Vitamin C, also known as ascorbic acid, is an essential water-soluble nutrient. Humans and a few other animals, such as primates, pigs, depend on vitamin C from the nutritional supply by fruits and vegetables (red peppers, oranges, strawberries, broccoli, mangoes, lemons). The potential role of vitamin C in preventing and ameliorating infection is well established in medical science.
Ascorbic acid is crucial for immune responses. It has important anti-inflammatory, immunomodulating, antioxidant, antithrombotic, and antiviral properties.
Vitamin C appears to favorably modulate host responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19) pandemic, especially in the critical stages. In a recent review published in Preprints*, Patrick Holford et al. address vitamin C's role as adjunctive therapy for respiratory infection, sepsis, and COVID-19.
This paper discusses the potential role of vitamin C in preventing the critical phase of COVID-19, acute respiratory infections, and other inflammatory diseases. Vitamin C supplementation could hold promise as a preventive or therapeutic agent for COVID-19 - to correct a disease-induced deficiency, reduce oxidative stress, enhance interferon production, and support the anti-inflammatory actions of glucocorticosteroids.
To maintain a normal plasma level of 50 µmol/l in adults, a vitamin C dose of 90 mg/d for men and 80 mg/d for women is required. This is enough to prevent scurvy (a disease resulting from a lack of vitamin C). However, this level is inadequate for preventing viral exposure and physiological stress.
Therefore, the Swiss Society of Nutrition recommends a supplement of 200mg of vitamin C for everyone - ‘to fill the nutrient gap for the general population and especially for the adults aged 65 and older. This supplement is targeted to strengthen the immune system.’
Vitamin C and immune response
A rapid decline in the human serum vitamin C levels is observed under conditions of physiological stress. A serum level of vitamin C ≤11 µmol/l is found in hospitalized patients - the majority of them suffering from acute respiratory infections, sepsis, or severe COVID-19.
Various case studies reported from across the world demonstrate that low vitamin C levels are typical in critically- ill hospitalized patients, with both respiratory infections, pneumonia, sepsis, and COVID-19 - the most likely explanation being increased metabolic consumption.
A meta-analysis highlights these observations: 1) risk of pneumonia is significantly reduced with vitamin C supplementation, 2) post-mortem investigations in COVID-19 deaths show a secondary pneumonia phenomenon, and 3) total pneumonia cohorts comprised 62% with hypovitaminosis C.
Mechanism of action of vitamin C
Vitamin C has an important homeostatic role as an antioxidant. It is known to demonstrate direct virucidal activity and augment interferon production. It has effector mechanisms in both the innate and adaptive immune systems. Vitamin C lessens reactive oxidative species (ROS) and inflammation via attenuation of NF-κB activation.
While SARS-CoV-2 downregulates the expression of type-1 interferons (the host's primary antiviral defense mechanism), ascorbic acid upregulates these key host defense proteins.
Vitamin C’s Relevance to COVID-19
The critical and often fatal phase of COVID-19 occurs with the excessive generation of potent proinflammatory cytokines and chemokines. This results in the development of multi-organ failure. It is associated with neutrophil migration and accumulation within the lung interstitium and bronchioalveolar space - a key determinant of ARDS (Acute respiratory distress syndrome).
Ascorbic acid concentrations are three to ten times higher in the adrenal glands and pituitary than in any other organ. Under conditions of physiological stress (ACTH stimulation), including viral exposure, vitamin C is released from the adrenal cortex resulting in a fivefold increase in plasma levels.
Vitamin C enhances cortisol production and potentiates the anti-inflammatory and endothelial cytoprotective effects of glucocorticoids. Exogenous glucocorticoid steroids are the only proven treatment for COVID-19. Vitamin C, a pleiotropic stress hormone, plays a critical role in mediating the adrenocortical stress response, particularly in sepsis, and protecting the endothelium from oxidant injury.
Colds are caused by over 100 different virus strains, some of which are coronaviruses.
Given the effect of vitamin C on colds - reduced duration, severity, and the number of colds - vitamin C administration may reduce conversion from mild infection to the critical phase of COVID-19.
Vitamin C supplementation is observed to reduce the length of ICU stay, shorten the ventilation time in critical COVID-19 patients, and reduce sepsis patients' mortality requiring vasopressor treatment.
Vitamin C dosage
The authors discuss the safety of oral and intravenous administration of vitamin C, considering the various scenarios of diarrhea, kidney stones, and kidney failure during high dosages. A safe, short-term high dose of 2-8 g/day may be recommended (cautiously avoiding those with a history of kidney stones or kidney disease from high doses). Being water-soluble and thus excreted within hours, dose frequency is important to maintain sufficient blood levels during active infection.
Vitamin C is known to avoid infections and improve immune responses. With specific reference to the critical phase of COVID- 19, vitamin C plays a critical role. It downregulates the cytokine storm, protects the endothelium from oxidant injury, has an essential role in tissue repair, and improves immune responses against infections.
Vitamin C shows promising results when administered to the critically ill.
The authors recommend that people in high-risk groups for COVID-19 mortality and at risk of vitamin C deficiency should be encouraged with vitamin C supplementation daily. They should ensure vitamin C adequacy at all times and increase the dose when virally infected to up to 6-8 g/day. Several dose-dependent vitamin C cohort studies are underway across the world to confirm its role in mitigating COVID-19 and better understand its role as therapeutic potential.
Preprints publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Holford, P.; Carr, A.; Jovic, T.H.; Ali, S.R.; Whitaker, I.S.; Marik, P.; Smith, D. Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19. Preprints 2020, 2020100407 (doi: 10.20944/preprints202010.0407.v1). https://www.preprints.org/manuscript/202010.0407/v1