In the final part of this 3-part blog series on important nutrients in the fight against viral illness following on from part 1 discussing quercetin and part 2 discussing zinc, we will look at the role of vitamin C, which has been used to prevent and treat viral infections since Linus Pauling, PhD endorsed its benefits decades ago.

Vitamin C – a brief history

Vitamin C (also called ascorbate, or ascorbic acid) was one of the first nutrients to be intensely studied for its role in overall health and immune support. It is an essential water-soluble nutrient that functions as a potent antioxidant due to its ability to readily donate electrons and reduce oxidative stress. Vitamin C also contributes to the production of collagen (skin, tendons, ligaments, bone), carnitine (cardiovascular function, energy production), and neurotransmitters (catecholamines) via support of various enzymes involved in their production. Vitamin C has potent anti-inflammatory properties and influences cellular immunity and vascular integrity. Linus Pauling, PhD proposed that high dose vitamin C could reduce the duration and severity of the common cold and recommended a 2000 mg daily dose for prophylaxis. He was both ridiculed and revered in his day for his views on vitamin C, and controversy still exists around whether high-dose vitamin C plays a role in the prevention and treatment of illness.

The Linus Pauling Institute at Oregon State University, where Dr. Pauling attended as an undergraduate, confirms the research that vitamin C is supportive of the immune system and is a potent antioxidant [1]. The institute does state, however, that dosages of only 400 mg per day are needed to maintain plasma and cell saturation in healthy non-smokers. This recommendation is based on current scientific evidence, which the Institute notes is incomplete because of ongoing research into the many roles of vitamin C in the human body [1] and the pharmacokinetics in differing populations based on age, lifestyle and health status.

Beyond staving off deficiency, Dr. Pauling was most interested in the therapeutic benefits of vitamin C to both prevent and treat disease. The Linus Pauling Institute acknowledges that people suffering from certain diseases, whether acute or chronic, may require substantially larger dosages to achieve optimum levels and derive therapeutic benefit. Interestingly, relying on white blood cell levels of vitamin C, as opposed to serum or plasma, may give us a better idea of tissue distribution, as vitamin C is concentrated in the leukocytes, the eyes, the adrenals, the pituitary and the brain[1].

Vitamin C in immune support

The use of Vitamin C to support immune system function has become a mainstay in the prevention and treatment of viral illness and has shown benefit in many chronic health conditions such as cardiovascular disease, diabetes and cancer. Even in small amounts, vitamin C can protect proteins, fats, carbohydrates, DNA and RNA from damage by free radicals and reactive oxygen species (ROS) that are generated during normal metabolism, immune system response and from exposure to toxins and pollutants. Vitamin C also participates in redox recycling of other important antioxidants including quercetin, which keeps their antioxidant capacity intact and supports overall function.

Vitamin C has been shown to stimulate both the production and function of white blood cells (leukocytes), especially neutrophils, lymphocytes and phagocytes. These immune cells accumulate vitamin C in high concentrations which protects them from oxidative damage as they respond to infections. In response to invading microorganisms, leukocytes produce superoxide radicals, hypochlorous acid, and peroxynitrite. These reactive oxygen species kill pathogens but can also damage the leukocytes themselves and contribute to an enhanced inflammatory reaction. As an antioxidant, vitamin C protects leukocytes from self-inflicted oxidative damage thereby keeping inflammation under control.

Vitamin C has also been shown to increase interferon production in vitro and can enhance the chemotactic and microbial killing capacities of neutrophils making them more effective overall. In support of adaptive immunity, the role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B and T cells [2]. Vitamin C is also needed for apoptosis and clearance of neutrophils from sites of infection by macrophages thereby reducing potential tissue damage. Vitamin C also supports epithelial barrier function, externally through the skin and internally through the mucosal barrier, against pathogen penetration reducing the chance of infection.

Vitamin C and COVID’s cytokine storm

Those who are severely ill with COVID-19 are likely to have elevated inflammatory markers indicative of a cytokine storm. Interleukin-6 (IL-6) is a cytokine and a key inflammatory mediator in the progression of COVID-19. High levels of IL-6 can be predicative of respiratory failure and are associated with an increased risk of mortality. It has been noted that as people age, there is an overexpression of IL-6 during an inflammatory episode and this condition tends to be associated with a higher frequency of organ failure [3]. Another inflammatory mediator in the progression of COVID-19 is endothelin-1 (ET-1) which is a potent vasoconstrictor and proinflammatory cytokine. The increased expression of ET-1 has been associated with pneumonia, pulmonary hypertension, interstitial lung fibrosis and acute respiratory distress syndrome (ARDS).

Vitamin C can reduce the hypersecretion of IL-6, ET-1 and C-reactive protein as well as other inflammatory cytokines, thereby reducing the chance of developing an extreme inflammatory reaction when the immune system is activated against a viral pathogen. Vitamin C reduces oxidative stress associated with immune stimulation and aids in the healing process of tissues damaged through the inflammatory process. Vitamin C may also inhibit the formation of neutrophil extracellular traps (NETs) which have been associated with organ damage [3]. NETs are webs formed from chromatin, microbicidal proteins, and oxidant enzymes, which are produced by neutrophils to contain infections [4]. However, if they are not kept under control, NETs can potentiate inflammation and microvascular thrombosis. With COVID-19, this process occurs in the lungs and contributes to acute respiratory distress syndrome (ARDS).

Dietary sources and supplemental vitamin C

The good news is that vitamin C is very abundant in food - it is found in most plant-based foods and accompanies the many phytonutrients that benefit from its antioxidant capacity. Foods rich in vitamin C include bell peppers, strawberries, guavas, oranges, tomatoes, broccoli, kale, and brussels sprouts. Most fruits and vegetables are likely to have some vitamin C, so eating a broad variety should provide a decent amount. In foods, vitamin C exists as a complex with bioflavonoids, minerals and other nutrients where they exist in mutual support of absorption and utilization. The uptake of vitamin C by immune cells increases during an infection to support antioxidant needs and key aspects of immune function. Oral tolerance of vitamin C can limit how much we can take in a 24-hour period; however, during acute illness, oral tolerance to vitamin C can increase greatly as the body effectively utilizes this nutrient to support immune function, increase antioxidant capacity and reduce inflammation. Oral supplementation and IV administration have the ability to increase tissue levels to exert a desired therapeutic effect that cannot be attained from food alone. 

According to the NIH, the Recommended Daily Allowance (RDA) of vitamin C, set at 90 mg per day for adult men and 75 mg per day for adult women, is based on the vitamin C needed to maintain near-maximal neutrophil concentration with minimal urinary excretion of ascorbate [5]. The current RDA is generally directed toward preventing deficiency rather than supporting health or treating disease. The Tolerable Upper Intake Level (UL) for adults is set at 2000 mg per day, beyond which the adverse effects are osmotic diarrhea and gastrointestinal disturbances.

Use of high dosages of vitamin C

Higher dosages of vitamin C, beyond that which prevents deficiency, may be a necessity for good health due to the ever-increasing exposure to environmental toxins and the existence of inflammation which adds to the burden of oxidative stress. The dosage that is considered reasonable for prophylaxis is 2000 mg per day – just what Dr. Pauling recommended. For those who are acutely ill, higher oral dosages up to 10 grams per day may be tolerated. Like quercetin, the limits of intestinal absorption can reduce that amount of vitamin C that can be taken as a single dose; however, the use of liposomal vitamin C can increase intestinal absorption and enhance cellular permeability allowing for higher oral dosing without intestinal upset.

The use of intravenous vitamin C (IV Vit-C) has allowed for administration of much higher dosages which greatly increases cellular concentration and utilization of vitamin C by immune cells. In vitro studies show that high dose vitamin C induces virucidal activity [6]. Reports out of Shanghai show promising results not only during infection, but also as a preventive and post-infection therapy [7]. IV Vit-C improves outcomes with COVID-19 by reducing the chance of a cytokine storm that injures endothelial cells in the lungs, increases neutrophil infiltration, damages the alveolar-capillary barrier and results in uncontrolled inflammation and oxidative stress [6]. The anti-inflammatory and antioxidant effects of vitamin C are potentized through high dose IV administration and has proven to be safe, cost-effective and well-tolerated. The Shanghai Expert Panel noted that those who received IV Vit-C decreased their hospital stay by 3-5 days. Dosages used in the Shanghai study were 100 mg/kg/day for hospitalized patients and 200 mg/kg/day to control a cytokine storm [8]. There are currently clinical trials occurring on the use of IV Vit-C for COVID-19 in the United States and Canada.

This 3-part blog series introduced 3 important nutrients: quercetin, zinc, and vitamin C, which can be considered as nutritional support for viral illness. Limiting viral replication early in the disease process may reduce the severity of its inflammatory phase, especially in those with comorbid conditions and nutrient deficiencies. Use of quercetin, zinc, and vitamin C together potentiates their individual effects and they are often combined in single product formulations.

Related Resources

• Naturopathic Therapy for Prevention and Support of Viral Illness: Part 1 – Quercetin
• Naturopathic Therapy for Prevention and Support of Viral Illness: Part 2 - Zinc

References

1. Linus Pauling Institute. Vitamin C. Available at: https://lpi.oregonstate.edu/mic/vitamins/vitamin-C.
2. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9:1211.
3. Feyaerts AF, Luyten W. Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19? Nutrition. 2020;79-80:110948.
4. Zuo Y, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11):e138999.
5. National Institutes of Health Office of Dietary Supplements - Vitamin C Fact Sheet for Health Professionals. Available at: https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/ .
6. Boretti A, Banik BK. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition. 2020;12:100190.
7. Cheng RZ, et al. Ascorbate as Prophylaxis and Therapy for COVID-19-Update from Shanghai and U.S. Medical Institutions. Glob Adv Health Med. 2020;9:2164956120934768.
8. Anderson PS. Intravenous ascorbic acid for supportive treatment in hospitalized COVID-19 patients. J Orthomolecular Med 2020;35(1).