30 October 2020

Vitamin C and COVID-19

Vitamin C, also known as Ascorbic Acid, is an essential water-soluble vitamin that is thought to have beneficial effects in patients with severe and critical illnesses. It is an antioxidant and free radical scavenger that has anti-inflammatory properties, influences cellular immunity and vascular integrity, and serves as a cofactor in the generation of endogenous catecholamines.Because humans may require more Vitamin C in states of oxidative stress, Vitamin C supplementation has been evaluated in numerous disease states, including serious infections and sepsis. Because serious COVID-19 may cause sepsis and acute respiratory distress syndrome (ARDS), the potential role of high doses of Vitamin C in ameliorating inflammation and vascular injury in patients with COVID-19 is being studied.

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.

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.

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-?B 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).

Vitamin C 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 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.

Reference :
1. Wei XB, Wang ZH, Liao XL, et al. Efficacy of vitamin C in patients with sepsis: an updated meta-analysis. Eur J Pharmacol. 2020;868:172889.
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2. Fisher BJ, Seropian IM, Kraskauskas D, et al. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med. 2011;39(6):1454-1460.
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3. Dwivedi, Ramnya: Vitamin C and COVID-19: A Review, News Medical Life Sciences, October 2020.
Avaiable at:
4. 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).