key: cord-0700341-8h5scczb
authors: Schloss, Janet; Lauche, Romy; Harnett, Joanne; Hannan, Nicole; Brown, Danielle; Greenfield, Tom; Steel, Amie
title: Rapid review of Systematic reviews on the efficacy and safety of Vitamin C in the management of Acute Respiratory Infection and Disease: Authors
date: 2020-07-31
journal: Adv Integr Med
DOI: 10.1016/j.aimed.2020.07.008
sha: 3bf76b8ba88a524fb5b6f2987e33e09e513e2a0b
doc_id: 700341
cord_uid: 8h5scczb

Brief overview Current evidence from published systematic reviews indicate that oral intake of vitamin C may assist with symptoms of acute viral respiratory infections (ARI) by reducing fever and chills, relieving chest pain and assist in reducing symptoms of common cold-induced asthma. Intravenous (IV) vitamin C administration may reduce the need for vasopressor support and the duration of mechanical ventilations in critically ill patients in hospital. COVID-19 has similar signs and symptoms of ARI. Further studies involving patients with COVID-19, either through administration of oral vitamin C in mild cases or IV vitamin C in critical cases, would be advantageous to examine if it is safe and efficacious. Verdict Oral vitamin C may assist with the symptoms of acute respiratory viral infections (ARI) and common cold-induced asthma but no studies have been identified justifying oral vitamin C for the prevention or treatment of coronavirus infections including COVID-19. When taken at onset of ARI, oral vitamin C may reduce the duration of symptoms including fever, chest pain, chills and bodily aches and pains. It may also reduce the incidence of hospital admission and duration of hospital stays. For individuals admitted to hospital with community-acquired pneumonia, vitamin C may improve respiratory function in more severe cases. No major adverse events nor interactions were reported by either method of administration. However, there is an absence of high quality, contemporary clinical research examining this topic. Current evidence suggests further studies are needed to better understand the value of both oral and IV vitamin C for ARI, including COVID-19.

Current evidence from published systematic reviews indicate that oral intake of vitamin C may assist with symptoms of acute viral respiratory infections (ARI) by reducing fever and chills, relieving chest pain and assist in reducing symptoms of common cold-induced asthma. Intravenous (IV) vitamin C administration may reduce the need for vasopressor support and the duration of mechanical ventilations in critically ill patients in hospital. COVID-19 has similar signs and symptoms of ARI.

Further studies involving patients with COVID-19, either through administration of oral vitamin C in mild cases or IV vitamin C in critical cases, would be advantageous to examine if it is safe and efficacious.

Oral vitamin C may assist with the symptoms of acute respiratory viral infections (ARI) and common cold-induced asthma but no studies have been identified justifying oral vitamin C for the prevention or treatment of coronavirus infections including COVID-19. When taken at onset of ARI, oral vitamin C may reduce the duration of symptoms including fever, chest pain, chills and bodily aches and pains. It may also reduce the incidence of hospital admission and duration of hospital stays. For individuals admitted to hospital with community-acquired pneumonia, vitamin C may improve respiratory function in more severe cases. No major adverse events nor interactions were reported by either method of administration. However, there is an absence of high quality, contemporary clinical research examining this topic. Current evidence suggests further studies are needed to better understand the value of both oral and IV vitamin C for ARI, including COVID-19.

J o u r n a l P r e -p r o o f Background Vitamin C is an essential micronutrient involved in various cellular functions of both the innate and adaptive immune systems. Vitamin C accumulates in phagocytic cells, such as neutrophils, through which it can enhance chemotaxis, phagocytosis, and generation of reactive oxygen species. Vitamin C is also involved with apoptosis and clearance of used neutrophils from sites of infection by macrophages thereby reducing potential tissue damage. Vitamin C also supports differentiation and proliferation of B-and T-cells. [1] .

Vitamin C was proposed as a potential useful agent for coronaviruses in 2003 when the SARS coronavirus was active [2] based on available evidence that vitamin C affects severe viral respiratory tract infections. Hemila [2] , who has continued researching vitamin C for ARI, presented this hypothesis based on the evidence of vitamin C's non-specific effects on severe viral respiratory tract infections. This raises queries regarding vitamin C's potential application in the management of COVID-19.

What is the effect of Vitamin C on acute respiratory tract infections in adults when administered at the onset of symptoms? 

Ovid Medline (Systematic Review/ or Meta-analysis/ or Systematic Review as Topic/ or Meta-Analysis as Topic/ or common cold or (respiratory adj2 (infect* or illness or symptom* or acute or virus* or disease))).ti,ab,kw. AND exp Ascorbic Acid/ or (ascorbic acid or Vitamin c).ti,ab,kw.

PT systematic review OR PT meta-analysis or (MH "Systematic Review") OR "systematic review" OR (MH "Cochrane Library") OR (MH "Meta Analysis") OR TX meta analy* OR TX metaanaly* OR TX systematic* review AND (MH "Influenza+") OR "Influenza" OR (MH "Influenza A Virus+") OR (MH virus* OR disease*)) AND (MH "Ascorbic Acid") OR TX "vitamin c" OR TX "Ascorbid adic"

The critical appraisal tool used to assess the studies in this rapid review was the BMJ Best practice, appraising systematic reviews (https://bestpractice.bmj.com/info/toolkit/learn-ebm/appraisingsystematic-reviews/).

A search conducted across 4 databases identified 141 review articles. Following the removal of 34 duplicates, 107 review articles were screened by title and abstract for relevance to the study question. Of these, 36 full-text literature reviews were assessed for eligibility against the pre-defined inclusion criteria. A total of 31 articles were removed due to not meeting one or more of the criteria as follows: different patient population (4), study design (14), intervention type (3), not an adult population (3), study setting (1), not written in English (1), indication (2), reviews of reviews (3), the remaining 6 articles were included in this rapid review.

From the appraisal, three of the five systematic reviews met all the requirements [4, 5, 7] . One systematic review met the majority of the requirements with the reviewers unable to verify if combined primary studies and combined statistical results were correct [6] . The last review was considered to have a lower level of evidence for a systematic review but was still adequate [3] .

Overall, the level of evidence for the reviews chosen were adequate.

J o u r n a l P r e -p r o o f

All five studies were systematic reviews of randomised controlled trials (RCTs) (Hemilä 2004 

The evidence from this rapid review has identified that oral vitamin C may assist with the symptoms of acute respiratory viral infections (ARI) and common cold-induced asthma but no studies have been identified justifying oral vitamin C for the prevention or treatment of conditions similar to COVID-19. When taken at onset of ARI, oral vitamin C may reduce the duration of AR symptoms including fever, chest pain, chills and bodily aches and pains. It may also reduce the incidence of hospital admission and duration of hospital stays. Evidence related to IV vitamin C from this literature review for COVID-19 or similar conditions is very limited due to the reviews not specifying IV versus oral administration. However, from the studies included in these reviews, further investigation is warranted to examine the effect of IV vitamin C as an adjunct to current medical treatment in acute COVID-19 patients. In addition, oral administration at onset of symptoms to reduce duration and severity of COVID-19 infection also warrants further investigation. Current 

Vitamin C and Immune Function

Vitamin C supplementation and respiratory infections: a systematic review

Vitamin C and common cold-induced asthma: a systematic review and statistical analysis

Vitamin C for preventing and treating the common cold

Vitamin C for preventing and treating pneumonia Review

Extra dose of vitamin C based on a daily supplementation shortens the common cold: A meta-analysis of 9 randomized controlled trials