4(H_2O)(sigma USA) were evaluated by UV visible spectrophotometer.Spectral analysis of L-ascorbic acid and nickel at various pH(2.0, 7.0,7.4 and 8.6) at room temperature of 29℃ was recorded.In this special analysis,combined solution of L-ascorbic acid and nickel sulfate at different pH was also recorded.Results:The result revealed that λ_(max)(peak wavelength of spectra) of L-ascorbic acid at pH 2.0 was 289.0 run whereas at neutral pH 7.0,λ_(max) was 29S.4 run.In alkaline pH 8.6,λ_(max) was 295.4 nm and at pH 7.4 the λ_(max) of L-ascorbic acid remained the same as 295.4 nm.Nickel solution at acidic pH 2.0 was 394.5 nm,whereas at neutral pH 7.0 and pH 7.4 were the same as 394.5 nm.But at alkaline pH 8.6,λ_(max) value of nickel sulfate became 392.0 nm.The combined solution of L-ascorbic acid and nickel sulfate(6 mg/mL each) at pH 2.0 showed 292.5 nm and 392.5 nm,respectively whereas at pH 7.0,L-ascorbic acid showed 296.5 nm and nickel sulfate showed 391.5 nm.At pH 7.4,L-ascorbic acid showed 297.0 nm and nickel sulfate showed 394.0 nm in the combined solution whereas at pH 8.6(alkaline) L-ascorbic acid and nickel sulfate were showing 297.0 and 393.5 nm,respectively. Conclusions:Results clearly indicate an altered chemical behavior of L-ascorbic acid either alone or in combination with nickel sulfate in vitro at different pH.Perhaps oxidation of L-ascorbic acid to L-dehydro ascorbic acid via the free radical(HSc*) generation from the reaction of H,ASc + Ni(Ⅱ) is the cause of such alteration of λ_(max),value of L-ascorbic acid in the presence of metal nickel.

Hydrocortisone, ascorbic acid and thiamine for sepsis: Is the jury out?

Sepsis and septic shock remain a major cause of morbidity and mortality among patients admitted in the intensive care unit.Diabetes is a major risk factor for the development of sepsis.The global mortality of sepsis remains high,despite significant interventions and guidelines.It has been known for decades that patients with sepsis have reduced levels of antioxidants,most notably vitamin C.Furthermore,experimental data has demonstrated multiple beneficial effects of vitamin C in sepsis.In addition,corticosteroids and thiamine may have synergistic biological effects together with vitamin C.Preliminary data suggests that therapy with hydrocortisone,ascorbic acid and thiamine improves the outcome of patients with sepsis with the potential to save millions of lives.However,this intervention has met with much resistance and has not been widely adopted.Ultimately,we await the final jury verdict on this simple,safe and cheap intervention.

A critical role of gastric mucosal ascorbic acid in the progression of acute gastric mucosal lesions induced by compound 48/80 in rats

AIM: To study the role of gastric mucosal ascorbic acid(AA) in the progression of acute gastric mucosal lesions induced by compound 48/80 (C48/80), a mast cell degranulator, in rats.METHODS: C48/80 (0.75 mg/kg) was intraperitoneally injected to fasted Wistar rats. Oral administration of AA (10, 50 or 100 mg/kg) was performed 0.5 h after C48/80treatment. Determinations for gastric mucosal lesion severity and blood flow, and assays for gastric mucosal total AA, reduced AA, oxidized AA, vitamin E, thiobarbituric acid reactive substances (TBARS), adherent mucus, nitrite/nitrate (NOx), non-protein SH (NPSH), and myeloperoxidase(MPO), and serum total AA, reduced AA, oxidized AA,and NOx were conducted 0.5 and 3 h after C48/80treatment.RESULTS: Gastric mucosal lesions occurred 0.5 h after C48/80 treatment and progressed at 3 h. Gastric mucosal blood flow decreased 0.5 h after C48/80 treatment but the decrease was recovered at 3 h. Gastric mucosal total AA, reduced AA, vitamin E, and adherent mucus concentrations decreased 3 h after C48/80 treatment.Gastric mucosal oxidized AA concentration remained unchanged after C48/80 treatment. Gastric mucosal NPSH concentration decreased 0.5 h after C48/80 treatment,but the decrease was recovered at 3 h. Gastric mucosal TBARS concentration and MPO activity increased 0.5 h after C48/80 treatment and further increased at 3 h.Serum total AA and reduced AA concentrations increased 0.5 h after C48/80 treatment and further increased at 3 h, while serum oxidized AA concentration increased at 0.5 h. Serum and gastric mucosal NOx concentrations increased 3 h after C48/80 treatment. AA administration to C48/80-treated rats at 0.5 h after the treatment prevented the gastric mucosal lesion progression and the changes in gastric mucosal total AA, reduced AA, vitamin E, adherent mucus, NOx, and TBARS concentrations and MPO activity and serum NOx concentration found at 3 h after the treatment dose-dependently. The AA administration to C48/80-treated rats caused further increases in serum total AA and reduced AA concentrations at 3 h after the treatment dose-dependently.CONCLUSION: Gastric mucosal AA plays a critical role in the progression of C48/80-induced acute gastric mucosal lesions in rats.

Role of vitamin C in diabetic ketoacidosis:Is it ready for prime time?

Diabetic ketoacidosis(DKA) is life-threatening acute metabolic complication of diabetes mellitus(DM) that is characterized by acidosis, ketosis, and hyperglycemia, currently affecting mostly patients under 30 years of age with diabetes mellitus type 1. In both, DM and DKA, a pro-inflammatory state exists. This clinical entity occurs as a result of hyperglycemia-induced disturbances, resulting in an increased oxidative metabolism. For the latter reason, the use of vitamin C seems promising in DKA due to its antioxidant role in reducing the superoxide radicals that are consequence of the oxidative stress. This can decrease the proinflammatory state and avoids complications. Vitamin C, or also known as ascorbic acid, has been widely used in several illnesses, such as common cold, tissue healing, fertility, atherosclerosis, cancer prevention, immunity restoration, neuro-degenerative disease and also has been suggested to decrease the risk of DM, and this reason is giving place to believe that vitamin C can have an important role in treating diabetic complications such as DKA. In order to counteract these oxidative disturbances in DKA patients, we analyzed the current data regarding vitamin C and evaluate its role in any type treatment of this complication in the near future.

植物果实中维生素C合成代谢及其基因表达研究

维生素C(Vitamin C),又名抗坏血酸(Ascorbate acid,AsA),是生物体中具有多效功能的必需化合物。整理了植物果实中维生素C的生理功能以及其中参与维生素C合成的L-半乳糖途径、D-半乳糖醛酸途径、L-古洛糖途径、肌醇途径和维生素C循环途径,并分析了相关基因的功能和表达。对参与维生素C合成与循环的16个基因:PMI、PMM、GMP、GME、GGP、GPP、GalDH、GLDH、GalUR、MIOX、GuLDH、MDHAR、DHAR、AO、APX、GR,及其在维生素C代谢途径中的作用进行了综述。植物果实中维生素C合成代谢途径多样,关键基因的表达会在不同程度上影响其合成代谢,了解植物果实中维生素C合成代谢及相关基因的功能和表达,可为生产富含维生素C的转基因水果和蔬菜奠定基础。

维生素C在老年肌少症中的作用机制及防治潜力

背景:维生素C作为人体所必需的营养物质,具有广泛的生物学效应并存在多种与肌少症发病机制相关的生物学功能,研究维生素C的补充应用有望成为肌少症的一种新型防治措施。目的:综述近年来有关维生素C在肌少症发病机制和治疗中应用的最新研究进展,并基于已发表的证据探讨维生素C在肌少症预防和治疗中的潜在作用及可能的机制途径。方法:由第一作者应用计算机在PubMed、Web of Science和中国知网数据库检索涉及维生素C在肌少症中的相关文献。英文检索词:“vitamin C,ascorbic acid,L-ascorbic acid,ascorbate,antioxidants,oxidative stress,sarcopenia,muscular atrophy,muscle weakness,muscle development,skeletal muscle regenerate,muscles,skeletal muscle”;中文检索词:“维生素C,抗坏血酸,L-抗坏血酸,抗坏血酸盐,抗氧化剂,氧化应激,肌少症,肌肉萎缩,肌肉无力,肌肉发育,骨骼肌再生,肌肉,骨骼肌”。检索时限为各数据库建库至2023年7月,经过筛选后纳入85篇文献进行综述分析。结果与结论:①保证充足的膳食维生素C摄入或维持血液循环中正常的维生素C水平将有助于减少与年龄相关的肌肉损失,降低肌少症的患病率,此外,补充维生素C对于改善骨骼肌肌肉质量、力量和躯体功能也有一定作用,并可能在肌少症患者的运动策略中发挥协同效应。②维生素C对肌少症的作用可能经由以下生物学机制:维生素C主要通过抑制骨骼肌氧化应激和炎症反应来限制泛素-蛋白酶体途径的激活,从而积极调控蛋白质代谢稳态,并可通过其抗氧化作用增强线粒体抗氧化防御能力,维持线粒体的健康功能。另外,维生素C可以影响肌细胞增殖、分化和肌管大小,主要通过增加生肌调节因子的表达和激活蛋白质合成信号通路来实现,这有助于促进肌肉发育以及修复和再生受损的肌肉组织。③对于维生素C干预肌少症所发挥的积极作用尚需开展大样本及对一些重要影响因素进行优化设计的研究,如补充剂量和补充时间的选择、维生素C联合运动干预时的运动处方设计以及对个体的氧化还原状态评估等,建议未来的研究应以维生素C状态不佳的老年肌少症患者(<50μmol/L)为研究对象,探讨长期补充1000 mg/d维生素C(6个月或更长时间)与至少两种以上多类型综合运动的联合干预效果,补充时间选择在运动结束后的1 h进行,并对运动期间产生的氧化损伤标志物如丙二醛或蛋白质羟基水平进行监测。总之,对于肌少症老年人最佳的维生素C补充剂量和时间选择还需更多探讨,同时合适的运动处方设计(特别是运动类型和强度)亦需要进一步研究确定。

Vitamin C activation of the biosynthesis of epoxyeicosatrienoic acids

The cardiovascular effects of vitamin C (VitC) could be mediated by epoxyeicosatrienoic acids (EETs). We aimed to study the mechanism of VitC-dependent microsomal formation of cis- and trans-EETs and the regulation of EET levels in rat isolated perfused kidneys and in vivo. VitC biphasically stimulated rat kidney microsomal cis- and trans-EET formation in a ratio of 1:2, involving the participation of lipid hydroperoxides (LOOHs), Fe2+ , and cytochrome P450 (CYP). Levels of LOOHs correlated with microsomal EET production. LOOH stimulation of CYP isoforms resulted in preferred trans- over cis-EET formation from arachidonic acid and was associated with the cleavage of LOOHs, which indicated a CYP peroxy-genase activity. EETs contributed to VitC-induced vasodilator responses in rat isolated perfused kidneys. VitC (1 mg/ml) given in the drinking water for 9 days doubled rat urinary EET excretion, increased plasma levels of EETs, mostly trans-EETs, by 40%, and reduced plasma levels of 20-hydroxyeicosatetraenoic acid. Depletion of VitC in brain cortex and kidney tissues by more than 20- and 50-fold, respectively, in gulonolactone oxidase-knockout mice was associated with mild increases in tissue EETs. These data suggest that LOOHs are a determinant factor for EET formation in vivo in which VitC exerts a key regulatory effect. VitC-activated CYP peroxygenase activity may represent a CYP interaction with lipoxygenases and cyclooxygenases to mediate the cardiovascular effects of VitC via formation of EETs.

库仑滴定法测定Vitamin C片及黄瓜、青椒中抗坏血酸的含量

建立了以1.0 mol.L-1碘化钾和1.0 mol.L-1醋酸混合液作为电解液的恒电流库仑滴定法测定抗坏血酸含量的方法。结果表明,方法的回收率在98.3%~100.8%之间,RSD在0.21%~0.56%(n=3)。该法可直接用于V itam in C片及黄瓜、青椒等样品中抗坏血酸含量的测定,方法简便灵敏,结果令人满意。

维生素C含量测定本科教学实验设计与实践

在仪器分析实验教学中,以“当被测物质具有酸性或碱性基团时,溶剂的p H值对光谱影响较大”知识为实验的切入点,由低年级本科生来探索研究维生素C在中性和不同浓度的酸性介质环境中紫外吸收光谱特性和稳定性,建立用紫外吸收分光光度法稳定、快速测定维生素C含量的方法。通过合理的教学实验设计,将理论与实验教学相融合,使理论知识点在实验中可视化,直观且容易理解,提高了学生的学习热情,锻炼了本科生理论知识联系实际运用能力。

Preventive and Therapeutic Potential of Vitamin C in Mental Disorders

In this review,we summarize the involvement of vitamin C in mental disorders by presenting available evidence on its pharmacological effects in animal models as well as in clinical studies.Vitamin C,especially its reduced form,has gained interest for its multiple functions in various tissues and organs,including central nervous system（CNS）.Vitamin C protects the neuron against oxidative stress,alleviates inflammation,regulates the neurotransmission,affects neuronal development and controls epigenetic function.All of these processes are closely associated with psychopathology.In the past few decades,scientists have revealed that the deficiency of vitamin C may lead to motor deficit,cognitive impairment and aberrant behaviors,whereas supplement of vitamin C has a potential preventive and therapeutic effect on mental illness,such as major depressive disorder（MDD）,schizophrenia,anxiety and Alzheimer＇s disease（AD）.Although several studies support a possible role of vitamin C against mental disorders,more researches are essential to accelerate the knowledge and investigate the mechanism in this field.

Vitamin C in the critically ill-indications and controversies

Ascorbic acid(vitamin C) elicits pleiotropic effects in thebody. Among its functions, it serves as a potent antioxidant, a co-factor in collagen and catecholamine synthesis, and a modulator of immune cell biology. Furthermore, an increasing body of evidence suggests that highdose vitamin C administration improves hemodynamics, end-organ function, and may improve survival in critically ill patients. This article reviews studies that evaluate vitamin C in pre-clinical models and clinical trials with respect to its therapeutic potential.

Development of a Freeze-Dried Skin Care Product Composed of Hyaluronic Acid and Poly(γ-Glutamic Acid) Containing Bioactive Components for Application after Chemical Peels

Eight types of spongy sheet were prepared by freeze-drying aqueous solutions of hyaluronic acid (HA) and poly(γ-glutamic acid) (PGA) with or without bioactive components including vitamin C derivative (VC), glucosylceramide (GC), and epidermal growth factor (EGF). Spongy sheets were categorized into the following groups: Group I (HA/PGA), Group II (HA/PGA + VC), Group III (HA/PGA + GC), Group IV (HA/PGA + VC, GC), Group V (HA/PGA + EGF), Group VI (HA/PGA + VC, EGF), Group VII (HA/PGA + GC, EGF), and Group VIII (HA/PGA + VC, GC, EGF). In the first experiment, we examined fibroblast proliferation in conditioned medium that had been prepared by immersing each spongy sheet in a conventional culture medium. EGF-incorporating spongy sheets (Groups V-VIII) enhanced fibroblast proliferation more than EGF-free spongy sheets (Groups I-IV). In the second experiment, cytokine production by fibroblasts was evaluated using a wound surface model. This involved elevation of fibroblasts-incorporating collagen gel sheets to the air-liquid interface, on which a spongy sheet (Groups I, IV, V and VIII) was placed and cultured for 1 week. EGF-incorporating spongy sheets (Groups V and VIII) enhanced the production of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by fibroblasts more than EGF-free spongy sheets (Groups I and IV). The effect of these four types of spongy sheet on wounds was investigated in animal experiments. Chemical peel was performed by contacting 50% trichloroacetic acid (TCA) on the dorsal region of mice, after which a spongy sheet was placed, and the wound condition was then observed in a two-week period. Angiogenesis was facilitated to a greater degree in Group VIII compared with Groups I, IV and V. This finding indicates that Group VIII spongy sheet is a promising aid for skin recovery after chemical peel.

Current role of high dose vitamin C in sepsis management:A concise review

Sepsis and septic shock are common diagnoses for patients requiring intensive care unit admission and associated with high morbidity and mortality.In addition to aggressive fluid resuscitation and antibiotic therapy,several other drugs have been tried as adjuvant therapies to reduce the inflammatory response and improve outcomes.Vitamin C has been shown to have several biological actions,including anti-inflammatory and immunomodulatory effects,which may prove beneficial in sepsis management.Initial trials showed improved patient outcomes when high dose vitamin C was used in combination with thiamine and hydrocortisone.These results,along with relative safety of high-dose(supra-physiological)vitamin C,encouraged physicians across the globe to add vitamin C as an adjuvant therapy in the management of sepsis.However,subsequent largescale randomised control trials could not replicate these results,leaving the world divided regarding the role of vitamin C in sepsis management.Here,we discuss the rationale,safety profile,and the current clinical evidence for the use of highdose vitamin C in the management of sepsis and septic shock.

维生素C在呼吸道感染中应用的研究进展

近年来,维生素C在呼吸道感染等疾病的辅助治疗中被广泛应用,但其有效性却备受质疑。本文探讨了维生素C对呼吸系统感染性疾病的影响,查阅相关文献梳理了其作用机制、给药剂量以及不良反应。数十年来,大量研究证实,维生素C通过减弱氧化应激、降低炎性反应、调节免疫、改善循环、抗病原微生物、保护肺脏等作用,对呼吸道感染性疾病预防及治疗具有一定影响。有研究表明,应用维生素C对疾病治疗可能无明显效果。年龄、体质量、性别等因素均可能影响维生素C的需求量。自维生素C问世以来,大量动物模型实验及临床研究报道了其在感染性疾病中的有效性,且具有安全性较高、价格低廉、百姓熟知等特点,不应否定维生素C的临床价值。

Effects of Simulated Acid Rain on Main Nutritional Indicators of Three Leafy Vegetables

The purpose of this paper was to identify content changes in the main nutritional indicators of three common leafy vegetables, and to provide a theoretical basis for the protection of leafy vegetables from acid rain. The experiment investigated the effects of simulated acid rain on four main nutritional indicators, including soluble sugar, total free amino acid, soluble protein and vitamin C during the application of simulated acid rain(SAR) in pakchoi(Brassica rapa chinensis), rape(Brassica campestris L.) and lettuce(Lactuca sativa Linn. var. ramosa Hort). The vegetables were respectively exposed to SAR of pH=7.0, 5.6, 5.0, 4.0, 3.0 and a control level of pH=6.5. The concentrations of the four main nutritional indicators were determined at harvest. The results show that nutritional quality of the three leafy vegetable species decreased with the declining of pH values of SAR. The higher the acidity of SAR was, the more significant the inhibitions were. Nutritional quality of lettuce was the most affected by simulated acid rain, followed by pakchoi and rape. The change range of soluble protein content was higher than those of the other three indicators’ contents, which indicates that soluble protein is most sensitive to simulated acid rain.

Vitamin C twice a day enhances health

This review provides information determining how much vitamin C to take, including analysis of the recent findings, which demonstrate advantages and problems with higher daily doses. The Daily Value for vitamin C was raised to 90 mg for men in 2000, and Upper Limit of 2,000 mg per day was established as being safe. This followed a study of urinary excretion of vitamin C (AA) that demonstrated 500 mg twice a day provides levels sufficient to cause continuous urinary excretion in humans. That is the lowest oral dosage evaluated that significantly saturates blood plasma. A later study endorsed 200 mg from dietary sources for the RDA. Even though plasma concentration of AA is then significantly lower, at 200 mg daily certain white blood cells are saturated with AA. Recently many studies have indicated the benefit of high levels of AA to maintain the brain, bones, and heart, reduce damage from stroke, brain trauma, and cataracts, and lower the risk of cancer metastasis and colds. Pro-oxidant activity has been found only for i.v. adminstration, where high concentrations appear effective destroying tumor cells while not harming normal cells. This review evaluates recent research and finds it consistent with the hypothesis that people, especially older people and soldiers in combat environments, are likely to benefit if they maintain the saturating level of AA by taking 500mg supplements twice a day.

维生素C的功能及其在奶牛养殖中的应用

维生素C作为重要的抗氧化剂,对于缓解机体氧化应激提升免疫力有着重要意义。而奶牛因可通过肝脏内源性合成,导致其重要性多年来一直被低估。随着奶牛生产水平的提升,有研究表明在热应激、肝脏受损、疾病和分娩时会导致体内的维生素C水平降低,而通过外源性补充维生素C可改善奶牛生产性能。因此本文对目前关于维生素C的理化性质、生物功能及其在奶牛领域的应用做简要综述,为进一步探究维生素C对奶牛健康及繁殖的影响奠定理论基础。

Is Titration as Accurate as HPLC for Determination of Vitamin C in Supplements? <br/>—Titration versus HPLC for Vitamin C Analysis

Herein, the iodometric titration and HPLC-RP methods were compared for the determination of vitamin C in vitamin and mineral supplements. The methods were validated in terms of linearity, limits of detection (LOD), limits of quantification (LOQ), precision, and recovery by using vitamin standards and a reference material SRM 3280 (multivitamin/multimineral tablets) obtained from the National Institute of Standards and Technology (NIST). A total of 22 samples of vitamin supplements, randomly acquired in local markets of Sao Paulo (Brazil) were evaluated for content of vitamin C by these two methodologies. The precision expressed as RSD was lower than 5% for both methods. LOD was 3.6 μg/mL for HPLC and 1.0 mg for titration, while LOQ were 12.0 μg/mL and 3.0 mg for HPLC and titration, respectively. Percent recoveries (%) of spiked samples ranged from 98.7 to 100.5 for HPLC and from 98 to 104 for titration. The contents of vitamin C in SRM 3280 (Certified value = 42.2 ± 3.7 mg/g) were 40.2 and 42.1 mg/g when determined by HPLC and titration respectively. Statistically, there was no difference in the analysed vitamin C content for half of the samples, irrespective of the method applied. HPLC was more sensitive, but the titrimetric method was faster and consumed less reagent. Although both methods were accurate in determining the vitamin C content in SRM 3280, the matrix constituents of some vitamin supplements may have interfered with the analysis.

Adjuvant Administration of Vitamin C Improves Mortality of Patients with Sepsis and Septic Shock: A Systems Review and Meta-Analysis

The aim of this study was to examine whether vitamin C reduced mortality when adjutant therapy of patients with septic shock and severe sepsis compared with placebo by meta-analysis. Eligible trials were identified from Pubmed, Embase, Ovid, and the Cochrane database. Four randomized controlled trials (RCT) and two retrospective studies were published between 2000 and 2017 met the inclusion criteria and suitable for meta-analysis. The data were analyzed with randomized-effects or fixed-effects models using Review Manager Version 5.3. Four randomized studies with a total of 109 participants were suitable for meta-analysis. The heterogeneity was assessed by calculating the Q and I2 methods. A random-effects approach instead of a fixed-effects analysis was undertaken if I2 > 50%. Adjuvant vitamin C did not associate with a reduction in mortality as compared with placebo, it is occurred similarly in both RCT studies and retrospective studies. However, high doses of vitamin C (>50 mg/kg/day) significant reduced the mortality rate of severe sepsis patients. And administration of high doses of vitamin C to therapy severe sepsis did not significantly reduce the ICU length of stay. The results suggested a trend toward reducing mortality in severe sepsis and septic shock patients’ adjuvant with vitamin C. Further multicenter large randomized controlled trials are necessary to determine the potential benefits of vitamin C in patients with severe sepsis and septic shock.

Role of high dose vitamin C in management of hospitalised COVID-19 patients:A minireview

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has emerged as one of the most dreadful viruses the mankind has witnessed.It has caused worldwide havoc and wrecked human life.In our quest to find therapeutic options to counter this threat,several drugs have been tried,with varying success.Certain agents like corticosteroids,some anti-virals and immunosuppressive drugs have been found useful in improving clinical outcomes.Vitamin C,a water-soluble vitamin with good safety profile,has been tried to reduce progression and improve outcomes of patients with coronavirus disease 2019(COVID-19).Because of its anti-oxidant and immunomodulatory properties,the role of vitamin C has expanded well beyond the management of scurvy and it is increasingly been employed in the treatment of critically ill patients with sepsis,septic shock,acute pancreatitis and even cancer.However,in spite of many case series,observational studies and even randomised control trials,the role of vitamin C remains ambiguous.In this review,we will be discussing the scientific rationale and the current clinical evidence for using high dose vitamin C in the management of COVID-19 patients.