Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)
Medwave 2018;18(5):e7260 doi: 10.5867/medwave.2018.06.7260
What are the effects of vitamin C on the duration and severity of the common cold?
Sebastián Quidel, Evelyn Gómez, Gonzalo Bravo-Soto, Ángela Ortigoza
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Key Words: Vitamin C, common cold, Epistemonikos, GRADE.

Abstract

INTRODUCTION
The common cold causes great morbidity throughout the world and there are no effective therapeutic agents against it. There is a belief that consuming vitamin C during a cold episode would help reduce duration and severity of symptoms. However, there is controversy about this claim.

METHODS
To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.

RESULTS AND CONCLUSIONS
We identified four systematic reviews that included eight primary studies overall, of which seven were randomized trials. We concluded vitamin C has minimal or no impact on the duration of common cold or in the number of days at home or out of work.


 
Problem

The common cold is one of the most common diseases in the general population. The term ‘common cold’ does not refer to a specific condition, but to a group of symptoms such as nasal obstruction, sore throat, cough, lethargy and asthenia, with or without fever. These symptoms have multiple etiological agents such as rhinovirus, adenovirus, syncytial virus, among others. Despite the benign nature of this condition, it leads to substantial economic burden in terms of medical consultation, treatment, and work or school absenteeism [1].
Antibiotics have no role in the treatment of the common cold, even though they are widely prescribed and used. The development of a vaccine has been elusive since this condition is caused by multiple agents. Considering the prevalence of this disease, and the associated morbidity and costs, any intervention that can shorten the symptomatic period would constitute an important public health advance.
At the population level, it is widely believed that consuming vitamin C helps alleviate symptoms of the common cold. However, there is controversy about the scientific support to this belief.

Methods

To answer the question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others, to identify systematic reviews and their included primary studies. We extracted data from the identified reviews and reanalyzed data from primary studies included in those reviews. With this information, we generated a structured summary denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos) using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies when it is possible, a summary of findings table following the GRADE approach and a section of other considerations for decision-making. 

Key messages

  • Vitamin C has little or no impact on the duration of the cold and on days at home or out of work.
  • Despite the lack of relevant adverse effects, investing in this treatment is not justified.
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We found four systematic reviews [2],[3],[4],[5] that included eight primary studies [6],[7],[8],[9],[10],[11],[12],[13] of which, seven were randomized trials [6],[7],[8],[9],[10],[11],[12]. This table and the summary in general are based on the latter, since the observational study did not increase the certainty of the existing evidence, or provide additional relevant information.

What types of patients were included*

Four trials included patients of both sexes [7],[8],[11],[12], one only included women [9] and two did not specify it [6],[10].

Six trials included adults[6],[7],[8],[9],[11],[12] and one did not specify it [10].

The trials were conducted in Canada [6],[7], the United States [5],[9], the United Kingdom [8],[10] and Australia [11].

What types of interventions were included*

All the trials evaluated vitamin C administered in different doses, starting the first day of cold. 

All the trials compared against placebo, and two of them also evaluated the effectiveness of vitamin C by comparing different doses: 4 or 8 grams [7] and 1 or 3 grams [12].

The dose and duration of the treatment varied in all the studies: 3 grams per day for 5 days [6], 4 or 8 grams per day for one day [7], 1 gram per day for 5 days [8] , 4 grams per day for 2.5 days [9],[11], 3 grams per day for 2 days [10] and 1 or 3 grams per day for 3 days [12].

What types of outcomes
were measured

The measurement method for the duration of the cold was very heterogeneous among the included trials, so, in order to standardize the results, the systematic review that included more trials [2] decided to report the duration in the form of percentages (being placebo equivalent to a 100%). To facilitate interpretation, these percentages were converted into absolute numbers according to the average number of days of symptoms in the trials.

The severity was also measured heterogeneously in the different trials. The reviews pooled the results as days at home or out of work, or with a symptom score.

* The information about primary studies is extracted from the systematic reviews identified, unless otherwise specified.

Summary of findings

The information on the effects of vitamin C for the common cold is based on seven randomized trials including 3249 patients [6],[7],[8],[9],[10],[11],[12].
All trials reported the duration of the cold (3249 patients) and three trials [7],[8],[11] reported days at home or out of work (2569 patients).

The summary of findings is as follows:

  • Vitamin C has little or no impact on the duration of the cold. The certainty of the evidence is high.
  • Vitamin C has little or no impact on days at home or out of work. The certainty of the evidence is high.

Follow the link to access the interactive version of this table (Interactive Summary of Findings – iSoF)

Other considerations for decision-making

To whom this evidence does and does not apply

  • The results of this summary are widely applicable to people with the common cold, regardless of gender or race. Even though the participants in the trials did not include children, pregnant women, groups with comorbidities or people subjected to high physical stress or extreme cold, there are no compelling clinical reasons for not applying the evidence to these groups.
  • All of the included trials were conducted in Anglo-Saxon countries with temperate climates, however, there are no clinical or pathophysiological reasons for not applying the results to different geographic locations or climates. Therefore, in the absence of direct evidence in these contexts, it is reasonable to extrapolate the results of this summary to any person with the common cold.
About the outcomes included in this summary
  • The outcomes selected are those considered critical for decision-making based on the opinion of the authors of this summary, and are in agreement with those presented by the main systematic reviews identified.
Balance between benefits and risks, and certainty of the evidence
  • None of the systematic reviews conducted a meta-analysis of the adverse effects. One of the systematic reviews [2] delved into the topic reporting that seven studies (not specified) recorded data from a total of 2,490 patients who had used ≥ 1 g/day of vitamin C compared to 2066 who took placebo. In total, 5.8% of patients who received vitamin C had adverse effects (not detailed) that could be attributed to the medication, compared to 6.0% of those who took placebo. No serious adverse effects were reported.
  • Even though it is an intervention with minimal adverse effects, it has no benefit, so the balance between benefits and risks is not favorable.
Resource considerations
  • Notwithstanding vitamin C is easy to acquire and relatively inexpensive, it has no benefits, so the balance between benefits and costs is not favorable.
What would patients and their doctors think about this intervention
  • Faced with the evidence presented in this summary, most patients and doctors should lean against using this intervention.
  • However, as the belief in the efficacy of vitamin C is deeply rooted in the general population, additional efforts are probably needed to get the message across.

Differences between this summary and other sources

  • The conclusions presented are consistent with the main systematic review [2] and are also in agreement with the guideline ‘The Common Cold’ [1].
Could this evidence change in the future?
  • The probability that future studies change the conclusion of this summary is very low, since the certainty of the evidence is high.
  • We did not identify ongoing trials addressing this question in the International Clinical Trials Registry Platform of the World Health Organization or systematic reviews in progress in the PROSPERO registry.
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Vitamin C for the treatment of the common cold

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier.

After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

This article is part of the Epistemonikos Evidence Synthesis project. It is elaborated with a pre-established methodology, following rigorous methodological standards and internal peer review process. Each of these articles corresponds to a summary, denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos), whose main objective is to synthesize the body of evidence for a specific question, with a friendly format to clinical professionals. Its main resources are based on the evidence matrix of Epistemonikos and analysis of results using GRADE methodology. Further details of the methods for developing this FRISBEE are described here (http://dx.doi.org/10.5867/medwave.2014.06.5997)

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

Potential conflicts of interest

The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

INTRODUCCIÓN
El resfrío común causa una gran morbilidad en todo el mundo y no se cuenta con agentes terapéuticos eficaces contra éste. Existe la creencia de que ingerir vitamina C durante un episodio de resfrío ayuda a disminuir la duración y severidad de los síntomas, sin embargo existe controversia respecto a esta afirmación.

MÉTODOS
Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE.

RESULTADOS Y CONCLUSIONES
Identificamos cuatro revisiones sistemáticas que en conjunto incluyeron ocho estudios primarios, de los cuales siete son ensayos aleatorizados. Concluimos que la vitamina C tiene un impacto mínimo o nulo en la duración del resfrío y en los días en casa o sin trabajar.

Authors: Sebastián Quidel[1,2], Evelyn Gómez[1,2], Gonzalo Bravo-Soto[2,4], Ángela Ortigoza[2,3]

Affiliation:
[1] Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[2] Proyecto Epistemonikos, Santiago, Chile
[3] Departamento de Medicina Familiar, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[4] Centro Evidencia UC, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

E-mail: acortigoza@uc.cl

Author address:
[1] Centro Evidencia UC
Pontificia Universidad Católica de Chile
Diagonal Paraguay 476
Santiago
Chile

Citation: Quidel S, Gómez E, Bravo-Soto GA, Ortigoza A. What are the effects of vitamin C on the duration and severity of the common cold?. Medwave 2018;18(5):e7260 doi: 10.5867/medwave.2018.06.7260

Submission date: 18/3/2018

Acceptance date: 4/9/2018

Publication date: 3/10/2018

Origin: This article is a product of the Evidence Synthesis Project of Epistemonikos Fundation, in collaboration with Medwave for its publication.

Type of review: Non-blinded peer review by members of the methodological team of Epistemonikos Evidence Synthesis Project.

PubMed record

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  1. Heikkinen T1, Järvinen A. The common cold. Lancet. 2003 Jan 4;361(9351):51-9.
  2. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD000980. | CrossRef | PubMed |
  3. Chalmers TC. Effects of ascorbic acid on the common cold. An evaluation of the evidence. Am J Med. 1975 Apr;58(4):532-6. | PubMed |
  4. Hemilä H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hypotheses. 1999 Feb;52(2):171-8. | PubMed |
  5. Truswell S. Absorbic acid. N Eng J Med. 1986 Sep; 315:708-710. | CrossRef |
  6. Karlowski TR, Chalmers TC, Frenkel LD, Kapikian AZ, Lewis TL, Lynch JM. Ascorbic acid for the common cold. A prophylactic and therapeutic trial. JAMA. 1975 Mar 10;231(10):1038-42. | PubMed |
  7. Anderson TW, Suranyi G, Beaton GH. The effect on winter illness of large doses of vitamin C. Can Med Assoc J. 1974 Jul 6;111(1):31-6. | PubMed | PMC |
  8. Anderson TW, Beaton GH, Corey P, Spero L. Winter illness and vitamin C: the effect of relatively low doses. Can Med Assoc J. 1975 Apr 5;112(7):823-6. | PubMed | PMC |
  9. Elwood PC, Hughes SJ, Leger AS. A randomized controlled trial of the therapeutic effect of vitamin C in the common cold. Practitioner. 1977 Jan;218(1303):133-7. | PubMed |
  10. COWAN DW, DIEHL HS. Antihistaminic agents and ascorbic acid in the early treatment of the common cold. J Am Med Assoc. 1950 Jun 3;143(5):421-4. | PubMed |
  11. Tyrrell DA, Craig JW, Meada TW, White T. A trial of ascorbic acid in the treatment of the common cold. Br J Prev Soc Med. 1977 Sep;31(3):189-91. | PubMed | PMC |
  12. Audera C, Patulny RV, Sander BH, Douglas RM. Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial. Med J Aust. 2001 Oct 1;175(7):359-62. | PubMed |
  13. Glazebrook AJ, Thomson S. The administration of vitamin C in a large institution and its effect on general health and resistance to infection. J Hyg (Lond). 1942 Jan;42(1):1-19. | PubMed | PMC |
Heikkinen T1, Järvinen A. The common cold. Lancet. 2003 Jan 4;361(9351):51-9.

Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD000980. | CrossRef | PubMed |

Chalmers TC. Effects of ascorbic acid on the common cold. An evaluation of the evidence. Am J Med. 1975 Apr;58(4):532-6. | PubMed |

Hemilä H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hypotheses. 1999 Feb;52(2):171-8. | PubMed |

Truswell S. Absorbic acid. N Eng J Med. 1986 Sep; 315:708-710. | CrossRef |

Karlowski TR, Chalmers TC, Frenkel LD, Kapikian AZ, Lewis TL, Lynch JM. Ascorbic acid for the common cold. A prophylactic and therapeutic trial. JAMA. 1975 Mar 10;231(10):1038-42. | PubMed |

Anderson TW, Suranyi G, Beaton GH. The effect on winter illness of large doses of vitamin C. Can Med Assoc J. 1974 Jul 6;111(1):31-6. | PubMed | PMC |

Anderson TW, Beaton GH, Corey P, Spero L. Winter illness and vitamin C: the effect of relatively low doses. Can Med Assoc J. 1975 Apr 5;112(7):823-6. | PubMed | PMC |

Elwood PC, Hughes SJ, Leger AS. A randomized controlled trial of the therapeutic effect of vitamin C in the common cold. Practitioner. 1977 Jan;218(1303):133-7. | PubMed |

COWAN DW, DIEHL HS. Antihistaminic agents and ascorbic acid in the early treatment of the common cold. J Am Med Assoc. 1950 Jun 3;143(5):421-4. | PubMed |

Tyrrell DA, Craig JW, Meada TW, White T. A trial of ascorbic acid in the treatment of the common cold. Br J Prev Soc Med. 1977 Sep;31(3):189-91. | PubMed | PMC |

Audera C, Patulny RV, Sander BH, Douglas RM. Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial. Med J Aust. 2001 Oct 1;175(7):359-62. | PubMed |

Glazebrook AJ, Thomson S. The administration of vitamin C in a large institution and its effect on general health and resistance to infection. J Hyg (Lond). 1942 Jan;42(1):1-19. | PubMed | PMC |