Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)
Medwave 2018 Jul-Ago;18(4):e7236 doi: 10.5867/medwave.2018.04.7236
Does vitamin C prevent the common cold?
Evelyn Gómez, Sebastián Quidel, Gonzalo Bravo-Soto, Ángela Ortigoza
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Abstract

INTRODUCTION
The common cold is one of the most common diseases. It is generally believed that the consumption of vitamin C prevents its appearance, but the actual efficacy of this measure is controversial.

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 eight systematic reviews including 45 studies overall, of which 31 were randomized trials. We concluded the consumption of vitamin C does not prevent the incidence of common cold.


 
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, etc. Despite the benign nature of this disease, it leads to a substantive economic burden in terms of medical consultation, treatment, and work or school absenteeism [1].

On the other hand, effective alternatives to prevent this condition are not available, and the efforts to develop a vaccine have been fruitless.

Vitamin C is usually perceived as an effective, harmless and inexpensive therapeutic alternative. Its use began in the early 30s and in the 70s it became widespread when the Nobel Prize winner, Linus Pauling, concluded that the use of vitamin C could prevent and relieve the common cold [1]. It is thought that vitamin C could improve the functioning of the immune system through various mechanisms [2]: phagocytes and lymphocytes concentrate vitamin C in levels up to 100 times higher than plasma, suggesting it has a role in the immune system; vitamin C increases the response of T lymphocytes and interferon levels.

However, although the effects on the immune system are well reported, it is not clear whether the intake of vitamin C for the prevention of the common cold translates into a clinically relevant benefit.

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 table of other considerations for decision-making. 

Key messages

  • The consumption of vitamin C does not prevent the incidence of common cold.
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We found eight systematic reviews [2],[3],[4],[5],[6],
[7],[8],[9] that  included 45 primary studies reported in 43 references [10],[11],[12],[13],[14],[15],[16],[17],
[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],
[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],
[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],
[51],[52], of which 31 corresponded to randomized controlled trials reported on 30 references [10],[11],
[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],
[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],
[32],[33],[34],[35],[36],[37],[38],[39].

Three trials [14],[33],[38] and the subgroups of five trials [10],[23],[30],[32],[37] were excluded from the analysis because they did not refer to our population of interest. We also excluded four trials [13],[15],[35],[39] that used low-dose vitamin C as a placebo.
This table and the summary in general are based on the relevant randomized trials. We excluded observational studies because they did not increase the certainty of the existing evidence or provide additional relevant information.

What types of patients were included*

The trials evaluated adults and children. Eighteen  trials [10],[12],[17],[18], [19],[20],[21],[22],[23],[24],[27],
[28],[29],[30],[32],[34],[36],[37] included adults and four trials included children [16],[25],[26],[31]. One trial [10] included participants between 14-64 years.

In general, the trials did not report the season when they were conducted and did not provide a clear definition of common cold, which is based on combination of symptoms such as nasal discharge, sore throat, lethargy and discomfort, with or without fever.

What types of interventions were included*

All trials evaluated supplementation with oral doses higher than 0.08 g/day of vitamin C.

Nine trials [10],[17],[18],[22],[31],[32],[34],[36],[37] administered low dose of vitamin C, in a range of 0.08 to 0.6 g/day. Ten trials 1 g/day [11],[12],[19],[20],[23],[25],[26],[28],[29],[30], four trials 2 g/day [16],[21],[24],[38] and one trial 3 g/day [27].
All trials compared against placebo.

What types of outcomes
were measured

The different trials measured multiple outcomes such, which were pooled by the systematic reviews as follows: incidence, duration and severity of the cold, among others.

The follow-up period ranged from 3 weeks to 36 weeks.

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

Summary of findings

The information of the effects of vitamin C in the prevention of common cold is based on 18 randomized trials [10],[12],[16],[17],[19],[20],[21],[22],[24],[25],[26],[28],[29],[30],[32],[34],[36],[37], which include 8472 patients in total. All trials measured the incidence of common cold during a specific time interval (8,472 patients).

The summary of findings is as follows: 

  • The consumption of vitamin C does not prevent the incidence of common cold. The certainty of the evidence is high.

Following 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

  • These results apply to healthy population in general, both adult and children.
    Although the trials did not evaluate patients with specific comorbidities, in the absence of direct evidence, it is reasonable to extrapolate this evidence to these populations.
  • This evidence does not apply to high performance athletes or other people subjected to major physical stress, since they are  considered a different population, in which the etiology of cold symptoms responds to other mechanisms, not related to viral contagion.
About the outcomes included in this summary
  • The outcome selected for the summary of findings table is the only one considered critical for decision-making according to the opinion of the authors of this summary, which agrees with the systematic reviews analyzed.
Balance between benefits and risks, and certainty of the evidence
  • Although it is an intervention that has none or minimal adverse effects,, as there is no benefit, the balance between benefits and risks is not favorable.
Resource considerations
  • Vitamin C is relatively inexpensive but has no benefit, so the balance between benefits and costs is not favorable.
  • From a population perspective, the expenses incurred to prevent the common cold by consuming vitamin C are large.
What would patients and their doctors think about this intervention
  • Faced with the evidence presented in this summary, both clinicians and patients should lean against using vitamin C for the prevention of the common cold.
  • However, it might be difficult to make patients desist from such deep-rooted preconceived ideas, even considering the certainty of the evidence. Therefore, variability in the decision-making is to be expected.
  • It is key for physicians to be reassured by scientific evidence in order to persuade their patients that this popular treatment offers no benefit.

Differences between this summary and other sources

  • The conclusions of this summary coincide with those of the systematic reviews identified.
  • These results agree with those reported in the American Family Physician guideline [53], which rely on the results of the Cochrane systematic review [4] to back their conclusions.
Could this evidence change in the future?
  • It is unlikely that the appearance of new evidence could modify the conclusions of this summary, due to the high certainty of the existing evidence.
  • In addition, we did not identify  ongoing randomized trials evaluating this question in the International Clinical Trials Registry Platform of the World Health Organization, or ongoing systematic reviews in PROSPERO database.
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 versionVitamina C for the prevention of 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 es una enfermedad muy frecuente. Existe la creencia que el consumo de vitamina C previene su aparición, pero la real eficacia de esta medida es controvertida.

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 ocho revisiones sistemáticas que en conjunto incluyen 45 estudios primarios, de los cuales 31 corresponden a ensayos aleatorizados. Concluimos que el consumo de vitamina C no previene la aparición del resfrío común.

Authors: Evelyn Gómez[1,2], Sebastián Quidel[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: Gómez E, Quidel S, Bravo-Soto GA, Ortigoza A. Does vitamin C prevent the common cold?. Medwave 2018 Jul-Ago;18(4):e7236 doi: 10.5867/medwave.2018.04.7236

Submission date: 13/3/2018

Acceptance date: 1/8/2018

Publication date: 6/8/2018

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

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

PubMed record

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Heikkinen T1, Järvinen A. The common cold. Lancet. 2003 Jan 4;361(9351):51-9.

Hemilä H. Vitamin C intake and susceptibility to the common cold. Br J Nutr. 1997 Jan;77(1):59-72. | PubMed |

Hemilä H. Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress. Int J Sports Med. 1996 Jul;17(5):379-83. | PubMed |

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

Hemilä H. Vitamin C supplementation and respiratory infections: a systematic review. Mil Med. 2004 Nov;169(11):920-5. Review. | 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. Review. | PubMed |

Pauling L. The significance of the evidence about ascorbic acid and the common cold. Proc Natl Acad Sci U S A. 1971 Nov;68(11):2678-81. Review. | PubMed | PMC |

Truswell S. Ascorbic Acid. New England Journal of Medicin. 1986

Peters EM, Goetzsche JM, Grobbelaar B, Noakes TD. Vitamin C supplementation reduces the incidence of postrace symptoms of upper-respiratory-tract infection in ultramarathon runners. Am J Clin Nutr. 1993 Feb;57(2):170-4. | PubMed |

Carr AB, Einstein R, Lai LY, Martin NG, Starmer GA. Vitamin C and the common cold: using identical twins as controls. Med J Aust. 1981 Oct 17;2(8):411-2. | PubMed |

Anderson TW, Reid DB, Beaton GH. Vitamin C and the common cold: a double-blind trial. Can Med Assoc J. 1972 Sep 23;107(6):503-8. | PubMed | PMC |

Miller JZ, Nance WE, Norton JA, Wolen RL, Griffith RS, Rose RJ. Therapeutic effect of vitamin C. A co-twin control study. JAMA. 1977 Jan 17;237(3):248-51. | PubMed |

RITZEL G. [Critical evaluation of vitamin C as a prophylactic and therapeutic agent in colds]. Helv Med Acta. 1961 Jan;28:63-8. German. | PubMed |

Ludvigsson J, Hansson LO, Tibbling G. Vitamin C as a preventive medicine against common colds in children. Scand J Infect Dis. 1977;9(2):91-8. | PubMed |

Bancalari A, Seguel C, Neira F, Ruíz I, Calvo C. [Prophylactic value of vitamin C in acute respiratory tract infections in schoolchildren]. Rev Med Chil. 1984 Sep;112(9):871-6. Spanish. | PubMed |

Baird IM, Hughes RE, Wilson HK, Davies JE, Howard AN. The effects of ascorbic acid and flavonoids on the occurrence of symptoms normally associated with the common cold. Am J Clin Nutr. 1979 Aug;32(8):1686-90. | PubMed |

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, Lee HP, St Leger AS, Baird M, Howard AN. A randomized controlled trial of vitamin C in the prevention and amelioration of the common cold. Br J Prev Soc Med. 1976 Sep;30(3):193-6. | PubMed | PMC |

Carson M, Corbett M, Cox H, Pollitt N. Letter: Vitamin C and the common cold. Br Med J. 1974 Mar 23;1(5907):577. | PubMed | PMC |

Liljefors I. [Vitamin C and the common cold]. Lakartidningen. 1972 Jul 5;69(28):3304-5. Swedish. | PubMed |

FRANZ WL, HEYL HL, SANDS GW. Blood ascorbic acid level in bioflavonoid and ascorbic acid therapy of common cold. J Am Med Assoc. 1956 Nov 24;162(13):1224-6. | PubMed |

Constantini NW, Dubnov-Raz G, Eyal BB, Berry EM, Cohen AH, Hemilä H. The effect of vitamin C on upper respiratory infections in adolescent swimmers: a randomized trial. Eur J Pediatr. 2011 Jan;170(1):59-63. | CrossRef | PubMed |

Pitt HA, Costrini AM. Vitamin C prophylaxis in marine recruits. JAMA. 1979 Mar 2;241(9):908-11. | PubMed |

Coulehan JL, Eberhard S, Kapner L, Taylor F, Rogers K, Garry P. Vitamin C and acute illness in Navajo school children. N Engl J Med. 1976 Oct 28;295(18):973-7. | PubMed |

Clegg KM, Macdonald JM. L-Ascorbic acid and D-isoascorbic acid in a common cold survey. Am J Clin Nutr. 1975 Sep;28(9):973-6. | PubMed |

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 |

Van Straten M, Josling P. Preventing the common cold with a vitamin C supplement: a double-blind, placebo-controlled survey. Adv Ther. 2002 May-Jun;19(3):151-9. | PubMed |

Himmelstein SA. The effect of vitamin C supplementation on incidence of upper respiratory tract infections in marathon runners [PhD Thesis; 163 pp]. Albuquerque, NM: University of New Mexico, 1996. | Link |

Wilson CW, Loh HS, Foster FG. The beneficial effect of vitamin C on the common cold. Eur J Clin Pharmacol. 1973 Jun;6(1):26-32. | PubMed |

Peters EM, Goetzsche JM, Joseph LE, Noakes TD. Vitamin C as effective as combinations of antioxidant nutrients in reducing symptoms of upper respiratory tract infection in ultramarathon runners. South African Journal of Sports Medicine 1996;11:23–7. | Link |

Sabiston B. H., Radomski M. W.: Health Problems and Vitamin in Canadian Northern Military Operations. DCIEM Report No. 74-R-W12. Downsview, Ontario, Defence Research Board, 1974. | Link |

Dahlberg G, Engel A, Rydin H. The value of ascorbic acid as a prophylactic against common colds. Acta Medica Scandinavica 1944;119:540–61. | Link |

Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S. Effect of vitamin C on common cold: randomized controlled trial. Eur J Clin Nutr. 2006 Jan;60(1):9-17. | PubMed |

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