Zinc for the common cold

Journal reference: Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No.: CD001364 ^[1]

Link: http://dx.doi.org/10.1002/14651858.CD001364.pub3

Published: 16 February 2011

Evidence cookie says...

Zinc administered within 24 hours of the symptoms of a common cold is associated with favourable outcomes but with some side-effects.  ↓ cold symptom duration by ~ 1 day ↓ cold symptom severity (minimal) ↑ side-effects: bad taste (NNH = 7) and nausea (NNH = 12) It is premature to routinely recommend zinc therapy for the common cold. It is reasonable to direct patients seeking community remedies towards zinc rather than other common treatments (echinacea, vitamin C). Note: there are limitations to the evidence. See below for more details.

Article details:

Study design:

systematic review of randomised controlled trials

Study aim:

to assess the effect of zinc on common cold symptoms

Study conclusion:

Zinc administered within 24 hours of onset of symptoms reduces the duration and severity of the common cold in health people. When supplemented for at least five months, it reduces cold incidence, school absenteeism and prescription of antibiotics in children. There is potential for zinc lozenges to produce side effects. In view of this and the differences in study populations, dosages, formulations and duration of treatment, it is difficult to make firm recommendations about the dose, formulation and duration that should be used ^[1].

Critical appraisal:

Are the trial results valid?

Internal validity: Wikipedia

Is it unlikely that important, relevant studies were missed?

Yes.

Extensive and detailed electronic searches performed. This systematic review builds on older versions of the same review with evidence from newer studies.

Were the criteria used to select articles for inclusion appropriate?

Yes.

• double-blind, placebo-controlled randomised controlled trials
• all participants in such trials
• therapeutic trials:
  • intervention commenced within three days of participants developing common cold symptoms
  • 1.5 to 2 hourly treatments with a zinc or placebo lozenge during waking hours (more than 6 hours a day)
  • at least 5 or more consecutive days
• prophylactic trials:
  • commenced and continued throughout cold season for at least five months
  • all zinc formulations considered

Were the included studies sufficiently valid for the type of question asked?

Yes.

• the review authors systematically and rigorously assessed the included studies for their methodological quality
• the majority were at low risk of bias on all items (adequate sequence generation? allocation concealment? blinding? incomplete outcome data addressed? free from selective reporting? free of other bias?)
• some studies were considered at high risk of bias on a few items

Were the results similar from study to study?

No / depended on outcome measure.

• there was large heterogeneity between the included trials
• this means that there is substantial uncertainty to the reliability of the pooled result
• I² statistic (the proportion that the differences in results are due to differences between the studies) for outcome measures:
  • duration of cold symptoms: 93%
  • severity of cold symptoms: 75%
  • incidence of common cold: 88%
  • any adverse event: 51%

What were the results?

Primary outcome

Duration of cold symptoms (zinc intervention administered within 24 hours of cold symptoms):

• placebo: mean duration of cold symptoms, 5.1 to 8.5 days
• zinc: standardised mean difference: –0.97 days (95% CI -1.56 to -0.38)
• interpretation: favourable result for zinc; on average the duration of symptoms was one day less, though the true value may conceivably lie anywhere from about 9 hours to 37 hours)

Severity of cold symptoms (score):

• placebo: mean severity of symptom score ranged from 0.4 to 5.61
• zinc: standardised mean difference: -0.39 (95% CI -0.77 to -0.02)
• interpretation: favourable results for zinc; though the heterogeneity (large range of mean symptom scores in the included studies) and very wide confidence intervals are problematic; nevertheless, the conceivable range of symptom improvement in the confidence interval ranges from no improvement to mild improvement
• note on symptom scoring:
  • 0 = no symptoms
  • 1 = mild symptoms
  • 2 = moderate symptoms
  • 3 = severe symptoms

Incidence of common cold (zinc treatment for over cold season for at least 5 months):

• placebo: 618 per 1000 person-time
• zinc: 382 per 1000 person-time (95% CI 354 to 431)
  • risk ratio (RR) = 0.64 (95% CI 0.47 – 0.88)
  • number needed to treat (NNT) = 4.2 (95% CI 3.8 – 5.3)
  • note: NNT calculated by Morsels of Evidence
  • interpretation: zinc therapy significantly decreased the incidence of the common cold

Other outcomes:

Any adverse events:

• placebo: 481 per 1000 person-time
• zinc: 562 per 1000 person-time (95% CI 252 to 898)
  • odds ratio (OR) = 1.59 (95% CI 0.97 – 2.58)
  • number needed to harm (NNH) = 12.3 (95% CI 2.4 to infinity)
  • note: NNH calculated by Morsels of Evidence
  • interpretation: zinc therapy was associated with more adverse events but the confidence interval was wide and the result was not statistically significant.  Nevertheless, it is likely that there is a real effect that is clinically significant but there is substantial uncertainty to the true value

Specific side-effects:

• bad taste:
  • suffered by 33.0% of the intervention group vs 18.6% of the placebo group
  • OR = 2.64 (CI 1.91 – 3.64)
  • NNH = 6.9 (CI 5.0 – 9.6)
• nausea:
  • suffered by 17.1% of the intervention group vs 8.9% of the placebo group
  • OR = 2.15 (CI 1.44 – 3.23)
  • NNH = 12.2 (CI 8.2 – 18.3)

Will the results help me care for my patient?

External validity: Wikipedia

Are the participants different to my patient?

• mixed group of adults and children
• subgroup analyses not possible due to limited number of participants
• no studies from low or middle income countries
• no studies in participants who may have a worse outcome with the common cold (chronic disease, immunodeficiency, asthma, etc.)

Is the treatment feasible?

Unclear.

• the therapy used in the zinc treatment group is possibly unrealistic in the primary health care setting (1.5 to 2 hourly zinc lozenges for at least 6 hours a day, for at least 5 days)
• the therapy used in the zinc prevention group is arguably infeasible in the primary health care setting (daily medication for almost half the year in otherwise healthy individuals to prevent an otherwise mild self-limiting infection)

Were all the clinically important outcomes considered?

• this study provided moderate level evidence for duration of cold symptoms, severity of cold symptoms, incidence of the common cold and adverse events
• a number of other important outcome measures were assessed but the level of evidence is low

Are the treatment benefits worth the potential harms/costs?

Unclear.

• zinc does appear to be associated with a clinically significant effect on the duration of a cold, reducing its length by on average a day
• even if the least favourable end of the confidence interval is true, it is still associated with a reduction of duration of approximately 9 hours, which is arguably meaningful
• zinc is associated with a statistically significant reduction in the severity of a cold, but the result is of questionable clinical significance
• zinc is associated with more side-effects with approximately 1 extra patient harmed for every 12 on zinc

Study weaknesses (summary)

• the weaknesses mostly relate to the limitations of the included studies:
  • substantial variations in study populations, the dosage, formulation of zinc, treatment duration
  • substantial heterogeneity between the results
• difficult to make any firm recommendations when applying the results to clinical populations

Study strengths (summary)

• rigorous systematic review
• detailed assessment of methodological quality of included trials

Biases and conflicts of interests

• nil declared and none seem obvious

Clinical relevance to primary health care

The common cold is one of the most common presentations to Australian general practice. Upper respiratory tract infections, the majority of which are colds, is the third most frequent problem managed; 5.8 cases per every 100 patient encounters ^[2]. There are no proven treatments for the common cold.

This well conducted systematic review demonstrates that zinc therapy is associated with favourable effects on the common cold.  Zinc therapy is associated with:

• reduced duration of cold symptoms
• reduced severity of symptoms
• reduced incidence of cold if used regularly throughout cold season

Zinc, however is associated with more side-effects. The reduction in cold symptom severity appears to be of minimal clinical significance. Moreover, it is questionable whether the intensity and frequency of the dosing schedule is realistic for patients suffering the cold in the primary health care setting. The substantial variability in study populations, dosage, formulation, treatment duration; and the large heterogeneity preclude any firm recommendation on who, when, and how to treat.

It is premature for Australian general practitioners to routinely recommend or prescribe zinc therapy for the treatment of the common cold for all patients. However, patients interested in trying over-the-counter remedies could be directed towards zinc, rather than other commonly used cold treatments with limited or inconsistent evidence (e.g., echinacea and vitamin C). Theses patients should be made aware of the dosing schedule used in the included studies (every 1.5 to 2 hourly, for at least 6 hours, for 5 days).

References

1. Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No.: CD001364
2. Britt H, Miller GC, Charles J, et al. General practice activity in Australia 2006-07. Australian General Practice Statistics and Classification Centre, Australian Institute of Health and Welfare. 30 January 2008