COVID-19: Blood Biomarkers - Vitamin C

Vitamin C is more than just a vital amine in the COVID-19 fight

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

Vitamin C possesses antiviral, anti-inflammatory, antioxidant, and immunomodulating effects, making it a focus of research in COVID-19.

The ODX COVID-19 Series

1. COVID-19: The pandemic that has become endemic
2. COVID-19: Overlapping risk factors and chronic disease
3. Nutritional status COVID-19: A covert factor in disease susceptibility
4. COVID-19: Blood chemistry biomarker patterns - Clues and patterns lurking just under the surface
5. COVID-19: Blood chemistry biomarker patterns - Down the research rabbit hole
6. COVID-19: Blood Biomarkers - Neutrophils
7. COVID-19: Blood Biomarkers - Albumin
8. COVID-19: BloodBiomarkers - Cytokines
9. COVID-19: Blood Biomarkers - Interleukin-6
10. COVID-19: Blood Biomarkers - Interleukin-10
11. COVID-19: Blood Biomarkers - Vitamin C
12. COVID-19: Blood Biomarkers - Vitamin D
13. COVID-19: Blood Biomarkers - Zinc
14. Biomarker characteristics and blood type - help sharpen the COVID-19 clinical picture
15. COVID-19: Initial indications and conventional interventions
16. COVID-19: Long-term risk reduction - Naturopathic, functional medicine, and nutrition-based approaches to prevention
17. A healthy diet is primary prevention for COVID-19
18. You should have a gut feeling about COVID-19
19. Beyond dietary food patterns…plant-based compounds may mitigate COVID-19 risk
20. Targeted nutrition support in the battle against COVID-19
21. Targeted nutrition support in COVID-19: Armed with vitamin C
22. Targeted nutrition support in COVID-19: In sync with zinc
23. Targeted nutrition support in COVID-19: Micronutrients and phytonutrients are important players
24. Optimal Takeaways for improving immunity and reducing susceptibility to COVID-19
25. Optimal - The Podcast: Episode 8 -Blood Biomarkers and Risk Factors for COVID-19 and its Comorbidities

Unlike most mammals, humans cannot produce vitamin C (ascorbic acid), making it an essential nutrient that must be obtained exogenously.[i] Hepatic production of vitamin C increases under stress (except for humans, primates, and guinea pigs).[ii]

An insufficiency of vitamin C contributes to increased susceptibility to viral infection and the adverse effects of prolonged inflammation.[iii]

A cross-sectional study of 14,519 adults participating in the NHANES III revealed that blood concentrations of vitamin C (and other antioxidants) were inversely correlated with CRP, likely a reflection of antioxidant depletion due to oxidative stress and inflammatory processes.[iv]

Vitamin C: [v]

• Improves epithelial barrier integrity, natural killer cell activity, and neutrophil chemotaxis and phagocytosis
• Stimulates proliferation of lymphocytes and production of interferon
• Reduces release of proinflammatory cytokines
• Scavenges oxygen-free radicals and counteracts oxidative stress from the cytokine storm
• May help prevent ARDS which is characterized by oxidative damage to the lungs
• Deficiency is common in septic patients, with an inverse correlation between serum vitamin C and multi-organ dysfunction in sepsis
• Vitamin C levels in serum and in leukocytes decrease during the increased metabolic demands of infection.
• Supplementation can help replete serum and leukocyte vitamin C if provided in high enough doses.
• Meta-analysis of 1210 critically ill patients showed that providing 3-10 grams of IV vitamin C per day reduced mortality rate.
• Supplementation should be adjusted as needed as high concentrations may be pro-oxidative.
• Vitamin C may interfere with accuracy of glucometer readings due to it having a molecular structure similar to glucose.
• Note that differences in the vitamin C transporter system within the body may influence the efficacy of vitamin C supplementation in certain individuals.[vi]
• High dose supplementation may be contraindicated in those with G6PD dehydrogenase deficiency, renal failure, or those prone to oxalate kidney stones.
• However, therapeutic doses of vitamin C below 16 gram/day may be tolerated in those with G6PD deficiency.[vii]

Low serum vitamin C has been recognized as a factor in pneumonia and sepsis for decades and supplementation has been shown to be therapeutic. These benefits appear to translate into benefits for COVID-19 patients as well. [viii]

• Critically ill patients may need 20-30 times more vitamin C than the general population and several gram doses to normalize serum levels.
• A randomized study of septic ARDS patients demonstrated that 200 mg/kg/day of vitamin C for four days was associated with a lower mortality rate of 30% versus 46% in the placebo group.
• Meta-analysis revealed that vitamin C supplementation resulted in reduced mechanical ventilation and length of ICU stay
• Serum vitamin C levels of 0.41 mg/dL (23 umol/L) are considered hypovitaminosis C and levels below 0.19 mg/dL (11 umol/L) were considered vitamin C deficient
• The World Health Organization recognized adjunctive vitamin C as an intervention with biologic plausibility.
• Several clinical trials are currently investigating the efficacy of vitamin C in the treatment of COVID-19

A small study of critically ill COVID-19 adults with ARDS revealed underlying vitamin C deficiency. The study found that 17 of 18 patients had undetectable serum vitamin C using a detection limit of 0.15 mg/dL (8.5 umol/L), while one patient had a deficient level of 0.24 mg/dL (13.5 umol/L).[ix]

Vitamin C insufficiency was detected in 21 critically ill COVID-19 ICU patients with a mean serum level of 0.39 mg/dL (22.2 umol/L), well below the standard hospital reference value of 0.51 mg/dL (29.1 umol/L). Mean vitamin D levels of 22 ng/mL (55 nmol/L) were also below normal hospital values of 30–100 ng/mL (75-250 nmol/L). Researchers strongly recommend assessing for and correcting insufficiencies of vitamins C and D.[x]

Standard reference range vitamin C

            Quest Diagnostics[xi] Males 0.2-2.1                       Females 0.3-2.7 mg/dL

            Labcorp[xii]                   0.4-2 mg/dL

Optimal ranges of vitamin C are higher than standard lab ranges. [xiii]

Next Up - COVID-19: Blood Biomarkers - Vitamin D

Research

[i] Drouin, Guy et al. “The genetics of vitamin C loss in vertebrates.” Current genomics vol. 12,5 (2011): 371-8. doi:10.2174/138920211796429736

[ii] Hoang, Ba X et al. “Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection.” Journal of global antimicrobial resistance vol. 23 (2020): 256-262. doi:10.1016/j.jgar.2020.09.025 

[iii] Richardson, David P, and Julie A Lovegrove. “Nutritional status of micronutrients as a possible and modifiable risk factor for COVID-19: a UK perspective.” The British journal of nutrition, 1-7. 20 Aug. 2020, doi:10.1017/S000711452000330X 

[iv] Ford, E S et al. “C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults.” European journal of clinical nutrition vol. 57,9 (2003): 1157-63. doi:10.1038/sj.ejcn.1601667

[v] Abobaker, Anis et al. “Overview of the possible role of vitamin C in management of COVID-19.” Pharmacological reports : PR vol. 72,6 (2020): 1517-1528. doi:10.1007/s43440-020-00176-1 

[vi] Patterson, Gregory, Carlos M. Isales, and Sadanand Fulzele. "Low level of Vitamin C and dysregulation of Vitamin C transporter might be involved in the severity of COVID-19 Infection." Aging and disease (2020): 0.

[vii] Hoang, Ba X et al. “Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection.” Journal of global antimicrobial resistance vol. 23 (2020): 256-262. doi:10.1016/j.jgar.2020.09.025

[viii] Carr, Anitra C, and Sam Rowe. “The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19.” Nutrients vol. 12,11 3286. 27 Oct. 2020, doi:10.3390/nu12113286 

[ix] Chiscano-Camón, Luis et al. “Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome.” Critical care (London, England) vol. 24,1 522. 26 Aug. 2020, doi:10.1186/s13054-020-03249-y 

[x] Arvinte, Cristian et al. “Serum Levels of Vitamin C and Vitamin D in a Cohort of Critically Ill COVID-19 Patients of a North American Community Hospital Intensive Care Unit in May 2020: A Pilot Study.” Medicine in drug discovery vol. 8 (2020): 100064. doi:10.1016/j.medidd.2020.100064 

[xi] Quest Diagnostics Vitamin C. 

[xii] Labcorp Vitamin C. 

[xiii] Klimant, E et al. “Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach.” Current oncology (Toronto, Ont.) vol. 25,2 (2018): 139-148. doi:10.3747/co.25.3790