Since the days of Linus Pauling, much has been written about the role of vitamin C in managing or preventing infections. So too, with COVID-19, interest has focused on the use of this supplement to mitigate the devastating effects of the coronavirus. 

It has been hypothesized that vitamin C may have anti-inflammatory or antioxidant effects in this infectious disease. However, much of the information that has been published is anecdotal and lacks statistical significance, which makes it difficult to assess clinical relevance. A small, uncontrolled trial of 18 patients from Spain with SARS-CoV2 acute respiratory distress syndrome found that 90% of those studied had undetectable vitamin C levels. They postulated that increased metabolic demand, glomerular hyperfiltration, renal replacement, alterations in gastrointestinal absorption, and decreased recycling of dehydroascorbate to ascorbic acid are possible mechanisms to explain this finding. 

Data were analyzed from a case series of 17 patients from Philadelphia with confirmed SAR-CoV-2 who required >30% fraction of inspired oxygen and who received IV vitamin C 1 gram every 8 hours for 3 days as part of a COVID-19 treatment protocol. Other drugs in the COVID-19 treatment regimen included hydroxychloroquine, methylprednisolone, and/or tocilizumab. 

Vitamin C was initiated a mean of 3 days postadmission. Twelve percent of patients died; 18% had been intubated. After vitamin C administration, patients had significantly lower D-dimer and ferritin levels, which demonstrated reduced markers of inflammation. 

A recent living systematic review by the COVID-19 L-OVE (Living Overview of Evidence) investigators was designed to provide a timely and vigorous updated summary of the available evidence on the use of vitamin C in treating patients infected by SAR-CoV2. (A living systematic review is a systematic review that is continually updated to reflect relevant new evidence as it becomes available.)

Researchers searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, grey literature, and a centralized repository in L-OVE for randomized clinical trials on the effects of vitamin C in patients with COVID-19. The Epistemonikos database, a collaborative, multilingual database of health evidence that is the largest source of systematic reviews relevant for health decision-making and a large source of other types of scientific evidence, was searched for studies on vitamin C and COVID-19. Thirty-four trial registries, preprint servers, and websites specializing in COVID-19 were analyzed. Animal and in vitro data were excluded. The inclusion criteria (besides study type) were unrestrictive and included any study as long as the participants were defined by the authors of the trial and vitamin C was the intervention of interest. The primary outcome was all-cause mortality. 

The investigators retrieved a total of 95 records; however, none of the studies met the minimum requirements to inform clinical decisions, which speaks to the difficulty of conducting research during a lethal pandemic. The investigators also identified 20 ongoing studies, including 13 randomized trials and seven nonrandomized studies. 

The researchers concluded that after the most extensive and robust review on the use of vitamin C in COVID-10, there is no evidence to support or refute the use of vitamin C in the treatment of COVID-19. They caution that it may be the short time since the discovery of SARS-CoV2 that has not allowed for high-quality research. In support of this study, the authors cite that their living systematic review may combat some of the shortcomings in the use of rapid review methods, which are designed to quickly disseminate information at the expense of clinical vetting. 

One trial that may help answer the question of what is the role of vitamin C in COVID-19 is a randomized, controlled trial  being conducted in China that is exploring the use of high-dose (12 g) vitamin C administered IV every 12 hours to 140 patients aged 18 years or older diagnosed with serious or critical SARS-CoV2 infection and who are being treated in the ICU. Results from this trial are expected this Fall. 

It is important to keep in mind that while vitamin C is a water-soluble vitamin and is relatively nontoxic, adverse events can be associated with large amounts of the drug. Clinicians from Italy report on two patients with COVID-19 treated with high-dose vitamin C (50 mg/kg four times a day) who developed oxalate nephropathy. This renal disease was thought to be secondary to the high-dose vitamin C administration, although many confounding factors were present. 

Pharmacists have a duty to dispel healthcare misinformation, which is rampant in the digital era. These papers help to clarify the role of vitamin C in the treatment of COVID-19 and provide pharmacists with the information that they need in counseling patients or other healthcare professionals.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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