Vitamin C in COVID-19 (SARS-CoV-2) – Updates
The use of Vitamin C (Ascorbic Acid) in the prevention and treatment of COVID-19 (aka SARS-CoV-2) has received much attention in the popular media and in scientific journals for the past year. This review will look at two critical updates from the science:
1. What do we know and has been published about intravenous Vitamin C (IVC) in patients with COVID-19 (COVID).
2. What about this new study that was just published on oral Vitamin C and Zinc that said it did not help COVID patients?
Vitamin C and COVID, what do we know:
Almost a year ago I was asked by the International Society for Orthomolecular Medicine to create and present a course regarding Vitamin C and viral illness, specifically its potential for use in COVID. This was partly because in cancer research that was partially funded by the US National Institutes of Health, I had headed the IV therapy portion of the trial and had a long background with IVC. In that video / slide presentation (still available online [1]) I describe the pharmacology and use of oral Vitamin C and IVC, its use early in the COVID epidemic in China and its potential uses in COVID going forward. In class I discuss in depth concepts around the use of Vitamin C in humans and our unique requirements for it, especially when ill. It is a good “deep dive” should you wish to have such a resource.
Why would IVC or oral Vitamin C help?
There are many potential immune system dependent processes helped by the Vitamin C in our bodies. In addition to that humans are one of few mammals who do NOT make their own Vitamin C, we must get it from food and drink. Couple that with the fact that when humans are under stress and sick their Vitamin C levels drop (sometimes to undetectable levels) it might seem logical that adding it into a sick human may improve immune response. I’ll reference more later (and I go into this in depth in the class [1]), but that is the basic idea.
Following that class, I was asked by some interested government officials in a few US States to provide a protocol for hospital use which would mirror that used in China with early reports of success. I wrote that protocol [2] and at about the same time a group of authors led by Ba X Hoang began publication of a paper entitled “Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection” which was published in October of 2020 [3]. At that point early in 2020 we were all basing our recommendations on two main factors, one being our own and others use of IVC in infections and sepsis and the other being the early case reports from China using IVC in the hospital with COVID patients.
What was the early Chinese experience with hospitalized COVID patients and IVC?
As mentioned above in March 2020 Cheng [4] and me [1,2] reported individual cases and one unpublished case series from China that showed incredible results. These included ICU patients in respiratory failure recovering with IVC use, and a group of hospitalized COVID patients who received IVC compared to patients who did not, finding shorter hospital stays and lower mortality in the IVC group. Later Cheng updated and added to the case reports and scientific thinking in an excellent July 2020 publication [5].
Regarding the IVC and COVID studies, what have we found out?
As is usual in science it is important to verify observations through controlled trials to find out if the initial observations can be reproduced. Starting early in 2020 many groups began just such controlled trials on IVC (and some using oral Vitamin C). While there are several trials pending (most reported on by Hoang, et.al [3]) there are two IVC trials in human COVID patients which have been published. Both are referenced below (anyone can look them up online if all the detail is required) but in the comments below I will outline the major findings.
In Kumari et. al [6] they enrolled 75 patients in the placebo arm (standard care only) and 75 in the IVC arm (IVC plus standard care), all of whom were hospitalized with COVID. The dose of IVC was modest by many standards (a 70 kilogram / 154-pound person would receive 3.5 grams / 3,500 milligrams IVC per 24 hours). For those in the IVC arm the days to become symptom free were less (average 2.5 less days) and they also had shorter hospital stays (by almost three days). Both outcomes were statistically significant. The study did not reach statistical significance (so no conclusion can be made) in overall mortality or the need for mechanical ventilation.
In Zhang et. al [7] they enrolled 29 patients in the placebo arm and 27 in the IVC arm. (Of note they wanted a larger study population, but they were not having as many new COVID hospitalizations, so they capped the number at 56). All received standard care in the hospital and the placebo group had sterile water in their IV and the IVC group had 24 grams / 24,000 milligrams IVC given every 24 hours. This is obviously a higher dose than used by Kumari et. al [6] but is the dose I published in the hospital use guidelines [2] in early 2020. They measured many biochemical and physical parameters. Many of the data collected did not reach statistical significance (mainly due to the small number of patients) so while they are reported in the paper no conclusions can be drawn from them. There was however statistical significance in the following areas. The need for mechanical ventilation was not different between the two groups. While overall mortality was not different between the groups the probability of death was lower in the IVC group in general and much lower in those with severe COVID who received IVC. Also, a critical lung function measurement “P/F” (PaO2/FiO2) was increased in the IVC (the direction desired for health) by over 1.5 times that of the placebo group. Additionally, statistical significance was found in a critical inflammatory marker “Interleukin-6” (Il-6 one of the causes of the infamous and potentially deadly “cytokine storm”) which was eight times lower in the IVC group. (This is significant as some of the new biological drugs being studied and proposed to improve the course of COVID hospitalization [8] are monoclonal antibodies against Il-6 (they block it / IVC lowers it).
There were no negative interactions between IVC and the standard hospital therapies and no patients had to drop out due to reactions to IVC in either study. These may seem like small findings but are critically important for hospitals not currently using IVC to know.
What about that oral Vitamin C and Zinc study?
The recent publication of “Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial.” in the Journal of the American Medical Association [9] is currently making the rounds in media as a negative study for Vitamin C, Zinc or the combination in COVID patients.
Above I mentioned that I was only going to report on data from studies that reached “statistical significance” which is the idea that the result is not due to pure chance but rather some factor (such as the one being studied). One measurement of statistical significance is the “p” value of the data, and typically the lower the number the better (for example on the IVC studies p values of 0.01 to 0.00001 reached statistical significance and those of 0.04, 0.17, 0.40 and higher did not). Although this study set out originally to use a cut off of a p-value under 0.001 compared with placebo as a “superior therapy” none of its findings reached that level or even 0.01. What does this mean? Based on their criteria their primary and secondary endpoints had p values of 0.28 to 0.97 (none reached significance). In their critique of their data, they did not bring this up but did mention “Furthermore, the doses of zinc and ascorbic acid, while well tolerated, could be lower than amounts needed to shorten the duration of symptoms…” – A good point, but with no data reaching statistical significance that is a guess as well.
So, if we use the rules I started with and only report statistically significant data there is nothing at all to report from this study. The study being published with no significant data may be fine to do but reporting “Vitamin C and Zinc fail with COVID” as is happening now is just dishonest on the part of the media services reporting it.
Many prior publications (including [3,5,10]) referenced below would support the idea that oral Vitamin C (as well as many other nutrients [11]) is not only generally helpful for immune system maintenance and support but also in the setting of viral illness such as COVID. And I would say their concern in the paper that maybe it was “not enough treatment time” is also accurate.
**Short version: That study has no statistical significance and shouldn’t be reported or used to make decisions.
Where do we go from here?
We have an available intervention that certainly can be used in the hospital (IVC) as it is in a few US hospitals and many in other countries that shows exceptional safety as well as benefit to symptoms, length of hospital stay, certain lung functions and potential mortality. It had no negative effect on any other hospital therapies and no study patients dropped out due to IVC adverse events.
Additionally, IVC is known to lower Il-6 which is the target of much more expensive therapies [8] being fast tracked in COVID hospital care.
And not from a formal study but rather my own experience in hospitalized COVID patients those who had hospital staff who implemented IVC were able to be discharged and get off mechanical ventilation and those who did not sadly passed away in the ICU. True this is just my anecdotal experience, but it matches what we are and have been seeing in the peer-reviewed data.
Any hospitals not using IVC should strongly consider it. There are data presented here and a straightforward hospital use guideline [2] is linked below. It is an FDA approved medication for intravenous use sold under the trade name ‘Ascor’ (McGuff Pharmaceuticals Inc.) and is available to any hospital pharmacy.
As for oral supplements while none are proven curative there is a great deal of data around vitamins D and C as well as Zinc and many other nutrients [11] in COVID. There is no reason not to consider these in most people and no reason not to include IVC in hospitalized patients.
References:
1. Anderson PS. Video presentation “Vitamin C and Coronavirus”. https://isom.ca/vitamin-c-coronavirus/
2. Anderson PS. Intravenous Vitamin C for Hospital use in COVID-19. https://isom.ca/article/intravenous-ascorbic-acid-for-supportive-treatment-in-hospitalized-covid-19-patients/
3. Hoang BX, Shaw G, Fang W, Han B. Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection. J Glob Antimicrob Resist. 2020;23:256-262. doi:10.1016/j.jgar.2020.09.025
4. Cheng RZ. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?. Med Drug Discov. 2020;5:100028. doi:10.1016/j.medidd.2020.100028
5. Cheng RZ, Kogan M, Davis D. Ascorbate as Prophylaxis and Therapy for COVID-19-Update From Shanghai and U.S. Medical Institutions. Glob Adv Health Med. 2020;9:2164956120934768. Published 2020 Jul 20. doi:10.1177/2164956120934768
6. Kumari P, Dembra S, Dembra P, Bhawna F, Gul A, Ali B, Sohail H, Kumar B, Memon MK, Rizwan A. The Role of Vitamin C as Adjuvant Therapy in COVID-19. Cureus. 2020 Nov 30;12(11):e11779. doi: 10.7759/cureus.11779. PMID: 33409026; PMCID: PMC7779177.
7. Zhang, J., Rao, X., Li, Y. et al. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann. Intensive Care 11, 5 (2021). https://doi.org/10.1186/s13613-020-00792-3
8. Salama C, Han J, Yau L, et.al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021 Jan 7;384(1):20-30. doi: 10.1056/NEJMoa2030340. Epub 2020 Dec 17. PMID: 33332779; PMCID: PMC7781101.
9. Thomas S, Patel D, Bittel B, Wolski K, Wang Q, Kumar A, Il’Giovine ZJ, Mehra R, McWilliams C, Nissen SE, Desai MY. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2021 Feb 1;4(2):e210369. doi: 10.1001/jamanetworkopen.2021.0369. PMID: 33576820.
10. Feyaerts AF, Luyten W. Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19?. Nutrition. 2020;79-80:110948. doi:10.1016/j.nut.2020.110948
11. Anderson PS COVID and Nutrients – Summary. https://www.consultdranderson.com/nutrients-and-covid-19/
