P (population, patient, problem)

I (intervention)

C (comparison)

O (outcome)

Adults

Zinc

Supportive Care

Incidence

Children

Vitamin C

Standard Care

Duration

General population

Supplement

Antiviral/antibiotics

Severity

Supplementation

Vaccines

Side effects

No Intervention

Placebo

Terms Used:

Zinc, zinc supplement, common cold

Databases/

Other Tools:

-UpToDate

-PubMed

# of Articles Returned:

Indirectly taken from UpToDate to PubMed from the reference section of article “The common cold in adults: Treatment and prevention”

Why these articles?

Zinc Lozenges May Shorten the Duration of Colds: A Systematic Review

This is a systematic review that concentrated specifically on one medium of zinc, zinc lozenges, and its therapeutic effect on natural common colds. The article was published in 2011 in a peer reviewed, open access journal Bentham OPEN. The review did not exclude non-randomized trials, but the 13 trials they did select, coinsidently were double-blind randomized control trials.

Terms Used:

Zinc, zinc supplementation, common cold, cold prevention

Databases/

Other Tools:

UpToDate

Pubmed

Wiley Online Library

# of Articles Returned:

38

Why these

articles?

The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in children

Article is a randomized controlled trial, with a population of n=200, published 12 years ago (revised in 2006).  Published in a peer reviewed medical journal Acta Paediatrica,, on Wiley Online Library; a credible evidence based database designed for healthcare professionals.

Terms Used:

zinc vitamin C supplement cold prevention

Databases/

Other Tools:

PubMed

Cochrane

# of Articles Returned:

9

Why these

articles?

Complementary and alternative medicine for prevention and treatment of the common cold (2011)                                                                                                            This is a systematic review that looks a variety of variables in the prevention of the common cold. It specifically looks into Zinc and Vitamin C supplements separately, and it is a recent review. The Review looks at 30 trials regarding the use of Zinc as treatment or preventions, and 38 trials regarding the use of Vitamin C as treatment or prevention. It is valuable as it addressed the use of both as treatment and as preventions.

Terms Used:

Zinc, common cold prevention and/or treatment

Databases/

Other Tools:

PubMed

Cochraine

# of Articles Returned:

11

Why these

articles?

Zinc for the treatment of common cold: a systematic review and meta-analysis of randomized controlled trials (2012).

This article is a systematic review and meta-analysis of RCTs that included 17 trials with total 2121 participants. This study compared results of orally administered zinc to placebo or no treatment to evaluate the efficacy and safety of zinc in treatment of common cold. It is taken from reputable peer-review journal CMAJ that has been continuously published since 1911.

Terms Used:

Vitamin C, Zinc, supplements, prevention of common cold

Databases/

Other Tools:

Cochrane Reviews, PubMed, Trip Database

# of Articles Returned:

Cochrane Reviews (53), PubMed (Initial search: 57877, filters: 135), Trip Database (2,978)

Why these

articles?

Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews

2013, Issue 1. Art. No.: CD000980. DOI: 10.1002/14651858.CD000980.pub4.

This is a meta-analysis study of  twenty-nine trial comparisons involving 11,306 participants. The majority of the included studies consisted of randomized controlled trials and double blinded. The meta-analysis examined the effects of Vitamin C supplementation on the incidence, the duration and severity of common cold. There was an independent assessment of risk bias in all included studies.

Name

Fauzia Bagum

Title

Zinc Lozenges May Shorten the Duration of Colds: A Systematic Review

Link

https://www-ncbi-nlm-nih-gov.york.ezproxy.cuny.edu/pmc/articles/PMC3136969/

Abstract

Background: A number of controlled trials have examined the effect of zinc lozenges on the common cold but the findings have diverged. The purpose of this study was to examine whether the total daily dose of zinc might explain part of the variation in the results.

Methods: The Medline, Scopus and Cochrane Central Register of Controlled Trials databases were searched for placebo-controlled trials examining the effect of zinc lozenges on common cold duration. Two methods were used for analysis: the P-values of the trials were combined by using the Fisher method and the results of the trials were pooled by using the inverse-variance method. Both approaches were used for all the identified trials and separately for the low zinc dose and the high zinc dose trials.

Results:Thirteen placebo-controlled comparisons have examined the therapeutic effect of zinc lozenges on common cold episodes of natural origin. Five of the trials used a total daily zinc dose of less than 75 mg and uniformly found no effect. Three trials used zinc acetate in daily doses of over 75 mg, the pooled result indicating a 42% reduction in the duration of colds (95% CI: 35% to 48%). Five trials used zinc salts other than acetate in daily doses of over 75 mg, the pooled result indicating a 20% reduction in the duration of colds (95% CI: 12% to 28%).

Conclusions: This study shows strong evidence that the zinc lozenge effect on common cold duration is heterogeneous so that benefit is observed with high doses of zinc but not with low doses. The effects of zinc lozenges should be further studied to determine the optimal lozenge compositions and treatment strategies.

Keywords: Meta-analysis, randomized controlled trials, respiratory infections, zinc.

Name

Lauren Feinstein

Title

The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in children

Link

https://www.ncbi.nlm.nih.gov/pubmed/16982486

Abstract

AIM:

To determine the efficacy of prophylactic administration of zinc sulphate in reducing the occurrence of the common cold in children, and to evaluate the efficacy of zinc sulphate in reducing the duration and severity of cold symptoms.

METHODS:

A total of 200 healthy children were randomly assigned to receive oral zinc sulphate (zinc group, n=100) or placebo (placebo group, n=100). Zinc sulphate (15 mg of zinc) or placebo syrup were administered for prophylaxis once daily during a 7-mo study period. The dose was increased to two times per day (30 mg of zinc) at the onset of cold, until symptoms resolved.

RESULTS:

The mean number of colds in the zinc group was significantly less than in the placebo group (1.2 vs 1.7 colds per child; p=0.003). The mean cold-related school absence was 0.9 d per child in the zinc group versus 1.3 d in the placebo group (p=0.04). Compared to the placebo group, the zinc group had shorter mean duration of cold symptoms and decreased total severity scores for cold symptoms (p<0.0001). Adverse effects were mild and similar in both groups.

CONCLUSION:

Zinc sulphate appears to be an easily administered, safe and well-tolerated alternative for the prevention and treatment of the common cold in children.

Name

Daranee Nasongkhla

Title

Complementary and alternative medicine for prevention and treatment of the common cold (2011)

Link

http://www.cfp.ca/content/57/1/31.long

Abstract

Objective To review the evidence supporting complementary and alternative medicine approaches to treatment and prevention of the common cold in adults.

Quality of Evidence MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched from January 1966 to September 2009 combining the key words common cold or influenza with echinacea, garlic, ginseng, probiotics, vitamin C, and zinc. Clinical trials and prospective studies were included.

Main Message For prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold.

Conclusion Vitamin C can be recommended to Canadian patients for prevention of the common cold. There is moderate evidence supporting the use of Echinacea purpurea and zinc lozenges for treatment. Ginseng and allicin warrant further research.

The common cold is seen frequently by family physicians. It is almost always a viral illness; while rhinoviruses cause 30% to 50% of colds throughout the year and 80% of colds during peak season, up to 200 other viruses have been implicated.1 On average, it affects adults 2 to 4 times per year.2

Symptoms include nasal congestion and discharge, sneezing, cough, sore throat, and fever.3 While benign, they last for several days and cause 40% of all missed work days. Complications include sinusitis, otitis media and pneumonia, exacerbations of asthma and chronic obstructive pulmonary disease, and serious illness in immunocompromised patients. Influenza viruses cause 5% to 15% of acute respiratory infections, resulting in fever, headache, myalgia, and fatigue, and considerable overlap between influenza and the common cold can make accurate diagnosis difficult.3

Few effective treatments exist. Nonsteroidal anti-inflammatory drugs reduce pain symptoms but not the overall duration or severity of a cold,4 and the antiviral drug oseltamivir only reduces symptom duration by 0.55 days in otherwise healthy adults.5 There is no role for antibiotics in the treatment of the common cold. While vaccination of healthy adults prevents influenza, it only reduces incidence of acute respiratory infections by 16%, and work absenteeism by 0.13 days.6

Many patients use complementary and alternative medicine (CAM) therapies to treat the common cold. Canadians spend more than $1 billion per year on CAM therapies,7 but few physicians are familiar with their efficacy or safety. Here we review the evidence for frequently used CAM therapies to help physicians advise patients about the use of such therapies in treating and preventing the common cold.

Name

Ekaterina Balash

Title

Zinc for the treatment of common cold: a systematic review and meta-analysis of randomized controlled trials (2012)

Link

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394849/

Abstract

Background:Results of randomized controlled trials evaluating zinc for the treatment of the common cold are conflicting. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for such use.

Methods:We searched electronic databases and other sources for studies published through to Sept. 30, 2011. We included all randomized controlled trials comparing orally administered zinc with placebo or no treatment. Assessment for study inclusion, data extraction and risk-of-bias analyses were performed in duplicate. We conducted meta-analyses using a random-effects model.

Results:We included 17 trials involving a total of 2121 participants. Compared with patients given placebo, those receiving zinc had a shorter duration of cold symptoms (mean difference −1.65 days, 95% confidence interval [CI] −2.50 to −0.81); however, heterogeneity was high (I2 = 95%). Zinc shortened the duration of cold symptoms in adults (mean difference −2.63, 95% CI −3.69 to −1.58), but no significant effect was seen among children (mean difference −0.26, 95% CI −0.78 to 0.25). Heterogeneity remained high in all subgroup analyses, including by age, dose of ionized zinc and zinc formulation. The occurrence of any adverse event (risk ratio [RR] 1.24, 95% CI 1.05 to 1.46), bad taste (RR 1.65, 95% CI 1.27 to 2.16) and nausea (RR 1.64, 95% CI 1.19 to 2.27) were more common in the zinc group than in the placebo group.

Interpretation:The results of our meta-analysis showed that oral zinc formulations may shorten the duration of symptoms of the common cold. However, large high-quality trials are needed before definitive recommendations for clinical practice can be made. Adverse effects were common and should be the point of future study, because a good safety and tolerance profile is essential when treating this generally mild illness.

The common cold is a frequent respiratory infection experienced 2 to 4 times a year by adults and up to 8 to 10 times a year by children.1–3 Colds can be caused by several viruses, of which rhinoviruses are the most common.4 Despite their benign nature, colds can lead to substantial morbidity, absenteeism and lost productivity.5–7

Zinc, which can inhibit rhinovirus replication and has activity against other respiratory viruses such as respiratory syncytial virus,8 is a potential treatment for the common cold. The exact mechanism of zinc’s activity on viruses remains uncertain. Zinc may also reduce the severity of cold symptoms by acting as an astringent on the trigeminal nerve.9,10

A recent meta-analysis of randomized controlled trials concluded that zinc was effective at reducing the duration and severity of common cold symptoms.11 However, there was considerable heterogeneity reported for the primary outcome (I2 = 93%), and subgroup analyses to explore between-study variations were not performed. The efficacy of zinc therefore remains uncertain, because it is unknown whether the variability among studies was due to methodologic diversity (i.e., risk of bias and therefore uncertainty in zinc’s efficacy) or differences in study populations or interventions (i.e., zinc dose and formulation).

We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for the treatment of the common cold. We sought to improve upon previous systematic reviews11–17 by exploring the heterogeneity with subgroups identified a priori, identifying new trials by instituting a broader search and obtaining additional data from authors.

Name

Mina Mleik

Title

Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold

Link

Cochrane Database of Systematic Reviews  2013, Issue 1. Art. No.: CD000980.

DOI: 10.1002/14651858.CD000980.pub4.

Abstract

Background: Vitamin C (ascorbic acid) for preventing and treating the common cold has been a subject of controversy for 70 years.

Objectives: To find out whether vitamin C reduces the incidence, the duration or severity of the common cold when used either as a continuous regular supplementation every day or as a therapy at the onset of cold symptoms.

Search methods: We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 3, 2012), EMBASE (1990 to November 2012), CINAHL (January 2010 to November 2012), LILACS (January 2010 to November 2012) and Web of Science (January 2010 to November 2012). We also searched the U.S. National Institutes of Health trials register and WHO ICTRP on 29 November 2012.

Selection criteria: We excluded trials which used less than 0.2 g per day of vitamin C and trials without a placebo comparison. We restricted our review to placebo-controlled trials.

Data collection and analysis:

Two review authors independently extracted data. We assessed ’incidence’ of colds during regular supplementation as the proportion of participants experiencing one or more colds during the study period. “Duration” was the mean number of days of illness of cold episodes.

Main results: Twenty-nine trial comparisons involving 11,306 participants contributed to the meta-analysis on the risk ratio (RR) of developing a cold whilst taking vitamin C regularly over the study period. In the general community trials involving 10,708 participants, the pooled RR was 0.97 (95% confidence interval (CI) 0.94 to 1.00). Five trials involving a total of 598 marathon runners, skiers and soldiers on subarctic exercises yielded a pooled RR of 0.48 (95% CI 0.35 to 0.64). Thirty-one comparisons examined the effect of regular vitamin C on common cold duration (9745 episodes). In adults the duration of colds was reduced by 8% (3% to 12%) and in children by 14% (7% to 21%). In children, 1 to 2 g/day vitamin C shortened colds by 18%. The severity of colds was also reduced by regular vitamin C administration. Seven comparisons examined the effect of therapeutic vitamin C (3249 episodes). No consistent effect of vitamin C was seen on the duration or severity of colds in the therapeutic trials. The majority of included trials were randomised, double-blind trials. The exclusion of trials that were either not randomised or not double-blind had no effect on the conclusions.

Member;

Author (Date)

Level of Evidence

Sample/Setting

(# of subjects/ studies, cohort definition etc)

Outcome(s) studied

Key Findings

Limitations and Biases

Fauzia;

Harri Hemilä

(2011)

Systematic Review

-A systematic review of 13 randomized controlled trials

– Number of subjects per trial ranged between lowest of 48 to highest of 247

– Therefore a total of 1,402 subjects were considered in this systematic review

– 5 trials supplied low Zn dose (<75 mg/day) and 8 supplied high Zn dose (>75 mg/day).

-Average duration of colds (days) of Zn/Placebo

-Trials with Zn doses >75 mg/day had significant reduction in the duration of colds.

– The 5 trials that supplied Zn doses <75 mg/day did not have a significant effect on cold duration.

-Results- 95% CI of 42% reduction in duration of a cold  for three high dose zinc acetate trials.

-5 non-zinc acetate trials – 95% CI:12%-28% reduction in colds

-8 high dose trials- 95% CI: 27%-37% reduction in colds

– Some divergent results because of the variation between trials  in total daily dose of Zn lozenges.

– Composition of lozenges and level of free Zn ions  varied among the studies. 3/8 of  high dose studies were composed of Zn acetate and the other 3 were non-Zn acetate.

Lauren;

Zafer Kurugol, 2005

Randomised Controlled Trial (Level 1b)

200 Participants; ages 2-10 y

Placebo group (n=100; M/F =51/49)

Zinc group (n=100; M/F=48/52)

Randomized, double blind, placebo-

controlled, prospective study

Primary outcome – # of colds per study child

Secondary Outcome – duration and severity of cold symptoms

7 month trial

Prophylactic administration of zinc sulphate significantly decreases the occurrence of common cold in children.

Zinc sulphate shortens the mean duration of colds and reduces the severity of symptoms.

1. Zinc group duration = 95% CI 4.6-4.9d severity of symptoms based on 1-10 scale = 6.8 +/- 1.8 (p=0.114)
2. Placebo group duration = 95% CI 5.1-5.4d severity of symptoms = 6.7 +/- 1.9

Trial was conducted in Turkey.  Country may be exposed to different strains of cold viruses not general in the US.

Severity of symptoms was based on a 1-10 scale (10 being the worst).  Individual perception of pain cannot be standardized.

Study on children. Are the effects comparable to the adult population?

Daranee: Nahas, Balla (2011)

Systematic Review

Meta-analyses and

Randomized Control Trials of adults and children.

Vitamin C- 38 trials considered for treatments or prevention

Zinc- 30 trials considered for treatment and prevention

Incidences of common cold, cold duration and severity

-30 reviews regarding use of Vitamin C:

Number of incidence of Cold: OR 0.96 (95% CI 0.92 -1.0)

Decrease in duration of days of symptoms: 8% decrease in adults, 18% decrease in children (95% CI between 7% to 30%) (A decrease in duration represents a decrease of 1.5-2 days of symptom, which assumes the average cold lasts 7 to 10 days. This is considered a clinically relevant decrease of duration)

-5 studies regarding use of Zinc lozenges:

Reduction in days of symptoms and symptom severity: 1.3 – 6.9 day reduction (No CI stated)

-8 RCT regarding use of Zinc lozenges:

Decrease in number of days of symptoms after 7 days: OR 0.52, 95% CI 0.25 to 1.2

As a Canadian review it focused on Canadian studies. Some of the studies used are based in geographic location that may not have analogous seasonal weather as our target population in New York. Some of the Canadian studies focus on Sub arctic conditions that may influence the incidence, severity or duration of the common cold.

Balash:

Michelle Science (2012)

Systematic Review, Meta-

analysis

RCTs of 17 trials, 2121 participants, age 1-65.

Primary-duration of cold systems.Secondary-the severity of symptoms, the presence of symptoms after three and seven days, and adverse effects.

In comparing with placebo, Zinc shortened the duration of cold symptoms (mean difference -1.65 days, 95% CI) i adults, but not significant effect in children (mean difference -0.26, 95% CI)

1. Large heterogeneity of participants

2. All evaluated studies were industry funded

3. Ineffective blinding related to taste of placebo

4. Selection bias -authors excluded some articles that did not satisfy their hypothesis ( trials where cold was experimentally  induced- they found no effect in using using Zinc)

Mina, Hemilä H, Chalker E (2013)

Meta-

analysis

Randomised, double-blind trials, placebo controlled trials.
29 trials involving total 11,306 participants (including children and adults of either gender)
-general community trials involving 10,708 participants
-Five trials involving a total of 598 marathon runners, skiers and soldiers on
subarctic exercises
-oral sup of Vit C daily or for a period =>0.2 g

-there were regular and therapeutic sup.

Primary outcomes: incidence and duration

Secondary outcomes: severity and possible side effects

-RR was 0.97 (95% confidence interval (CI) 0.94 to 1.00) for general community
-RR of 0.48 (95% CI 0.35 to 0.64) for restricted subpopulation
-common cold duration (9745 episodes). In adults the duration
of colds was reduced by 8% (3% to 12%) and in children by 14% (7% to 21%). In children, 1 to 2 g/day vitamin C shortened colds
by 18%. The severity of colds was also reduced by regular vitamin C administration.
-therapeutic vitamin C (3249 episodes). No consistent effect of vitamin C was seen on the duration or severity of colds in the therapeutic trials.

-the reviewers had prior knowledge of the literature

on vitamin C and the common cold, and specific knowledge of the papers under consideration

 -Their results relate to low doses

–variation in methodology and the substantial heterogeneity in results from this large number of trial results