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ZusammenfassungHyperinflammation und oxidativer Stress spielen nicht nur bei akuter Covid-19-Erkrankung, sondern auch bei Long Covid eine wichtige pathophysiologische Rolle. Bei Covid-19 wurde ein Vitamin-C-Mangel nachgewiesen und der Benefit von supportiven Vitamin-C-Infusionen bereits untersucht. Bei Long Covid sind die überschießende Entzündung und reaktive Sauerstoffverbindungen ebenfalls Mitauslöser für Fibrosen, Thrombosen, Immun-Dysregulation (Autoimmunphänomene und Virenpersistenz), Fatigue, kognitive Beeinträchtigungen und Störungen des autonomen Nervensystems. Der Benefit von Vitamin-C-Infusionen – wie die Linderung von Fatigue, kognitiven Störungen und Schmerzen – ist bereits bei anderen Grunderkrankungen gut untersucht. Vitamin C ist eines der effektivsten Antioxidantien, Kofaktor relevanter Stoffwechselwege und ein wichtiger Immunmodulator. Der therapeutische Einsatz bei Long Covid ist deshalb sehr plausibel und wird durch praktische Erfahrung bestätigt.

ZusammenfassungEin Defizit an Vitamin C kann das Infektionsrisiko erhöhen. Begleitend bei einem grippalen Infekt eingesetzt, kann Vitamin C die Symptome bei ausreichend hoher Dosierung signifikant abmildern. Auch bei SARS-CoV-2-Infektionen zeigen Studien, dass supportives Vitamin C positive Wirkungen hat. Hochdosiertes intravenöses Vitamin C kann zudem Fatigue, kognitive Störungen und Schmerzen bei Erkrankungen, die mit oxidativem Stress einhergehen, reduzieren. Dass diese Effekte auch bei der Behandlung von Long-COVID-Betroffenen erzielt werden könnten, scheint plausibel.

ZusammenfassungWichtiges Anliegen der Palliativmedizin sind Linderung der Symptome und Verbesserung der Lebensqualität (QOL). Studien beobachten, dass sich die QOL von Patienten im letzten Lebensjahr noch nicht ausreichend verbessert hat. Häufig sind Beschwerden im Palliativbereich wie Schmerzen, Schwäche, Müdigkeit und Depression auch gleichzeitig bekannte Mangelsymptome bestimmter Vitamine. Es ist vorstellbar, dass Vitaminmangelsymptome im Symptomenkomplex Schwerstkranker möglicherweise unerkannt bleiben. Das Risiko für Vitaminmangelzustände ist im Palliativbereich nicht ausreichend untersucht. Im Rahmen einer Masterarbeit wurde die Vitaminversorgung exemplarisch bei 31 stationären Palliativpatienten untersucht. Alle Untersuchten in dieser Studiengruppe (75 % Krebs- und 25 % Nicht-Krebs-Patienten) wiesen defizitäre Konzentrationen von mindestens einem Vitamin auf, 68 % hatten gleichzeitig einen Mangel an mehreren Vitaminen. Dieser Unterversorgung sollte therapeutisch mehr Aufmerksamkeit geschenkt werden, denn die Behandlung von Mangelsymptomen ist kostengünstig und sehr gut verträglich. Der Fallbericht eines Patienten mit M. Parkinson und früher palliativmedizinischer Versorgung demonstriert die Umsetzungsmöglichkeiten in der Praxis.

ZusammenfassungAktuelle Studien zeigen einen deutlichen Benefit von Vitamin C bei COVID-19. Signifikante Verbesserungen gab es bei Sauerstoffversorgung, Reduktion des Zytokinsturms, Mortalitätsrisko, Heilungsrate und Verweildauer im Krankenhaus. Bei der supportiven Therapie mit Vitamin C erzielen Infusionen höhere Wirkspiegel im Blut als die orale Gabe, bei der u. a. genetisch bedingte Resorptionsunterschiede die Wirkung beeinflussen.

For glioblastoma, the treatment with standard of care therapy comprising resection, radiation, and temozolomide results in overall survival of approximately 14-18 months after initial diagnosis. Even though several new therapy approaches are under investigation, it is difficult to achieve life prolongation and/or improvement of patient's quality of life. The aggressiveness and progression of glioblastoma is initially orchestrated by the biological complexity of its genetic phenotype and ability to respond to cancer therapy via changing its molecular patterns, thereby developing resistance. Recent clinical studies of pharmacological ascorbate have demonstrated its safety and potential efficacy in different cancer entities regarding patient's quality of life and prolongation of survival. In this review article, the actual glioblastoma treatment possibilities are summarized, the evidence for pharmacological ascorbate in glioblastoma treatment is examined and questions are posed to identify current gaps of knowledge regarding accessibility of ascorbate to the tumor area. Experiments with glioblastoma cell lines and tumor xenografts have demonstrated that high‑dose ascorbate induces cytotoxicity and oxidative stress largely selectively in malignant cells compared to normal cells suggesting ascorbate as a potential therapeutic agent. Further investigations in larger cohorts and randomized placebo‑controlled trials should be performed to confirm these findings as well as to improve delivery strategies to the brain, through the inherent barriers and ultimately to the malignant cells.

Virale Infektionen fuhren zu einer uberschiesenden Immun- bzw. Entzundungsreaktion, die den Korper schadigt und die Abwehrlage reduziert. In der Folge steigt das Risiko fur lebensbedrohliche Pneumonien durch normalerweise harmlose Pneumokokken-Stamme. Aus diesem Grunde ist eine immunmodulierende, antientzundliche Therapie notwendig. Vitamin C ist ein wichtiger korpereigener Immunmodulator, der bei Infekten in hohem Mas verbraucht wird. Er aktiviert die Immunabwehr (z. B. Interferon, NK-Zellaktivitat) und schutzt gleichzeitig vor uberschiesenden Entzundungen (Reduktion von IL1, TNF-α). Vitamin-C-Infusionen beheben schnell Mangelsituationen und lindern Symptome, indem sie vor oxidativem Stress schutzen. Sie sind gut mit anderen naturheilkundlichen Therapien kombinierbar.

Objective The main purpose of palliative care is symptom relief. Frequently, the symptoms of patients requiring palliative care are the same as common symptoms of vitamin deficiency (e.g. pain, weakness, fatigue, depression). The study aim was to investigate whether patients in palliative care are vitamin deficient. Method This was a monocentre cross-sectional study. Patients attending the palliative care unit of a general hospital in Germany from October 2015 to April 2016 were examined for vitamin blood concentrations and symptoms. Data were analysed using univariate analysis and bivariate correlations. Results Data were available from 31 patients. Vitamin D3 deficiency (Conclusion All patients showed a deficiency in at least one of the measured vitamins; 68% had concurrent deficiencies in >1 vitamin. A follow-up study using validated questionnaires and a larger sample is needed to investigate the effects of targeted vitamin supplementation on quality of life and symptom burden.

ObjectiveOxidative stress appears to be a key factor in the pathogenesis of allergic diseases and a potential therapeutic target in allergy treatment. Allergic diseases are reportedly associated with reduced plasma levels of ascorbate, which is a key physiological antioxidant. Ascorbate prevents excessive inflammation without reducing the defensive capacity of the immune system.MethodsAn interim analysis of a multicenter, prospective, observational study was conducted to investigate the change in disease-specific and nonspecific symptoms (fatigue, sleep disorders, depression, and lack of mental concentration) during adjuvant treatment with intravenous vitamin C (Pascorbin®; Pascoe, Giessen, Germany) in 71 patients with allergy-related respiratory or cutaneous indications.ResultsBetween the start and end of treatment, the mean sum score of three disease-specific symptoms decreased significantly by 4.71 points and that of four nonspecific symptoms decreased significantly by 4.84 points. More than 50% of patients took no other allergy-related medication besides vitamin C.ConclusionsOur observations suggest that treatment with intravenous high-dose vitamin C reduces allergy-related symptoms. Our observations form a basis for planning a randomized controlled clinical trial to obtain more definitive evidence of the clinical relevance of our findings. We also obtained evidence of ascorbate deficiency in allergy-related diseases. Trial registration: Clinical Trials NCT02422901.

Objective Acute inflammation induced by administration of Escherichia coli lipopolysaccharide endotoxin (LPS) reduces plasma concentrations of vitamin C and impairs vascular endothelium-derived nitric oxide (NO) bioactivity. We tested the hypothesis that systemically administered high dose vitamin C restores the endogenous anti-oxidant potential and improves NO-dependent vasodilatation in the forearm vasculature. Design & setting 36 male subjects were enrolled in this balanced, placebo controlled cross-over study. Forearm blood flow (FBF) reactivity to acetylcholine (ACh) and glyceryl-trinitrate (GTN), a sensitive test for endothelial function, was assessed at baseline and 4 h after LPS-administration (20 IU/kg i.v). The effect of two different doses of intravenous vitamin C (Vitamin C-Injektopas®), 320 mg/kg and 480 mg/kg over 2 h, or placebo on forearm vascular function was studied after LPS. Main results LPS caused transient flu-like symptoms, decreased plasma vitamin C concentrations and reduced the ACh-dependent increase in FBF by up to 76%. Vitamin C at a mean plasma concentration of 3.2 or 4.9 mmol/L restored the response to ACh compared to baseline. Conclusion High dose systemic vitamin C recovers LPS-induced endothelium-dependent vasodilation in the forearm resistance vasculature. This provides a rationale for a further clinical study of the systemic vitamin C effect under inflammatory conditions.

Summary Background Vitamin C is an immune-relevant micronutrient, which is depleted in viral infections and this deficiency seems to play a critical role in the pathogenesis of herpes infections and in the development of postherpetic neuralgia. The objective of this observational multicenter study was to evaluate the utilization, safety and efficacy of intravenously administrated vitamin C in patients with shingles. Material/Methods Between April 2009 and December 2010 16 general practitioners recorded data of 67 participants with symptomatic herpes zoster who received vitamin C intravenously (Pascorbin® 7.5 g/50 ml) for approximately 2 weeks in addition to standard treatment. The assessment of pain (VAS) and the dermatologic symptoms of shingles such as hemorrhagic lesions and the number of efflorescences were investigated in a follow-up observation phase of up to 12 weeks. Results Mean declines of pain scores (VAS), number of affected dermatomes and efflorescences, and the presence of hemorrhagic vesicles between the baseline and follow-up assessments at 2 and 12 weeks were statistically significant. Overall, 6.4% of the participants experienced post-herpetic neuralgia. Common complaints such as general fatigue and impaired concentration also improved during the study. The effects and the tolerability of the treatment were evaluated positively by the physicians. The risk of developing PHN was reduced. Conclusions The data presented here provide evidence that concomitant use of intravenously administered ascorbic acid may have beneficial effects on herpes zoster-associated pain, dermatologic findings and accompanying common complaints. To confirm our findings, randomized, placebo-controlled clinical studies are necessary.

Purpose While the benefits of ascorbic acid (vitamin C, ascorbate) as an essential nutrient are well established, its effects on tumor cells and in tumor treatment are controversial. In particular, conflicting data exist whether ascorbate may increase the cytotoxic effects of antineoplastic drugs or may rather exert adverse effects on drug sensitivity during cancer treatment. Findings are further obscured regarding the distinction between ascorbate and dehydroascorbate (DHA). Thus, the purpose of this study was to evaluate and directly compare the cytotoxic efficacy of ascorbate compared to DHA, and to analyse if ascorbate at pharmacological concentrations affects the efficacy of antineoplastic agents in prostate carcinoma cells. Methods We directly compare the effects of ascorbate (supplied as ‘Pascorbin® solution for injection’) and DHA on tumor cell viability, and determine IC50 values for various cell lines. At concentrations well below the IC50, ascorbate effects on cell proliferation and cell cycle are analysed. We furthermore determine changes in cellular sensitivity towards various cytostatic drugs upon pre-treatment of cells with ascorbate. Results We demonstrate higher therapeutic efficacy of ascorbate over DHA in various cell lines, independent of cell line-specific differences in ascorbate sensitivity, and identify the extracellular generation of H2O2 as critical mechanism of ascorbate action. We furthermore show that, in addition to pro-apoptotic effects described previously, ascorbate treatment already at concentrations well below the IC50 exerts anti-proliferative effects on tumor cells. Those are based on interference with the cell cycle, namely by inducing a G0/G1 arrest. Pre-treatment of tumor cells with ascorbate leads to increased cellular sensitivity towards Docetaxel, Epirubicin, Irinotecan and 5-FU, but not towards Oxaliplatin and Vinorelbin. For Docetaxel and 5-FU, a linear correlation between this sensitizing effect and the ascorbate dosage is observed. Conclusions The redox-active form of vitamin C, ascorbate, shows therapeutic efficacy in tumor cells. These antitumor effects of ascorbate are mainly based on its extracellular action and, in addition to the induction of apoptosis, also include an anti-proliferative effect by inducing cell cycle arrest. Furthermore, ascorbate treatment specifically enhances the cytostatic potency of certain chemotherapeutics, which implicates therapeutic benefit during tumor treatment. Electronic supplementary material The online version of this article (doi:10.1007/s00280-010-1418-6) contains supplementary material, which is available to authorized users.

This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License.-- et al., [Significance]: It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. [Recent Advances]: The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. [Critical Issues]: Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. [Future Directions]: Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities., A.C. is the recipient of a research grant, SAF2013-43271-R, from the Spanish Ministry of Economy and Competitiveness. A.D. was supported by grants by the Federal Ministry of Education and Research to the Center of Thrombosis and Hemostasis Mainz (BMBF 01EO1003). R.S. is the recipient of a Senior Principal Research Fellowship of the National Health and Medical Research Council of Australia. Several authors of this review were supported by the European Cooperation in Science and Technology (COST Action BM1203/EU-ROS).

The aim of the study was to evaluate under praxis conditions the safety and efficacy of intravenous (i.v.) vitamin C administration in the first postoperative year of women with breast cancer.Epidemiological multicentre cohort study, including 15 gynaecologists and general practitioners representatively distributed in Germany. Data from 125 breast cancer patients in UICC stages IIa to IIIb were selected for the study. A total of 53 of these patients were treated with i.v. vitamin C (supplied as Pascorbin® 7.5 g) additional to standard tumour therapy for at least 4 weeks (study group) and 72 without this additional therapy (control group). Main outcome measures were efficacy in regard to outcome and severity of disease- or therapy-induced complaints during adjuvant chemo- and radiotherapy and aftercare.Comparison of control and study groups revealed that i.v. vitamin C administration resulted in a significant reduction of complaints induced by the disease and chemo-/radiotherapy, in particular of nausea, loss of appetite, fatigue, depression, sleep disorders, dizziness and haemorrhagic diathesis. After adjustment for age and baseline conditions (intensity score before adjuvant therapy, chemotherapy, radiotherapy), the overall intensity score of symptoms during adjuvant therapy and aftercare was nearly twice as high in the control group compared to the study group. No side-effects of the i.v. vitamin C administration were documented.Oxidative stress and vitamin C deficiency play an important role in the etiology of adverse effects of guideline-based adjuvant chemo-/radiotherapy. Restoring antioxidative capacity by complementary i.v. vitamin C administration helps to prevent or reduce disease-, or therapy-induced complaints in breast cancer patients.Complementary treatment of breast cancer patients with i.v. vitamin C was shown to be a well tolerated optimization of standard tumour-destructive therapies, reducing quality of life-related side-effects.

Lymphopenia commonly occurs in cancer patients and predicts poor prognosis. It is caused by radio- and chemotherapy, with malnutrition and treatment-related oxidative stress playing key roles in its pathogenesis. Tumour-related morbidity is reported to be associated with reduced plasma ascorbate, which is a key physiological antioxidant and essential factor in immune function. A prospective observational study was conducted on 48 cancer patients with lymphopenia (