Vitamin C Supplementation for the Treatment of COVID-19: A Systematic Review and Meta-Analysis

Abstract

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2), millions of people have died, and the medical system has faced significant difficulties. Our purpose was to perform a meta-analysis to estimate the effect of vitamin C on in-hospital mortality and the ICU or hospital length of stay for patients diagnosed with COVID-19. We conducted a systematic review with meta-analysis in the following databases: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials. We included studies that evaluated the effect of vitamin C supplementation, compared with standard treatment in COVID-19 patients who are ≥18 y of age. Nineteen trials were included in the meta-analysis. In-hospital mortality with and without vitamin C supplementation was 24.1% vs. 33.9% (OR = 0.59; 95%CI: 0.37 to 0.95; p = 0.03), respectively. Sub-analysis showed that, in randomized clinical trials, in-hospital mortality varied and amounted to 23.9% vs. 35.8% (OR = 0.44; 95%CI: 0.25 to 0.76; p = 0.003), respectively. In the non-randomized trials, in-hospital mortality was 24.2% vs. 33.5% (OR = 0.72; 95%CI: 0.38 to 1.39; p = 0.33), respectively. The ICU length of stay was longer in patients treated with vitamin C vs. standard therapy, 11.1 (7.3) vs. 8.3 (4.7) days (MD = 1.91; 95%CI: 0.89 to 2.93; p < 0.001), respectively. Acute kidney injury in patients treated with and without vitamin C varied and amounted to 27.8% vs. 45.0% (OR = 0.56; 95%CI: 0.40 to 0.78; p < 0.001), respectively. There were no differences in the frequency of other adverse events among patients’ treatment with and without vitamin C (all p > 0.05). The use of vitamin C reduces hospital mortality. The length of stay in the ICU is longer among patients treated with vitamin C. In terms of patient safety, vitamin C has an acceptable profile. Low doses of vitamin C are effective and safe. Despite some evidence of the usefulness of vitamin C in modifying the course of COVID-19, it is too early to modify guidelines and recommendations. Further studies, in particular randomized clinical trials, are necessary.

The Association Between Antioxidants and COVID-19 Outcomes: a Systematic Review on Observational Studies

“…Moreover, a systematic review and meta-analysis [ 47 ] demonstrated that antioxidants, especially Zn, and Se, vitamins C and D, improve COVID-19 clinical outcomes and reduce the severity. Another systematic review and meta-analysis [ 48 ] revealed that vitamin C supplementation reduces hospital mortality in COVID-19 patients, but ICU LOS and hospital LOS were longer in the patients who were treated with vitamin C.…”

“…Moreover, a systematic review and meta-analysis [47] demonstrated that antioxidants, especially Zn, and Se, vitamins C and D, improve COVID-19 clinical outcomes and reduce the severity. Another systematic review and meta-analysis [48] revealed that vitamin C supplementation reduces hospital mortality in COVID-19 patients, but ICU LOS and hospital LOS were longer in the patients who were treated with vitamin C. This observed inconsistency among included studies may be due to the following causes: (a) antioxidants were used as the primary treatment in certain investigations, while in others, they served as a co-adjuvant to formal experimental therapy. (b) The hospital setting (inpatient vs. outpatient) and ethnicity varied between studies.…”

Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A Revaluation of Pauling’s Vitamin C Therapy

“…There has recently been emerging evidence for the use of vitamin C as a treatment for sepsis [ 20 ]. Similarly, high-dose intravenous vitamin C (HDIVC) treatment has been reported to be effective in decreasing days of hospitalization, ICU stay and mortality in patients with COVID-19 [ 16 , 17 , 18 , 36 ]. Bypassing the limitations of vitamin C uptake through a sodium-dependent vitamin C transporter (SVCT1), HDVIC can achieve 70-fold higher plasma concentrations of vitamin C compared to oral administration [ 180 ].…”

“…It is likely that ascorbate therapy alone, or nitrate (or nitrite) therapy alone, may be insufficient to drive the reductive mechanism. A combination of these factors, as well as the appropriate mode of delivery (intravenous administration or oral administration), could be required to maximize the effects, which is a possible reason why HDIVC treatment in the ICU is sometimes ineffective or has effects opposite to our expectations [ 18 ].…”

“…It may be difficult to rely on a single drug or chemical to cure the disease. High-dose intravenous vitamin C (HDIVC) treatment has been reported to be effective in decreasing days of hospitalization, ICU stay and mortality [ 16 , 17 , 18 ]. Vitamin C therapy has been known for several decades to be a safe adjunctive treatment that has been examined for a wide variety of diseases, including severe acute respiratory syndrome (SARS) caused by SARS-CoV [ 19 ].…”