Oxidative stress is a pivotal point in the pathophysiology of COVID-19 and presumably also in Long-COVID. Inflammation and oxidative stress are mutually reinforcing each other, thus contributing to the systemic hyperinflammatory state and coagulopathy which are cardinal pathological mechanisms of severe stages. COVID-19 patients, like other critically ill patients e.g. with pneumonia, very often show severe deficiency of the antioxidant vitamin C. So far, it has not been investigated how long this deficiency lasts or whether patients with long COVID symptoms also suffer from deficiencies. A vitamin C deficit has serious pathological consequences because vitamin C is one of the most effective antioxidants, but also co-factor of many enzymatic processes that affect the immune and nervous system, blood circulation and energy metabolism. Because of its anti-oxidative, anti-inflammatory, endothelial-restoring, and immunomodulatory effects the supportive intravenous (iv) use of supraphysiological doses has been investigated so far in 12 controlled or observational studies with altogether 1578 inpatients with COVID-19. In these studies an improved oxygenation, a decrease in inflammatory markers and a faster recovery were observed. In addition, early treatment with iv high dose vitamin C seems to reduce the risks of severe courses of the disease such as pneumonia and also mortality. Persistent inflammation, thrombosis and a dysregulated immune response (auto-immune phenomena and/or persistent viral load) seem to be major contributors to Long-COVID. Oxidative stress and inflammation are involved in the development and progression of fatigue and neuro-psychiatric symptoms in various diseases by disrupting tissue (e.g. autoantibodies), blood flow (e.g. immune thrombosis) and neurotransmitter metabolism (e.g. excitotoxicity). In oncological diseases, other viral infections and autoimmune diseases, which are often associated with fatigue, cognitive disorders, pain and depression similar to Long-COVID, iv high dose vitamin C was shown to significantly relieve these symptoms. Supportive iv vitamin C in acute COVID-19 might therefore reduce the risk of severe courses and also the development of Long-COVID.

Fatigue is common not only in cancer patients but also after viral and other infections. Effective treatment options are still very rare. Therefore, the present knowledge on the pathophysiology of fatigue and the potential positive impact of treatment with vitamin C is illustrated. Additionally, the effectiveness of high-dose IV vitamin C in fatigue resulting from various diseases was assessed by a systematic literature review in order to assess the feasibility of vitamin C in post-viral, especially in long COVID, fatigue. Nine clinical studies with 720 participants were identified. Three of the four controlled trials observed a significant decrease in fatigue scores in the vitamin C group compared to the control group. Four of the five observational or before-and-after studies observed a significant reduction in pre–post levels of fatigue. Attendant symptoms of fatigue such as sleep disturbances, lack of concentration, depression, and pain were also frequently alleviated. Oxidative stress, inflammation, and circulatory disorders, which are important contributors to fatigue, are also discussed in long COVID fatigue. Thus, the antioxidant, anti-inflammatory, endothelial-restoring, and immunomodulatory effects of high-dose IV vitamin C might be a suitable treatment option.

In paediatrics, clinical study data are limited, especially on herbal medicinal products. To address this gap, 2063 datasets from the paediatric population were evaluated in the PhytoVIS data base. By screening for paediatric data, information on indication, gender, treatment, co-medication and tolerability were evaluated. The majority of patients was treated because of common cold, fever, digestive complaints, skin diseases, sleep disturbances and anxiety. The perceived effect of the therapy was rated in 84% of the patients as very good or good without adverse events. The data shed light on a still neglected field of phyto-pharmacotherapy by giving information on the use of herbal medicines in an unselected cohort of paediatric patients. The results confirm the good clinical effects and safety of herbal medicinal products in this patient population and show that they are widely used in Germany. What is Known:• In Germany, about 85% of children receive one or more herbal medicinal products per year.• Despite international initiatives to promote clinical research in paediatrics, there are still many gaps of knowledge in the use of drugs in paediatrics. What is New:• The PhytoVIS project evaluated 2063 data sets from the paediatric population using herbal medicinal products.• The majority of patients was treated because of common cold, fever, digestive complaints, skin diseases, sleep disturbances and anxiety, and 84% of the patients rated the therapy as very good or good without adverse events.

Einleitung Seit Inkrafttreten der Verordnung (EG) Nr. 1901/2006 im Jahr 2006, mit der die Entwicklung und Verfügbarkeit von Arzneimitteln für Kinder erleichtert werden soll, ist bis heute in einigen Bereichen zwar ein deutlicher Fortschritt erzielt worden, allerdings nicht bei den pflanzlichen Arzneimitteln (HMP). Methodik Im Mai 2022 wurde deshalb von der Stiftung „Plants for Health“, der Gesellschaft für Arzneipflanzen- und Naturstoff-Forschung (GA) und der Gesellschaft für Phytotherapie (GPT) ein internationales eSymposium mit Experten aus verschiedenen Fachgebieten organisiert, um geeignete Maßnahmen zur Etablierung von rational begründeten Dosierungsschemata für Phytotherapeutika zur Anwendung bei Kindern zu diskutieren. Dafür sollten der Status quo aus akademischer und klinisch-pädiatrischer Sicht dargestellt und verschiedene Besonderheiten einschließlich regulatorischer Anforderungen aus den deutschsprachigen Ländern, Großbritannien, Spanien und der Eurasischen Wirtschaftsunion analysiert werden. Als mögliche Lösungsansätze wurden klinische Studien, validierte Extrapolationsverfahren und die Generierung von Real-World-Daten (RWD) vorgestellt. Ergebnisse und Diskussion Die Anforderungen der Verordnung (EG) Nr. 1901/2006 werden aus phytotherapeutischer Sicht bislang nicht erfüllt. HMPs sind wirksame und sichere Therapieoptionen, die physiologischen Besonderheiten des Kindesalters erfordern jedoch eine Anpassung von Dosierungen und Zubereitungsformen. Registrierung, Inverkehrbringen und Anwendung von HMPs unterscheiden sich in verschiedenen europäischen Ländern bzw. Regionen teilweise erheblich. Für die Festlegung rational begründeter pädiatrischer Dosierungen für HMPs können unter bestimmten Prämissen die Extrapolation von entsprechenden Daten für Erwachsene sowie Daten aus den – derzeit allerdings nur wenigen – pädiatrischen klinischen Studien genutzt werden. RWD aus verschiedenen Quellen könnten ebenfalls zur Lösung der Probleme beitragen, allerdings erfordert dies eine Anpassung des bisherigen Rechtsrahmens. Introduction Since Regulation (EC) No. 1901/2006 came into force in 2006 to facilitate the development and availability of medicines for children, significant progress has been made in some areas to date, but not in herbal medicinal products (HMPs). Methods Therefore, in May 2022, an international eSymposium was organized by the Plants for Health Foundation, the Society for Medicinal Plant and Natural Product Research, and the German Society for Phytotherapy with experts from various disciplines to discuss appropriate measures for establishing rationally based dosing regimens for phytotherapeutics for use in children. For this purpose, the status quo from an academic and clinical-pediatric point of view was presented and various specific issues including the relevant regulatory requirements from German-speaking countries, the United Kingdom, Spain, and the Eurasian Economic Union were analyzed. Clinical trials, validated extrapolation protocols, and also real-world data (RWD) generation were discussed as appropriate solutions of the problem. Results and Discussion The requirements of Regulation (EC) No. 1901/2006 are not fulfilled from a phytotherapeutic point of view so far. HMPs are effective and safe therapeutic options, but the physiological characteristics of childhood require adaptation of the respective dosages and preparation forms. Registration, marketing and use of HMPs differ in different European countries and regions, sometimes considerably. For the establishment of rationally based pediatric dosages for HMPs, extrapolation of corresponding data for adults as well as data from the few pediatric clinical trials can be used under certain premises. RWD from a variety of sources could also help to address the issues, but this will require adaptation of the current regulatory framework. Article published online: 07 June 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

CBD-haltige Produkte wie sogenannte CBD-Öle werden in Form von Nahrungsmitteln und Nahrungsergänzungsmitteln vertrieben und vielfach mit medizinischen Indikationen bei schweren Erkrankungen beworben. Derzeit werden auf europäischer Ebene Anträge auf Novel-Food-Status bearbeitet. Bei genauerer Betrachtung erweisen sich jedoch bereits die Grundlagen für die Einstufung von CBD als Lebensmittel als fragwürdig. CBD ist eindeutig ein verschreibungspflichtiger Arzneistoff mit bekannten pharmakologischen Effekten, der im Falle von Cannabisextrakten zudem Betäubungsmittelstatus hat. Für die Verwendung in Nahrungsmitteln fehlen die lebensmitteltypischen Eigenschaften. Auch wenn CBD selbst in hohen Dosen toxikologisch unbedenklich ist: Durch eine nachgewiesene Anwendungssicherheit wird ein Arzneistoff nicht zum Lebensmittel. Is cannabidiol food or medicine? A positioning Products containing cannabidiol (CBD) such as CBD oil are marketed in the form of food or dietary supplements. They are often advertised with medical indications for serious illnesses. Applications for Novel Food Status are currently processed at European level. On closer examination, however, the basis for classifying CBD as a foodstuff is questionable. CBD is not only clearly a prescription drug with known pharmacological effects, derived from cannabis extracts, it even has a narcotic status. On the other hand, CBD lacks the food-typical properties to be used in / as food. Even if CBD seems to be toxicologically harmless even in high doses, this does not imply that a drug qualifies to be categorized as novel food just because it has been proven to be safe for consumers. Publication Date: 13 April 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany