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High-dose vitamin C intravenous infusion in the treatment of patients with COVID-19

A protocol for systematic review and meta-analysis

Lifang Huang, MB,aLang Wang, MB,aJianghong Tan, MB,bHong Liu, MB,a and Yanhui Ni, MBc

Published online 2021 May 14


Patients infected with a virus usually lack vitamin C. High-dose vitamin C has an antiviral effect, and has been used by several researchers to treat COVID-19 by intravenous infusion, achieving good results. However, the efficacy and safety of vitamin C in the treatment of patients with COVID-19 remain unclear. Thus, the aim of the present study was to investigate the efficacy of high-dose vitamin C infusion in the treatment of patients with COVID-19.


The outbreak of the novel coronavirus (COVID-19) began in December 2019, and remains a prevalent threat around the world. COVID-19 is highly infectious and has high mortality, especially in patients with underlying health issues (such as diabetes).[1] At present, there is no specific drug for the treatment of COVID-19, and many potential therapeutic drugs have been included in the scope of clinical trials. Several institutions have focused on verifying the therapeutic effect of vitamin C on COVID-19.[2,3]

Also known as L-ascorbic acid, vitamin C is a kind of water-soluble vitamin that exists in blood and cells in the form of reduced ascorbic acid. Clinically, vitamin C is mainly used for the treatment of scurvy, and also for the adjuvant treatment of various acute and chronic infectious diseases.[4] Vitamin C is an essential vitamin for human immune system, which can enhance the body's immunity to viruses in a number of ways. High concentration of vitamin C can enhance the antiviral ability, especially in the form of dehydroascorbic acid, which can inhibit influenza A virus.[4,5] As revealed by prior research, vitamin C has a strong antiviral effect only in large doses,[6] and serum vitamin C levels are low in most critically ill patients with COVID-19.[7,8] Hence, the use of high-dose vitamin C in the treatment of patients with COVID-19 is certainly feasible.

Despite the feasibility, there is a scarcity of high-quality evidence to support the efficacy and safety of high-dose vitamin C in patients with COVID-19. For this reason, in the present study, the efficacy of vitamin C therapy was systematically evaluated, so as to provide evidence-based guidance for clinical application.

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Vitamin C has been extensively applied in the treatment of viral infections, with studies revealing that patients with pneumonia and sepsis have low levels of vitamin C and elevated oxidative stress.[13] Owing to the direct inhibitory effect thereof on pathogens, there is sufficient evidence to suggest that vitamin C is effective in the treatment of pneumonia and infection.[14] Further, vitamin C has been shown to reduce the severity and duration of pneumonia,[15] while meta-analysis of 12 trials in 1766 patients calculated that vitamin C reduced ICU stay by an average of 8%.[16] Another meta-analysis found that vitamin C reduced the duration of mechanical ventilation in ICU patients.[17] Novel coronavirus pneumonia is a new respiratory disease caused by COVID-19, and is severely infectious.[18] Thus, vitamin C novel coronavirus pneumonia can also be applied to the treatment of patients.

Vitamin C can improve the resistance of white blood cells to viruses, has an antioxidant effect, and can induce interferon production in vivo.[4,19]

In viral infections, vitamin C can attenuate pro-inflammatory response, enhance epithelial barrier function, increase alveolar fluid clearance rate, and prevent sepsis related coagulation abnormalities.[20] The implementation of high-dose vitamin C treatment can significantly reduce the demand for high-dose corticosteroids, antibiotics, and antiviral drugs, as these drugs may have the effects of immunosuppression, adrenal suppression and toxicity, complicating the course of the disease.[21] Combined with traditional Chinese medicine, Yali used a large dose of vitamin C (20 g/60 kg per day) to treat COVID-19.[22] As a result of Yali treatment, the symptoms of fatigue, cough, dry throat, and shortness of breath were significantly improved, and no adverse events occurred.[22] Zhang used a large dose of vitamin C (24 g/day) at the rate of 12 mL/h to treat patients with COVID-19,[23] with the results revealing that the PaO2/FiO2 of patients increased steadily, and the 28 day mortality of patients decreased significantly.[23] Therefore, high-dose vitamin C infusion may be a significantly effective therapeutic agent in COVID-19 treatment.

Since there is currently a scarcity of related research, whether high-dose vitamin C can improve the prognosis of patients with COVID-19 is yet to be ascertained, and is a high-priority concern for medical scholars. The present study is the first systematic review and meta-analysis of the efficacy of high-dose vitamin C in patients with COVID-19. Notably, the lack of adequate randomized controlled trials could be regarded as a limitation of the present meta-analysis.

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