A brief review of the Safety and Effectiveness of Vitamins C and D in Covid-19 Treatment
This is for information exchange only, not to be used without the supervision of a trained and experienced physician.
Cytokine storm has recently been recognized as the key pathology responsible for the severe symptoms of Covid-19 and other viruses and non-viral agents. The underlying biochemical cause of cytokine storm is excessive oxidative stress. Cytokine storm and its associated oxidative stress appears to be a universal non-specific mechanistic pathway common among many causative agents, for example viruses, that leads to severe clinical disease.
A biochemical sequence known as “lipid peroxidase chain reaction” (LPCR) plays a critical role in oxidative stress and cytokine storm. Prevention and blocking the occurrence of cytokine storm/oxidative stress appears to be a logically sound and effective strategy to prevent the severe symptoms of Covid-19. If this could be performed world-wide, it could reduce the devastating medical, economic and societal impact of the Covid-19 pandemic. Preventing or blocking LPCR and the excessive oxidative stress requires intact antioxidant systems, especially the antioxidant vitamins and nutrients, including vitamins C, E, CoQ10, alpha lipoic acid, glutathione and niacin (to promote NADP+/NADP), selenium and others. Insufficiency or absence of any of these antioxidant agents may render these antioxidant systems ineffective, which may be responsible for the inconsistent results of antioxidant therapies in the literature. Here we propose an integrative and systematic therapy that includes these antioxidant vitamins, minerals, and nutrients. The “universal and non-specific nature” of cytokine storm/oxidative stress makes possible a pre-emptive treatment to prevent or block cytokine storm/oxidative stress induced by severe diseases, even before full recognition of the underlying causative agent. This is very significant because it allows us to potentially prevent and block a pandemic of a new virus or a new viral mutant when it happens without requiring the extended time needed to develop a specific drug or vaccine treatment. With the seemingly endless mutations of SARS-Cov-2, we may still have time to apply this strategy to break the Covid-19 pandemic1.
- Safety of high dose vitamin C.
Vitamin C, when taken by mouth or intravenously, is very safe, even at high doses. “Vitamin C has low toxicity and is not believed to cause serious adverse effects at high intakes. The most common complaints are diarrhea, nausea, abdominal cramps, and other gastrointestinal disturbances due to the osmotic effect of unabsorbed vitamin C in the gastrointestinal tract” , according to the NIH Office of Dietary Supplements2.
Vitamin C can also be safely administered at high doses of up to 1.5 g/kg body weight, when properly used under an experienced physician. “Studies have shown that vitamin C can be safely administered to healthy volunteers or cancer patients at doses up to 1.5 g/kg…” according to the National Cancer Institute, NIH3. For a 170-pound person, up to 115 grams of vitamin C can be safely given intravenously.
- Vitamin C has immune-enhancement properties.
- Reduces oxidative stress, as an antioxidant4 5 6
- Reduces inflammation6
- Supports epithelial barrier function (e.g., alveolar membranes) and endothelial barrier protection7
- Supports differentiation and maturation of T cells and NK cells8
- Enhances microbial killing and antibody production8 9
- Enhances migration of immune cells to sites of infection8 9
- Impaired chemotaxis observed in severely infected patients6
- Protects immune cells from oxidative burst (rapid release of ROS)6
- Promotes programmed cell death (cell death)6
- Vitamin C deficiency is common, especially in Covid-19 patients
- “The available evidence indicates that vitamin C hypovitaminosis and deficiency is common in low- and middle-income countries and not uncommon in high income settings.”10 Vitamin C deficiency is also common in the Western countries11 12. Insufficiency and deficiency of micronutrients including vitamin C and D are also rampant in the US. A recent US national nutrition survey found “Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc.”13
- Lower plasma vitamin levels are associated with greater risk of organ failure and death in patients with septic shock14
- The average plasma vitamin C concentrations in COVID-19 patients were five times lower than in healthy volunteers15
- Vitamin C levels are undetectable in more than 90% of COVID-19-associated ARDS patients16
- Vitamin C intake of at least 2-3 g/day may be required to maintain normal plasma vitamin C levels during viral infection12
- Covid-19 patients had significantly lower plasma vitamin C levels than controls, longer hospital stays, and higher mortality17
- Clinical studies show effectiveness of Vitamin C in Covid-19 treatment.
- A review of twelve studies, including five “gold standard” randomized controlled trials, shows that this simple vitamin saves lives when given in the right dose18. Vitamin C can prevent a serious Covid infection. The current level of evidence from the RCTs suggests that intravenous vitamin C intervention may improve oxygenation parameters, reduce inflammatory markers, decrease days in hospital and reduce mortality, particularly in the more severely ill patients. High doses of oral vitamin C supplementation may also improve the rate of recovery in less severe cases. No adverse events have been reported in published vitamin C clinical trials in COVID-19 patients19. Vitamin C has been shown to be effective in the prevention and treatment of various other viral infections12. Despite the fact that vitamin C is safe, now proven effective, inexpensive and widely available, it is not widely accepted nor promoted by medical authorities or hospitals. In some instances, high dose vitamin C usage is even prohibited, allegedly due to medical reasons.
- Beneficial aspects of high-dose intravenous vitamin C in patients with severe COVID-19 pneumonia: a retrospective case series20.
- High-dose intravenous vitamin C for the treatment of patients with moderate to severe COVID-19.
- Improvements in inflammatory response and immune and organ function are beneficial.
- Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis21.
- Daily IV infusions of 3.5 and 14 g of vitamin C for four days significantly reduced multiorgan failure scores, with the higher dose showing twice as much reduction in failure scores as the lower dose.
- Vitamin C improves the disease and shortens ICU stay22.
- Vitamin C may shorten duration of mechanical ventilation in critically ill patients23
- In this RCT, hospitalized elderly patients with acute respiratory infection received 200 mg of vitamin C orally per day for 4 weeks. Taking vitamin C can reduce the severity of disease and reduce mortality24.
- Supports transcription of antimicrobial peptides that have activities against various bacteria, viruses, and fungi 25 26 27.
- Induces autophagy (cleaning out of damaged or unnecessary cellular components) thereby enhancing clearance of viruses and viral constituents28.
- Modulates innate and adaptive immune activity29.
- Regulates growth and differentiation of several types of immune cells30.
- Suppresses over-expression of pro-inflammatory cytokines30.
- Supports gut integrity and gut microbial balance31.
- Helps maintain the integrity of epithelial tight junctions which decreases risk of infection and pulmonary edema32.
- Helps maintain TH1:TH2 immune balance28 by reducing TH1 and inducing TH2 immune responses26 (Bae & Kim, 2020).
Vit D in Covid-19
- Serum vitamin D3 levels < 27 ng/ml: significant increase in Covid-19 mortality. Vit D3 > 30 ng/ml. the mortality rate is close to zero.
- Large study of >1.4 million people (54 studies) again shows: low blood vitamin D levels associated with higher risk of Covid-19 infection, ICU admission and mortality33
- The 2-year survey of 662,835 U.S. military veterans concluded that vitamin D3 and vitamin D2 supplementation reduced the risk associated with COVID-19 infection by 20% and 28%, and reduced the risk of death from COVID-19 infection within 30 days. The associated risk reductions were 33% and 25%.34
- 50,000 IU per day x 5 days in COVID-19 patients resulted in less inflammation and shorter recovery times compared to patients receiving 1000 IU/day35.
- Combined with standard care, early high-dose vitamin D therapy avoids ICU admission in COVID-19 patients36.
- “The mean vitamin D3 dose was 35,291 ± 21,791 IU per day…We found a very weak relationship between oral doses of vitamin D3 and subsequent calcium levels, both in serum and 24-hour urine.”37
Intervention of Covid-19:
Case 1. Mr. W, an 80-year-old man in China with history of type 2 diabetes, hypertension, brain infarction and Alzheimer’s disease, has been in ICU for Covid-19 pneumonia, high fever (~39.5 C) for 20 days, with standard hospital care including auxiliary oxygenation, without much improvement. The family sought our consultation. We recommended our Integrative Orthomolecular Covid-19 Treatment Protocol. He improved quick with the high fever gone the same night and never came back. His inflammatory markers and other lab parameters improved. He was off auxiliary oxygenation and moved from ICU to a regular ward on day 3. The family was pleasantly surprised.
Case 2. A 4-year-old boy was diagnosed of Covid-19 pneumonia with high fever of 39 C. There was no bed available at the hospital. The mother sought our consultation and we recommended our Integrative Orthomolecular Covid-19 Treatment Protocol. The boy improved significantly the next morning with fever gone, with some residual respiratory symptoms. By the 2nd day, the boy was happy and playful. The mother thanked us profusely and called the Protocol “miraculous”.
Case 3. We previously reported a case of rapid recover from severe Covid-19 (1). Briefly, Robert, a 60-year-old man with diabetes, was admitted into an ICU at a local hospital with severe Covid-19 pneumonia. His lab showed very high inflammatory markers (ferritin, D dimer, CRP) as well as reduction of oxygen saturation. We offered the same protocol (adjusted to the hospital requirement). The patient recovered quickly.
Case 4. A diabetic whose blood sugar has been stable on a low-carb diet, suffered a stroke and was intubated 2 weeks after receiving 2 doses of the Covid-19 vaccine. He later developed pneumonia with a fever. The family consulted me and I recommended similar antiviral and antioxidant therapies with detailed guidance and follow-up. Within 3-4 days, his fever subsided.
Intervention of Non-Covid cases:
Case 5. Acute liver failure. Dr. F is a professor of music and an old friend of mine in the United States. About a year ago, her 80-year-old mother was admitted to the ICU with acute liver failure. Dr. F received a notice that his mother was critically ill. Her journey back to China to visit her mother was extremely difficult due to Covid travel restrictions. She consulted with me and I recommended a comprehensive antioxidant regimen (similar to the one described above). I also discussed options with her mother’s attending physician. In just 2-3 days, her mother has improved and was transferred from the ICU to the general ward, and later discharged to home care. Her mother is in good health and continues to receive antioxidant therapy including vitamin C.
The following is what we have been using for our clients (primarily in China. For information exchange only. The information here should not be used without a qualified physician’s supervision).
Integrative Orthomolecular Covid-19 Prevention Protocol.
- Vitamin C, 3,000mg – 10,000mg/day, divided into 2-3 times.
- Or liposomal vitamin C (Liposomal-Vit C), 1-2 grams / day.
- Vitamin D3, 5,000 IU/day; blood vitamin D3 levels of 50 – 100 ng/ml are recommended.
- Zinc, 30 mg/day.
- Magnesium ions, 500-1000 mg/day.
- 1-3% hydrogen peroxide atomized inhalation, 5-15 minutes, return from going out or have suspicious contact.
- Cheng TotoCell Nutrition (with high levels of all vitamins plus mitochondrial and micronutrients)
- Vitamin E, 400 – 2000 IU/day.
- Quercetin (promoting the virus-killing effect of zinc) 500 mg, 3-4 times/day.
- Melatonin (melatonin 5 – 20mg/night), a powerful immune booster
Integrative Orthomolecular Covid-19 Treatment Protocol.
- Vitamin C, 1,000 – 3,000 mg/hour (first to diarrheal dose).
- Or liposomal vitamin C (Liposomal-Vit C), 1-2 grams/time, 1-4 times a day. Or IV: 30-60 g/day.
- Vitamin D3, 50,000IU/day x 5-7 days; then, 5,000 IU/day; after 1-2 months, blood vitamin D3 (50-100 ng/ml).
- Liposomal Glutathione (Liposomal-GSH), 1-2 g/day
- Zinc, 50-100 mg/day x 7-10 days.
- Magnesium, 500-1000 mg/day.
- 1-3% hydrogen peroxide atomized inhalation, 5-15 minutes, 3-4 times/day.
- Melatonin (melatonin 5 – 20mg/night), a powerful immune booster.
- Cheng TotoCell Nutrition (with high amounts of all vitamins plus mitochondrial and micronutrients)
- Vitamin E, 400 – 2000 IU/day.
- Quercetin (promoting the virus-killing effect of zinc) 500mg, 3-4 times/day.
- Other: healthy lifestyle habits, sun exposure, exercise, other antioxidants.
- Cheng, R. A Hallmark of Covid-19: Cytokine Storm/Oxidative Stress and its Integrative Mechanism. http://orthomolecular.org/resources/omns/v18n03.shtml (2022).
- Office of Dietary Supplements – Vitamin C. https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/.
- Intravenous Vitamin C (PDQ®)–Health Professional Version – NCI. https://www.cancer.gov/about-cancer/treatment/cam/hp/vitamin-c-pdq (2013).
- Richard Cheng MD PhD. Oxidative Stress, Ignored Key Pathology of Covid-19. (2021).
- Cheng, Richard Z. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)? Medicine in Drug Discovery 5, 100028 (2020).
- Milani, G. P., Macchi, M. & Guz-Mark, A. Vitamin C in the Treatment of COVID-19. Nutrients 13, 1172 (2021).
- Gröber, U. & Holick, M. F. The coronavirus disease (COVID-19) – A supportive approach with selected micronutrients. Int J Vitam Nutr Res 92, 13–34 (2022).
- Iddir, M. et al. Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis. Nutrients 12, 1562 (2020).
- Cerullo, G. et al. The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19. Front Immunol 11, 574029 (2020).
- Rowe, S. & Carr, A. C. Global Vitamin C Status and Prevalence of Deficiency: A Cause for Concern? Nutrients 12, 2008 (2020).
- Gröber, U. & Holick, M. F. The coronavirus disease (COVID-19) – A supportive approach with selected micronutrients. Int J Vitam Nutr Res 92, 13–34 (2022).
- Holford, P. et al. Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19. Nutrients 12, E3760 (2020).
- Reider, C. A., Chung, R.-Y., Devarshi, P. P., Grant, R. W. & Hazels Mitmesser, S. Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES. Nutrients 12, E1735 (2020).
- Borrelli, E. et al. Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk. Crit Care Med 24, 392–397 (1996).
- Xing, Y. et al. Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding. J Pharm Biomed Anal 196, 113927 (2021).
- Chiscano-Camón, L., Ruiz-Rodriguez, J. C., Ruiz-Sanmartin, A., Roca, O. & Ferrer, R. Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome. Crit Care 24, 522 (2020).
- Sinnberg, T. et al. Vitamin C Deficiency in Blood Samples of COVID-19 Patients. Antioxidants (Basel) 11, 1580 (2022).
- Holford, P., Carr, A. C., Zawari, M. & Vizcaychipi, M. P. Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence. Life (Basel) 11, 1166 (2021).
- Carr, A. C. Vitamin C in Pneumonia and Sepsis. in Vitamin C: New Biochemical and Functional Insights (eds. Chen, Q. & Vissers, M. C. M.) (CRC Press, 2020).
- Zhao, B. et al. Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study. Ann Palliat Med 10, 1599–1609 (2021).
- Fowler, A. A. et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med 12, 32 (2014).
- Hemilä, H. & Chalker, E. Vitamin C Can Shorten the Length of Stay in the ICU: A Meta-Analysis. Nutrients 11, (2019).
- Hemilä, H. & Chalker, E. Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis. J Intensive Care 8, 15 (2020).
- Hunt, C., Chakravorty, N. K., Annan, G., Habibzadeh, N. & Schorah, C. J. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res 64, 212–219 (1994).
- Vyas, N. et al. Vitamin D in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects. J Am Coll Nutr 40, 632–645 (2021).
- Bae, M. & Kim, H. The Role of Vitamin C, Vitamin D, and Selenium in Immune System against COVID-19. Molecules 25, 5346 (2020).
- Mitchell, F. Vitamin-D and COVID-19: do deficient risk a poorer outcome? Lancet Diabetes Endocrinol 8, 570 (2020).
- Malaguarnera, L. Vitamin D3 as Potential Treatment Adjuncts for COVID-19. Nutrients 12, 3512 (2020).
- Radujkovic, A. et al. Vitamin D Deficiency and Outcome of COVID-19 Patients. Nutrients 12, 2757 (2020).
- Sulli, A. et al. Vitamin D and Lung Outcomes in Elderly COVID-19 Patients. Nutrients 13, 717 (2021).
- Charoenngam, N. & Holick, M. F. Immunologic Effects of Vitamin D on Human Health and Disease. Nutrients 12, 2097 (2020).
- Shakoor, H. et al. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19? Maturitas 143, 1–9 (2021).
- Chiodini, I. et al. Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes. Front Public Health 9, 736665 (2021).
- Gibbons, J. B. et al. Association between vitamin D supplementation and COVID-19 infection and mortality. Sci Rep 12, 19397 (2022).
- Ohaegbulam, K. C., Swalih, M., Patel, P., Smith, M. A. & Perrin, R. Vitamin D Supplementation in COVID-19 Patients: A Clinical Case Series. Am J Ther 27, e485–e490 (2020).
- Entrenas Castillo, M. et al. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. J Steroid Biochem Mol Biol 203, 105751 (2020).
- Amon, U., Yaguboglu, R., Ennis, M., Holick, M. F. & Amon, J. Safety Data in Patients with Autoimmune Diseases during Treatment with High Doses of Vitamin D3 According to the ‘Coimbra Protocol’. Nutrients 14, 1575 (2022).