Feasibility of Vitamin C in the Treatment of Post Viral Fatigue with Focus on Long COVID, Based on a Systematic Review of IV Vitamin C on Fatigue

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

Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C

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

Intravenous vitamin C in the treatment of allergies: an interim subgroup analysis of a long-term observational study

Objective Oxidative 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. Methods An 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. Results Between 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. Conclusions Our 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

Antioxidants in Translational Medicine

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. Antioxid. Redox Signal. 23, 1130–1143