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The study of JAMA on the ineffectiveness of vitamin C and zinc in Covid-19 is incorrect

A study published in JAMA on February 12, 2021 showed that ORAL intake of 8000 mg of vitamin C and/or intake of 50 mg of zinc did not help patients with mild Covid-19 symptoms (1). This study was NOT a double-blind compared to a placebo study (ie the patient knew what he was taking) and did NOT administer INTRAVENOUS vitamin C, but orally vitamin C. In an earlier article (2) I presented a randomized placebo-controlled study that was designed to test high-dose intravenous vitamin C for the treatment of COVID-19 and reduced mortality in critically ill patients by two-thirds (3). The study, led by Professor Zhiyong Peng at Wuhan University Zhongnan University Hospital, began in February 2020 and gave every other critically ill patient inhaled with COVID-19 either 12,000 mg of vitamin C twice daily or sterile water. Neither the patient nor the doctors knew who was taking vitamin C or placebo, so the test was “double blind.”

A recent study looked at giving vitamin C and zinc for mild COVID19 illness. Zinc gluconate and vitamin C, aka ascorbic acid, are commonly available over-the-counter supplements that people often take to treat viral illnesses. Zinc is known to play a role in our immune function by helping to produce antibodies, in addition to enhancing our white blood cell’s ability to fight infection, especially when it comes to neutrophils, a type of white blood cell. There is also some evidence that zinc deficiency increases pro-inflammatory cytokines. Also, studies done on the first SARS virus have shown that zinc might inhibit its ribonucleic acid polymerase, that is the enzyme that allows the virus to replicate its RNA.

Vitamin C is an antioxidant that may play a role in our immune system’s ability to fight infection. In vitro and in vivo studies in chicks have shown that they could be protective against coronavirus. Human trials have found that it may decrease susceptibility to viral respiratory infections. When it comes to the common cold, there is limited evidence to suggest that high doses of oral vitamin C and zinc might reduce the duration of symptoms and decrease the severity of symptoms.

But what about zinc and vitamin C for the treatment of COVID19?

The COVID19 A to Z study was a prospective randomized clinical open-label trial at multiple hospitals within a single health system, involving sites in Ohio and Florida. Enrolled participants remained in their own home settings, and all study visits and/or procedures were conducted virtually via telephone, email, computer, or laptop. So, we are not talking about hospitalized COVID19 patients. We’re talking about patients with mild, perhaps moderate illness here. A total of 214 patients were randomized, 132 women, 82 men, and 45.

Patients were randomized in a 1:1:1:1 ratio, meaning 1/4th received vitamin C, 1/4th received zinc, 1/4th received both vitamin C and zinc, and 1/4th received neither, just standard of care, which is nothing more than rest, hydration, and maybe some Tylenol or ibuprofen, but no supplements. The vitamin C group received 10 days of 8,000 mg vitamin C after being diagnosed with COVID19 based on PCR testing. The zinc group received 50 mg of zinc gluconate at bedtime. The zinc and vitamin C group received 8,000 mg of vitamin C and 50 mg of zinc.

So, we are talking big doses here, much more than what most people take. Patients then tracked their symptoms daily, including potential side effects from vitamin c and zinc. During the course of study, patients admitted to the hospital were considered treatment failures and were no longer required to continue study supplementation or track their daily symptoms. The trial’s primary endpoint was the number of days required to reach a 50% reduction in symptom severity score from peak symptom score. Secondary endpoints were the number of days required to get a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of vitamin C and Zinc.

Based on statistical analysis, there was no significant difference in the primary outcome of days required to reach a 50% reduction in symptoms among the 4 study groups. Patients who received usual care without supplementation achieved a 50% reduction in symptoms on average 4.4 days compared with 3.7 for the vitamin C group, compared to 4.9 days for the zing group, and 3.4 days for the group that received both.

However, this study was not double-blind compared to a placebo study. That is, both patients and doctors knew what patients were receiving. We also do not know what the patients’ previous levels of vitamin C and zinc were. We also do not know what the patients’ vitamin D levels were, which plays a key role in the outcome of Covid-19. Finally, in this study patients received vitamin C orally at a dose of 8000 mg, while in a study vitamin C has been shown to be effective at a dose of 24,000 mg daily intravenously in patients with severe Covid-19.

In conclusion, this study does not meet the requirements of a serious scientific study and must be rejected.



  1. 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. https://pubmed.ncbi.nlm.nih.gov/33576820/ https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305
  2. Dimopoulos M. Intravenous vitamin C reduces COVID-19 deaths by two-thirds. Oct 15, 2020. https://mariosdimopoulos.com/epidimies/i-endoflevia-vitamini-c-meionei-tous-thanatous-apo-covid-19-sta-dio-trita/
  3. Zhang J, Rao X, Li Y, Zhu Y, Liu F, Guo F, Luo G, Meng Z, De Backer D, Xiang H, Peng Z-Y. (2020) High-dose vitamin C infusion for the treatment of critically ill COVID-19. Pulmonology, preprint. https://doi.org/10.21203/rs.3.rs-52778/v2


Marios Dimopoulos

Doctor of Naturopathy-Nutritionist-Author

PhD candidate in Integrative Medicine

Member of American Naturopathic Medical Association

Fellow of the American Council of Applied Clinical Nutrition

Member of the American Association of Drugless Practitioners

Member of the American Association of Nutritional Consultants

Member of the Canadian Association of Natural Nutritional Practitioners

Member of the Association for Natural Medicine in Europe

Member of the Society of Complementary Alternative and Holistic Practitioners

Member of the Pancyprian Association of Nutritionists

Member of the Professional Association of Complementary Medicine and Humanities

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