Honey for acute cough in children

Olabisi Oduwole; Ekong E Udoh; Angela Oyo‐Ita; Martin M Meremikwu

doi:10.1002/14651858.CD007094.pub5

. 2018 Apr 10;2018(4):CD007094. doi: 10.1002/14651858.CD007094.pub5

Honey for acute cough in children

Olabisi Oduwole ^1,^✉, Ekong E Udoh ², Angela Oyo‐Ita ³, Martin M Meremikwu ²

Editor: Cochrane Acute Respiratory Infections Group

PMCID: PMC6513626 PMID: 29633783

Abstract

Background

Cough causes concern for parents and is a major cause of outpatient visits. Cough can impact quality of life, cause anxiety, and affect sleep in children and their parents. Honey has been used to alleviate cough symptoms. This is an update of reviews previously published in 2014, 2012, and 2010.

Objectives

To evaluate the effectiveness of honey for acute cough in children in ambulatory settings.

Search methods

We searched CENTRAL (2018, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (2014 to 8 February 2018), Embase (2014 to 8 February 2018), CINAHL (2014 to 8 February 2018), EBSCO (2014 to 8 February 2018), Web of Science (2014 to 8 February 2018), and LILACS (2014 to 8 February 2018). We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) on 12 February 2018. The 2014 review included searches of AMED and CAB Abstracts, but these were not searched for this update due to lack of institutional access.

Selection criteria

Randomised controlled trials comparing honey alone, or in combination with antibiotics, versus no treatment, placebo, honey‐based cough syrup, or other over‐the‐counter cough medications for children aged 12 months to 18 years for acute cough in ambulatory settings.

Data collection and analysis

We used standard methodological procedures expected by Cochrane.

Main results

We included six randomised controlled trials involving 899 children; we added three studies (331 children) in this update.

We assessed two studies as at high risk of performance and detection bias; three studies as at unclear risk of attrition bias; and three studies as at unclear risk of other bias.

Studies compared honey with dextromethorphan, diphenhydramine, salbutamol, bromelin (an enzyme from the Bromeliaceae (pineapple) family), no treatment, and placebo. Five studies used 7‐point Likert scales to measure symptomatic relief of cough; one used an unclear 5‐point scale. In all studies, low score indicated better cough symptom relief.

Using a 7‐point Likert scale, honey probably reduces cough frequency better than no treatment or placebo (no treatment: mean difference (MD) ‐1.05, 95% confidence interval (CI) ‐1.48 to ‐0.62; I² = 0%; 2 studies; 154 children; moderate‐certainty evidence; placebo: MD ‐1.62, 95% CI ‐3.02 to ‐0.22; I² = 0%; 2 studies; 402 children; moderate‐certainty evidence). Honey may have a similar effect as dextromethorphan in reducing cough frequency (MD ‐0.07, 95% CI ‐1.07 to 0.94; I² = 87%; 2 studies; 149 children; low‐certainty evidence). Honey may be better than diphenhydramine in reducing cough frequency (MD ‐0.57, 95% CI ‐0.90 to ‐0.24; 1 study; 80 children; low‐certainty evidence).

Giving honey for up to three days is probably more effective in relieving cough symptoms compared with placebo or salbutamol. Beyond three days honey probably had no advantage over salbutamol or placebo in reducing cough severity, bothersome cough, and impact of cough on sleep for parents and children (moderate‐certainty evidence). With a 5‐point cough scale, there was probably little or no difference between the effects of honey and bromelin mixed with honey in reducing cough frequency and severity.

Adverse events included nervousness, insomnia, and hyperactivity, experienced by seven children (9.3%) treated with honey and two children (2.7%) treated with dextromethorphan (risk ratio (RR) 2.94, 95% Cl 0.74 to 11.71; I² = 0%; 2 studies; 149 children; low‐certainty evidence). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14, 95% Cl 0.01 to 2.68; 1 study; 80 children; low‐certainty evidence). When honey was compared with placebo, 34 children (12%) in the honey group and 13 (11%) in the placebo group complained of gastrointestinal symptoms (RR 1.91, 95% CI 1.12 to 3.24; I² = 0%; 2 studies; 402 children; moderate‐certainty evidence). Four children who received salbutamol had rashes compared to one child in the honey group (RR 0.19, 95% CI 0.02 to 1.63; 1 study; 100 children; moderate‐certainty evidence). No adverse events were reported in the no‐treatment group.

Authors' conclusions

Honey probably relieves cough symptoms to a greater extent than no treatment, diphenhydramine, and placebo, but may make little or no difference compared to dextromethorphan. Honey probably reduces cough duration better than placebo and salbutamol. There was no strong evidence for or against using honey. Most of the children received treatment for one night, which is a limitation to the results of this review. There was no difference in occurrence of adverse events between the honey and control arms.

Plain language summary

Honey for acute cough in children

Review question

Can honey reduce cough symptoms caused by bacteria and viruses in children?

Background

Cough causes concern for parents and is a major reason for outpatient visits. Honey is believed to prevent growth of germs and reduce inflammation.

Search date

We searched databases to 8 February 2018 and trial registers to 12 February 2018.

Study characteristics

We included six small trials involving 899 children aged 12 months to 18 years conducted in Iran, Israel, the USA, Brazil, and Kenya. This update included three new trials conducted between 2007 and 2016 that involved 331 children.

Study funding sources

Two studies were supported by pharmaceutical manufacturers; one by a university research centre; one by the Honey Board of Israel and non‐government agencies; and one by USA National Honey Board. One study did not report funding sources.

Key results

We compared honey to over‐the‐counter cough preparations, bromelin (a pineapple enzyme) mixed with honey, fake treatment (placebo), and no treatment.

Honey probably reduces cough symptoms more than placebo and salbutamol (a drug that opens lung airways) when given for up to three days. Honey is probably more effective at providing cough relief and reducing the impact of cough on children's sleep at night than no treatment.

There may be little or no difference between the effects of honey and dextromethorphan (an ingredient in over‐the‐counter cough remedies) or honey and bromelin with honey on all cough symptoms. Honey may be better than diphenhydramine (an antihistamine) at relieving and reducing children's cough.

The parents of seven children given honey and two given dextromethorphan reported side effects in their children, such as not falling asleep easily, restlessness, and becoming overexcited. The parents of three children in the diphenhydramine group reported that their children were often sleepy. The parents of nine children given salbutamol, seven given honey, and six given placebo reported diarrhoea. The parents of four children who received salbutamol and one child given honey reported rash.

We found no evidence for or against the use of honey to relieve cough in children. Using honey for infants aged up to 12 months is not advised because of poor immunity against bacteria that may be present, which can cause paralysis. Most of the children received honey for just one night, which is a limitation to the results of this review.

Quality of the evidence

Overall, evidence quality was low to moderate. Some studies did not blind participants.

Summary of findings

Background

Description of the condition

Cough is a normal protective mechanism (Landau 2006), and a means by which the respiratory system rids itself of excessive secretions and foreign bodies (Cuestas 2017). Cough can be caused by bacterial or viral infections, the presence of an irritant or allergen in the respiratory tract, or both (Ma 2017). Respiratory infections can be situated along the upper or lower respiratory tract, and the resulting cough can be either productive or unproductive of sputum. Unproductive cough is usually referred to as 'dry' cough. Children with dry cough tend to have minimal airway secretions (Chang 2005).

Cough can be classified as acute or chronic. Chronic cough lasts for more than three weeks (Smith 2016). Acute cough from upper respiratory tract infection (URTI) is a very common symptom seen in primary care settings or by general practitioners (Butler 2005; Derebery 2013). Most coughs from URTIs are caused by viral infections (Braman 2006; Butler 2005). Cough is cause for parental concern (Hay 2003), and a major reason for outpatient visits for both children and adults (Kigen 2015; Kusel 2007). Cough can impact on quality of life (French 2002), cause anxiety, and affect the sleep of children and their parents. For these reasons, immediate remedy for cough is often sought by parents and carers of children with cough.

Description of the intervention

Many people use over‐the‐counter (OTC) cough medications, and general practitioners in primary care settings often recommend these as first‐line treatments (Kigen 2015). Although many OTC cough preparations are available, there is no good evidence regarding their efficacy (Chang 2014; Smith 2014). In children, OTC cough medications may be associated with serious adverse events such as death, altered consciousness, and arrhythmias (CDC 2007; Gunn 2001; Kelly 2004). Study findings vary in reported relief of cough symptoms, with several studies finding no effect compared with placebo (Banderali 1995; Freestone 1997; Kurth 1978; Smith 2014).

Cough mixtures contain a variety of drugs with differing modes of action, which makes them difficult to compare (Morice 1998). Over‐the‐counter cough medications may contain dextromethorphan hydrobromide, phenylephrine hydrochloride, chlorpheniramine maleate, and methylparaben (El‐Gindy 2005).

Honey is a sweet, viscous liquid with a complex chemical composition of approximately 25 carbohydrates (Sanz 2004), free amino acids (Hermosin 2003; Suárez‐Luque 2002), vitamins and trace elements (Golob 2005; Hernández 2005; Nanda 2003; Tuzen 2007; Yao 2003). Honey also contains compounds that function as antioxidants such as flavonoids and carotenoids, polyphenol, phenolic acids, vitamin C, and glucose oxydase enzymes (Khalil 2010; Nagai 2006).

How the intervention might work

Honey confers antibacterial (Lusby 2005; Mullai 2007), antiviral (Shahzad 2012; Watanabe 2014; Zeina 1996), antifungal (Ahmed 2013b; Irish 2006; Kuncic 2012), and anti‐inflammatory properties (Tonks 2003). Studies of the antimicrobial effect of honey show that it has broad‐spectrum antimicrobial effects on various gram‐negative and gram‐positive bacteria (Agbaje 2006; Katrina 2014). Honey is reported to be active against certain bacteria that have been isolated from the upper respiratory tract such as Staphylococcus aureus, Enterococcus faecalis,Candida albicans,Klebsiella pneumoniae,Pseudomonas aeruginosa,Escherichia coli, Salmonella spp., and Shigella dysenteriae (Adeleye 2003; Kousalya 2010; Mullai 2007). Honey has antiviral effects against Varicella zoster virus (Shahzad 2012), influenza virus (Watanabe 2014), and rubella virus (Zeina 1996). It is believed that the antibacterial activities of honey are intrinsic and not dependent on any external factors such as geographical location or its source (Katrina 2014).

Honey has been used in traditional medicine to treat cough (Adeleye 2003), and in modern medicine to treat infected wounds (Lusby 2005; Molan 2006); it is also an ingredient in some cough syrups (Zeina 1996). However, the use of honey in infants aged under 12 months is restricted because of babies' poor immunity against Clostridium botulinum, a possible contaminant in honey (Küplülü 2006; Nevas 2002).

Why it is important to do this review

Identification of ineffective preparations for cough could reduce costs for consumers and healthcare providers (Smith 2014). Cochrane Reviews have assessed the effectiveness of OTC cough medications (Chang 2014; Smith 2014), but none have studied honey for cough relief.

If effective, honey may save significant annual expenditure on OTC cough medications (Dicpinigaitis 2011). Previous versions of this review were inconclusive about the effectiveness of using honey to treat acute cough in children (Oduwole 2010; Oduwole 2012; Oduwole 2014a). The aim of this review was to examine the comparative effectiveness of honey to relieve acute cough in children.

Objectives

To evaluate the effectiveness of honey for acute cough in children in ambulatory settings.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs).

Types of participants

We included children aged 12 months to 18 years with cough caused by acute viral or bacterial URTI. We excluded studies that included participants with chronic cough (lasting for more than three weeks). We also excluded studies with sample sizes of fewer than 10 per intervention.

Types of interventions

Studies that compared:

honey only versus:
1. honey‐based cough syrup;
2. non‐honey cough syrup;
3. placebo; and
4. no treatment;
honey plus antibiotics versus antibiotics alone; and
honey plus antibiotics versus non‐honey cough syrups plus antibiotics

were eligible for inclusion.

Types of outcome measures

Primary outcomes

Duration of cough.
Symptomatic relief of cough (frequency of cough, reduction in severity, and less bothersome cough).

Secondary outcomes

Improvement in quality of sleep at night for children (cough impact on sleep score).
Improvement in quality of sleep at night for caregiver (cough impact on sleep score).
Improvement in quality of life (e.g. school attendance and playing).
Adverse effects.
Improvement in appetite.
Cost of honey alone compared with other cough syrups.

Search methods for identification of studies

Electronic searches

For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), part of the Cochrane Library (searched 8 February 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (Ovid) (October 2014 to 8 February 2018), Embase (Elsevier) (October 2014 to 8 February 2018), CINAHL (Cumulative Index to Nursing and Allied Health Literature) (EBSCO) (October 2014 to 8 February 2018), Web of Science (Clarivate Analytics) (October 2014 to 8 February 2018), and LILACS (Latin American and Caribbean Health Sciences Literature) (BIREME) (October 2014 to 8 February 2018). The 2014 version of this review included searches of AMED (Appendix 1) and CAB Abstracts (Appendix 2), but these were not searched for this update due to lack of institutional access to those databases. Details of previous searches are in Appendix 3.

We used the search strategy in Appendix 4 to search MEDLINE and CENTRAL, and modified terms to search Embase (Appendix 5), CINAHL (Appendix 6), Web of Science (Appendix 7), and LILACS (Appendix 8). We did not combine the MEDLINE search string with the Cochrane Highly Sensitive Search Strategies for identifying randomised trials in MEDLINE (Lefebvre 2011), because we found very few results. We imposed no language or publication restrictions.

Searching other resources

We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (apps.who.int/trialsearch/) and ClinicalTrials.gov (www.clinicaltrials.gov) on 12 February 2018. We checked the reference lists of all relevant articles obtained from our search and those from previously published systematic reviews to identify additional articles. We also contacted the authors of studies added for this update for information and unpublished data (Ahmadi 2013; Paul 2007; Waris 2014).

Data collection and analysis

Selection of studies

Two review authors (OO, EU) independently screened search results using Covidence for eligible studies based on a priori inclusion criteria (Covidence). Any disagreements were resolved by consensus.

Data extraction and management

One review author (OO) independently extracted and entered data into Review Manager 5 (Review Manager 2014). Ahmadi 2013 was translated from Farsi to English for assessment. Another review author (EU) checked data extraction for accuracy and completeness. Any disagreements were resolved by consensus.

Assessment of risk of bias in included studies

Two review authors (OO, EU) assessed risk of bias of the included trials using Cochrane's 'Risk of bias' tool. We assessed random sequence generation, allocation concealment, blinding, selective reporting, and other sources of bias, and recorded the assessment in the 'Risk of bias' tables. We ranked the studies as low, unclear, or high risk of bias, as recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Measures of treatment effect

We used one‐way analysis of variance (ANOVA) to compare treatment effects for cough duration, cough symptoms, and quality of sleep. We presented estimates of effects as mean differences (MD) derived from parents' subjective assessment of cough symptoms and cough impact on sleep quality using validated questions on a 7‐point Likert scale (Likert 1932).

We used the mean and standard deviation (SD) to analyse pair‐wise comparisons of treatment effect between honey and placebo and honey and salbutamol on cough duration. We also analysed pair‐wise comparisons of other outcomes using generic inverse variance in Review Manager 5 (Review Manager 2014). We estimated MD between children's Likert scores at baseline and postintervention for frequency of cough, bothersome cough, and cough impact on quality of sleep for child and parent. We used the MD and standard error (SE) for the pair‐wise comparison of treatment effect between honey and dextromethorphan, honey and diphenhydramine, honey and no treatment, honey and placebo, honey and salbutamol, and honey and bromelin. We used the Mantel‐Haenszel method to analyse the risk ratio (RR) for adverse events in Review Manager 5 (Review Manager 2014). We presented results for other measures of effects not presented as MD in Table 6.

1. Pre‐ and postintervention comparison of honey on cough frequency and severity expressed as medians.

Study ID	Cough	Honey (N = 29)	Bromelin   (pineapple extract) + honey (N = 31)	P value	Certainty of the evidence
Peixoto 2016	Frequency of cough¹
	Before, median (P25 to P75) After, median (P25 to P75) Mean ± SD	3 (2 to 4) 1 (1 to 1) 1.76 ± 0.87	3 (2 to 3) 1 (1 to 1) 1.71 ± 0.78	0.83² 0.94³	⊕⊕⊕⊝  MODERATE ⁴
	Severity of cough¹
	Mean ± SD assessed with: unvalidated 5‐point cough scale from 0 to 4	‐0.86 ± 0.45	‐0.97 ± 0.62	0.32² 0.22³	⊕⊕⊕⊝  MODERATE ⁴
		Honey (N = 63)	Diphenhydramine (N = 63)
Ahmadi 2013	Proportion of children with reduction in frequency and severity of daytime cough⁵	84.1% (N = 53)	58.7% (N = 37)	"< 0.02"	⊕⊕⊕⊝  MODERATE ⁴
Ahmadi 2013	Proportion of children with reduction in frequency and severity of nighttime cough⁵	79.4% (N = 50)	58.7% (N = 37)	"< 0.02"	⊕⊕⊕⊝  MODERATE ⁴

Honey compared to dextromethorphan for acute cough in children
Patient or population: acute cough in children  Setting: ambulatory  Intervention: honey  Comparison: dextromethorphan
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Outcomes	Risk with dextromethorphan	Risk with honey	Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Duration of cough	‐	‐	‐	‐	‐	Not assessed
Frequency of cough¹	The mean frequency of cough (reduction in frequency of cough score) was ‐1.54.	MD 0.07 score lower  (1.07 lower to 0.94 higher)	‐	149  (2 RCTs)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 1 day
Severity of cough¹	The mean severity of cough (reduction in severity of cough score) was ‐1.52.	MD 0.13 score lower  (1.25 lower to 0.99 higher)	‐	149  (2 RCTs)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 1 day
Bothersome cough¹	The mean bothersome cough (reduction in bothersome nature of cough score) was ‐1.94.	MD 0.29 score higher  (0.56 lower to 1.14 higher)	‐	69  (1 RCT)	⊕⊕⊕⊝  MODERATE ⁵	Follow‐up: mean 1 day
Cough impact on children's sleep¹	The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.75.	MD 0.03 score higher  (1.12 lower to 1.19 higher)	‐	149  (2 RCTs)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 6 days
Cough impact on parents' sleep¹	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.97.	MD 0.16 score lower  (0.84 lower to 0.53 higher)	‐	149  (2 RCTs)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 1 day
Adverse events	Population
Nervousness, insomnia, hyperactivity	3 per 100	8 per 100 (2 to 32)	RR 2.94  (0.74 to 11.71)	149  (2 RCTs)	⊕⊕⊝⊝  LOW ⁴	Follow‐up: mean 1 day
Stomachache, nausea, and vomiting	1 per 100	7 per 100 (0 to 100)	RR 4.86  (0.24 to 97.69)	69  (1 RCT)	⊕⊕⊝⊝  LOW ⁵
Drowsiness	1 per 100	4 per 100  (0 to 100)	RR 2.92  (0.12 to 69.20)	69  (1 RCT)	⊕⊕⊝⊝  LOW ⁵
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence  High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Honey compared to diphenhydramine for acute cough in children
Patient or population: acute cough in children  Setting: ambulatory  Intervention: honey  Comparison: diphenhydramine
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Outcomes	Risk with diphenhydramine	Risk with honey	Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Cough duration	‐	‐	‐	‐	‐	Not assessed
Frequency of cough¹	The mean frequency of cough (reduction in cough frequency score) was ‐1.73.	MD 0.57 lower  (0.9 lower to 0.24 lower)	‐	80  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 1 day
Severity of cough¹	The mean severity of cough (reduction in cough severity score) was ‐1.83.	MD 0.6 lower  (0.94 lower to 0.26 lower)	‐	80  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 1 day
Cough impact on children's sleep¹	The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.64.	MD 0.55 score lower  (0.87 lower to 0.23 lower)	‐	80  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 6 days
Cough impact on parents' sleep¹	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.89.	MD 0.48 lower  (0.76 lower to 0.2 lower)	‐	80  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 1 day
Adverse event: Somnolence	Population	1 per 100  (0 to 20)	RR 0.14  (0.01 to 2.68)	80  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 1 day
Adverse event: Somnolence	8 per 100	1 per 100  (0 to 20)	RR 0.14  (0.01 to 2.68)	80  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 3}	Follow‐up: mean 1 day
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence  High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Honey compared to no treatment for acute cough in children
Patient or population: acute cough in children  Setting: ambulatory  Intervention: honey  Comparison: 'no treatment'
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Outcomes	Risk with no treatment	Risk with honey	Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Cough duration	‐	‐	‐	‐	‐	Not assessed
Frequency of cough¹	The mean frequency of cough (reduction in cough frequency score) was ‐0.98.	MD 1.05 lower  (1.48 lower to 0.62 lower)	‐	154  (2 RCTs)	⊕⊕⊕⊝  MODERATE ^{2, 3}	Follow‐up: mean 1 day
Severity of cough¹ assessed with: 7‐point Likert scale  Scale from 0 to 6	The mean severity of cough (reduction in severity of cough score) was ‐1.13.	MD 1.03 score lower  (1.59 lower to 0.47 lower)	‐	154  (2 RCTs)	⊕⊕⊕⊝  MODERATE ^{2, 3}	Follow‐up: mean 1 day
Bothersome cough¹  assessed with: 7‐point Likert scale  Scale from 0 to 6	The mean bothersome cough (reduction in bothersome nature of cough score) was ‐1.30.	MD 0.93 score lower  (1.98 lower to 0.12 higher)	‐	74  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 4}	Follow‐up: mean 1 day
Cough impact on children's sleep¹  assessed with: 7‐point Likert scale  Scale from 0 to 6	The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.28.	MD 1.04 score lower  (1.57 lower to 0.51 lower)	‐	154  (2 RCTs)	⊕⊕⊕⊝  MODERATE ^{2, 3}	Follow‐up: mean 6 days
Cough impact on parents' sleep¹ assessed with: 7‐point Likert scale  Scale from 0 to 6	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.46.	MD 0.88 score lower  (1.23 lower to 0.52 lower)	‐	154  (2 RCTs)	⊕⊕⊕⊝  MODERATE ^{2, 3}	Follow‐up: mean 1 day
Adverse events	Population
Nervousness, insomnia, hyperactivity	1 per 100	6 per 100  (1 to 33)	RR 9.40 (1.16 to 76.20)	154  (2 RCTs)	⊕⊕⊝⊝  LOW ^{2, 4}	Follow‐up: mean 1 day
Stomachache, nausea, and vomiting	1 per 100	7 per 100  (0 to 62)	RR 5.90 (0.27 to 127.14)	74  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 4}
Drowsiness	1 per 100	4 per 100  (0 to 53)	RR 3.43 (0.14 to 87.09)	74  (1 RCT)	⊕⊕⊝⊝  LOW ^{2, 4}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence  High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Honey compared to placebo for acute cough in children
Patient or population: acute cough in children  Setting: ambulatory  Intervention: honey  Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Outcomes	Risk with placebo	Risk with honey	Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Day 1
Frequency of cough¹	The mean frequency of cough (reduction in cough frequency score) was ‐0.99.	MD 1.62 score lower  (3.02 lower to 0.22 lower)	‐	402  (2 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 1 day
Severity of cough¹	The mean severity of cough (reduction in severity of cough score) was ‐0.80.	MD 1.07 score lower  (2.43 lower to 0.3 higher)	‐	402  (2 RCT)	⊕⊕⊕⊝  MODERATE ²
Bothersome cough (mean improvement score)¹	The mean bothersome cough (reduction in bothersome nature of cough) was ‐1.08.	MD 1.4 score lower  (2.82 lower to 0.03 higher)	‐	402  (2 RCTs)	⊕⊕⊕⊝  MODERATE ²
Cough impact on children's sleep¹	The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.03.	MD 1.21 score lower  (2.61 lower to 0.19 higher)	‐	402  (2 RCTs)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 6 days
Cough impact on parents' sleep¹	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.44.	MD 1.29 score lower  (2.71 lower to 0.13 higher)	‐	402  (2 RCTs)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 1 day
Day 3
Frequency of cough¹	The mean frequency of cough (reduction in frequency of cough score) was ‐0.9.	MD 1.13 score lower  (1.71 lower to 0.55 lower)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 6 days
Severity of cough¹	The mean severity of cough (reduction in severity of cough score) was ‐1.08.	MD 0.85 score lower  (1.41 lower to 0.29 lower)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Bothersome cough¹	The mean bothersome cough (reduction in bothersome nature of cough score) was ‐0.99.	MD 1.33 score lower  (1.87 lower to 0.79 lower)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on children's sleep¹	The mean cough impact on children's sleep (cough impact on children's sleep score) was ‐0.46.	MD 0.93 score lower  (1.42 lower to 0.44 lower)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on parents' sleep³	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.04.	MD 0.88 score lower  (1.38 lower to 0.38 lower)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Day 5
Cough duration	The mean cough duration was 5.18 days.	MD 0.72 days lower  (1.31 lower to 0.13 lower)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 6 days; assessed with: 7‐point Likert scale  Scale from 0 to 6
Frequency of cough¹	The mean frequency of cough (reduction in frequency of cough score) was ‐1.95.	MD 0.48 score lower  (2.95 lower to 1.99 higher)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Severity of cough¹	The mean severity of cough (reduction in severity of cough score) was ‐1.96.	MD 0.43 score lower  (2.21 lower to 1.35 higher)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Bothersome cough¹	The mean bothersome cough (reduction in bothersome nature of cough score) was ‐1.85.	MD 0.51 score lower  (3.01 lower to 1.99 higher)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on children's sleep¹	The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.68.	MD 0.55 score lower  (1.79 lower to 0.69 higher)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on parents' sleep	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.54.	MD 0.57 score lower  (1.59 lower to 0.45 higher)	‐	102  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Adverse events	Population
Stomachache, nausea, and vomiting	11 per 100	21 per 100  (12 to 35)	RR 1.91  (1.12 to 3.24)	402  (2 RCTs)	⊕⊕⊕⊝  MODERATE²	Follow‐up: mean 6 days
Diarrhoea	13 per 100	12 per 100  (4 to 34)	RR 0.92  (0.33 to 2.55)	102  (1 RCT)	⊕⊕⊝⊝  LOW ³
Tachycardia	2 per 100	4 per 100  (0 to 37)	RR 1.58  (0.15 to 16.86)	102  (1 RCT)	⊕⊕⊝⊝  LOW ³
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence  High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Honey compared to salbutamol for acute cough in children
Patient or population: acute cough in children  Setting: ambulatory  Intervention: honey  Comparison: salbutamol
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Outcomes	Risk with salbutamol	Risk with honey	Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Day 1
Frequency of cough (mean improvement score)¹	The mean frequency of cough (reduction in frequency of cough score) was ‐0.52.	MD 0.26 lower  (3.14 lower to 2.62 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 6 days
Severity of cough (mean improvement score)¹	The mean severity of cough (reduction in severity of cough score) was ‐0.74.	MD 0.1 lower  (0.39 lower to 0.19 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Bothersome cough (mean improvement score)¹	The mean bothersome cough (reduction in bothersome nature of cough score) was ‐1.00.	MD 0.21 lower  (0.9 lower to 0.48 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on children's sleep¹	The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.24.	MD 0.09 higher  (0.05 lower to 0.23 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on parents' sleep¹	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.22.	MD 0.05 higher  (0.03 lower to 0.13 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Day 3
Frequency of cough¹	The mean frequency of cough (reduction in frequency of cough score) was ‐1.34.	MD 0.69 lower  (1.13 lower to 0.25 lower)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 4 days
Severity of cough¹	The mean severity of cough (reduction in severity of cough score) was ‐1.59.	MD 0.34 lower  (0.64 lower to 0.04 lower)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Bothersome cough¹	The mean bothersome cough (reduction in bothersome nature of cough score) was ‐2.08.	MD 0.24 lower  (0.38 lower to 0.1 lower)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on children's sleep¹	The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐2.25.	MD 0.31 higher  (0.13 higher to 0.49 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 6 days
Cough impact on parents' sleep¹	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐2.13.	MD 0.21 higher  (0.06 higher to 0.36 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 4 days
Day 5
Cough duration  assessed (days)	The mean cough duration was 5 days.	MD 0.54 days lower  (0.98 lower to 0.1 lower)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 6 days
Frequency of cough (mean improvement score)¹	The mean frequency of cough (reduction in frequency of cough score) was ‐2.19.	MD 0.54 lower  (1.03 lower to 0.05 lower)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Severity of cough (mean improvement score)¹	The mean severity of cough (reduction in severity of cough score) was ‐2.08.	MD 0.41 lower  (0.78 lower to 0.04 lower)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Bothersome cough (mean improvement score)¹	The mean bothersome cough (reduction in bothersome nature of cough score) was ‐2.47.	MD 0.27 lower  (0.48 lower to 0.06 lower)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on children's sleep¹	The mean cough impact on children's sleep (cough impact on children's sleep score) was ‐2.47.	MD 0.15 higher  (0.04 higher to 0.26 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Cough impact on parents' sleep¹	The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐2.33.	MD 0.04 higher  (0.01 higher to 0.07 higher)	‐	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Adverse events	Population
Stomachache, nausea, and vomiting	30 per 100	53 per 100  (31 to 88)	RR 1.74  (1.04 to 2.92)	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²	Follow‐up: mean 6 days
Rash	9 per 100	2 per 100  (0 to 15)	RR 0.19  (0.02 to 1.63)	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
Tachycardia	2 per 100	4 per 100  (0 to 39)	RR 1.51 (0.14 to 16.10)	100  (1 RCT)	⊕⊕⊝⊝  LOW ³
Diarrhoea	21 per 100	12 per 100  (5 to 30)	RR 0.59  (0.24 to 1.45)	100  (1 RCT)	⊕⊕⊕⊝  MODERATE ²
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence  High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Date	Event	Description
8 February 2018	New citation required but conclusions have not changed	Our conclusions remain unchanged.
8 February 2018	New search has been performed	Searches updated. We included three new trials (Ahmadi 2013; Peixoto 2016; Waris 2014), and excluded three new trials (Ayazi 2017; Baker 2016; Cohen 2017). One study is awaiting classification (IRCT2014090819037N1), and two studies are ongoing (NCT03218696; UMIN000020651).
4 November 2014	New citation required and minor changes	Our conclusions remain unchanged.
4 November 2014	New search has been performed	Searches updated. We included one new trial (Cohen 2012), and excluded two new trials (Ahmed 2013a; Miceli Sopo 2014). Two studies are awaiting classification (IRCT201110247882N1; NCT01356693), and one study is ongoing (IRCT2014090819037N1).
11 January 2012	New search has been performed	Searches updated. We included one new trial (Shadkam 2010).
11 January 2012	New citation required but conclusions have not changed	Our conclusions remain unchanged.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Honey versus dextromethorphan	2		Mean Difference (Random, 95% CI)	Subtotals only
1.1 Frequency of cough (mean reduction in cough frequency)	2	149	Mean Difference (Random, 95% CI)	‐0.07 [‐1.07, 0.94]
1.2 Severity of cough (mean reduction in severity of cough)	2	149	Mean Difference (Random, 95% CI)	‐0.13 [‐1.25, 0.99]
1.3 Bothersome cough (mean reduction in bothersome cough)	1	69	Mean Difference (Random, 95% CI)	0.29 [‐0.56, 1.14]
1.4 Children's sleep (mean reduction in cough impact on sleep score)	2	149	Mean Difference (Random, 95% CI)	0.03 [‐1.12, 1.19]
1.5 Parents' sleep (mean reduction in cough impact on sleep score)	2	149	Mean Difference (Random, 95% CI)	‐0.16 [‐0.84, 0.53]
1.6 Combined cough score (reduction in combined cough score)	1	69	Mean Difference (Random, 95% CI)	2.32 [‐1.24, 5.88]
2 Honey versus diphenhydramine	1		Mean Difference (Random, 95% CI)	Subtotals only
2.1 Frequency of cough (mean reduction in cough frequency)	1	80	Mean Difference (Random, 95% CI)	‐0.57 [‐0.90, ‐0.24]
2.2 Severity of cough (mean reduction in severity of cough)	1	80	Mean Difference (Random, 95% CI)	‐0.6 [‐0.94, ‐0.26]
2.3 Children's sleep (mean reduction in cough impact on sleep score)	1	80	Mean Difference (Random, 95% CI)	‐0.55 [‐0.87, ‐0.23]
2.4 Parents' sleep (mean reduction in cough impact on sleep score)	1	80	Mean Difference (Random, 95% CI)	‐0.48 [‐0.76, ‐0.20]
3 Honey versus no treatment	2		Mean Difference (Random, 95% CI)	Subtotals only
3.1 Frequency of cough (mean reduction in frequency of cough)	2	154	Mean Difference (Random, 95% CI)	‐1.05 [‐1.48, ‐0.62]
3.2 Severity of cough (mean reduction in severity of cough)	2	154	Mean Difference (Random, 95% CI)	‐1.03 [‐1.59, ‐0.47]
3.3 Bothersome cough (mean reduction in bothersome cough)	1	74	Mean Difference (Random, 95% CI)	‐0.93 [‐1.98, 0.12]
3.4 Children's sleep (mean reduction in cough impact on sleep score)	2	154	Mean Difference (Random, 95% CI)	‐1.04 [‐1.57, ‐0.51]
3.5 Parents' sleep (mean reduction in cough impact on sleep score)	2	154	Mean Difference (Random, 95% CI)	‐0.88 [‐1.23, ‐0.52]
3.6 Combined reduction in symptoms score	1	74	Mean Difference (Random, 95% CI)	‐4.31 [‐6.77, ‐1.85]
4 Honey versus placebo (Day 1)	2		Mean Difference (Random, 95% CI)	Subtotals only
4.1 Frequency of cough (mean reduction in frequency of cough)	2	402	Mean Difference (Random, 95% CI)	‐1.62 [‐3.02, ‐0.22]
4.2 Severity of cough (mean reduction in severity of cough)	2	402	Mean Difference (Random, 95% CI)	‐1.07 [‐2.43, 0.30]
4.3 Bothersome cough (mean reduction in bothersome cough)	2	402	Mean Difference (Random, 95% CI)	‐1.40 [‐2.82, 0.03]
4.4 Children's sleep (mean reduction in cough impact on sleep score)	2	402	Mean Difference (Random, 95% CI)	‐1.21 [‐2.61, 0.19]
4.5 Parents' sleep (mean reduction in cough impact on sleep score)	2	402	Mean Difference (Random, 95% CI)	‐1.29 [‐2.71, 0.13]
5 Honey versus placebo (Day 2)	1		Mean Difference (Random, 95% CI)	Subtotals only
5.1 Frequency of cough (mean reduction in frequency of cough)	1	102	Mean Difference (Random, 95% CI)	‐0.71 [‐1.22, ‐0.20]
5.2 Severity of cough (mean reduction in severity of cough)	1	102	Mean Difference (Random, 95% CI)	‐0.63 [‐1.36, 0.10]
5.3 Bothersome cough (mean reduction in bothersome cough)	1	102	Mean Difference (Random, 95% CI)	‐1.11 [‐1.79, ‐0.43]
5.4 Children's sleep (mean reduction in cough impact on sleep score)	1	102	Mean Difference (Random, 95% CI)	‐0.69 [‐1.43, 0.05]
5.5 Parents' sleep (mean reduction in cough impact on sleep score)	1	102	Mean Difference (Random, 95% CI)	‐0.87 [‐1.59, ‐0.15]
6 Honey versus placebo (Day 3)	1		Mean Difference (Random, 95% CI)	Subtotals only
6.1 Frequency of cough (mean reduction in frequency of cough)	1	102	Mean Difference (Random, 95% CI)	‐1.13 [‐1.71, ‐0.55]
6.2 Severity of cough (mean reduction in severity of cough)	1	102	Mean Difference (Random, 95% CI)	‐0.85 [‐1.41, ‐0.29]
6.3 Bothersome cough (mean reduction in bothersome cough)	1	102	Mean Difference (Random, 95% CI)	‐1.33 [‐1.87, ‐0.79]
6.4 Children's sleep (mean reduction in cough impact on sleep score)	1	102	Mean Difference (Random, 95% CI)	‐0.93 [‐1.42, ‐0.44]
6.5 Parents' sleep (mean reduction in cough impact on sleep score)	1	102	Mean Difference (Random, 95% CI)	‐0.88 [‐1.38, ‐0.38]
7 Honey versus placebo (Day 4)	1		Mean Difference (Random, 95% CI)	Subtotals only
7.1 Frequency of cough (mean reduction in frequency of cough)	1	102	Mean Difference (Random, 95% CI)	‐1.16 [‐1.83, ‐0.49]
7.2 Severity of cough (mean reduction in severity of cough)	1	102	Mean Difference (Random, 95% CI)	‐0.88 [‐1.59, ‐0.17]
7.3 Bothersome cough (mean reduction in bothersome cough)	1	102	Mean Difference (Random, 95% CI)	‐0.90 [‐1.76, ‐0.04]
7.4 Children's sleep (mean reduction in cough impact on sleep score)	1	102	Mean Difference (Random, 95% CI)	‐0.7 [‐1.25, ‐0.15]
7.5 Parents' sleep (mean reduction in cough impact on sleep score)	1	102	Mean Difference (Random, 95% CI)	‐0.90 [‐1.51, ‐0.29]
8 Honey versus placebo (Day 5)	1		Mean Difference (Random, 95% CI)	Subtotals only
8.1 Cough duration (mean number of days)	1	102	Mean Difference (Random, 95% CI)	‐0.72 [‐1.31, ‐0.13]
8.2 Frequency of cough (mean reduction in frequency of cough)	1	102	Mean Difference (Random, 95% CI)	‐0.48 [‐2.95, 1.99]
8.3 Severity of cough (mean reduction in severity of cough)	1	102	Mean Difference (Random, 95% CI)	‐0.43 [‐2.21, 1.35]
8.4 Bothersome cough (mean reduction in bothersome cough)	1	102	Mean Difference (Random, 95% CI)	‐0.51 [‐3.01, 1.99]
8.5 Children's sleep (mean reduction in cough impact on sleep score)	1	102	Mean Difference (Random, 95% CI)	‐0.55 [‐1.79, 0.69]
8.6 Parents' sleep (mean reduction in cough impact on sleep score)	1	102	Mean Difference (Random, 95% CI)	‐0.57 [‐1.59, 0.45]
9 Honey versus salbutamol (Day 1)	1		Mean Difference (Random, 95% CI)	Subtotals only
9.1 Frequency of cough (mean reduction in frequency of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.26 [‐3.14, 2.62]
9.2 Severity of cough (mean reduction in severity of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.1 [‐0.39, 0.19]
9.3 Bothersome cough (mean reduction in bothersome cough)	1	100	Mean Difference (Random, 95% CI)	‐0.21 [‐0.90, 0.48]
9.4 Children's sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.09 [‐0.05, 0.23]
9.5 Parents' sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.05 [‐0.03, 0.13]
10 Honey versus salbutamol (Day 2)	1		Mean Difference (Random, 95% CI)	Subtotals only
10.1 Frequency of cough (mean reduction in frequency of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.67 [‐1.35, 0.01]
10.2 Severity of cough (mean reduction in severity of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.42 [‐1.16, 0.32]
10.3 Bothersome cough (mean reduction in bothersome cough)	1	100	Mean Difference (Random, 95% CI)	‐0.27 [‐0.52, ‐0.02]
10.4 Children's sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.17 [‐0.04, 0.38]
10.5 Parents' sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.03 [‐0.00, 0.06]
11 Honey versus salbutamol (Day 3)	1		Mean Difference (Random, 95% CI)	Subtotals only
11.1 Frequency of cough (mean reduction in frequency of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.69 [‐1.13, ‐0.25]
11.2 Severity of cough (mean reduction in severity of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.34 [‐0.64, ‐0.04]
11.3 Bothersome cough (mean reduction in bothersome cough)	1	100	Mean Difference (Random, 95% CI)	‐0.24 [‐0.38, ‐0.10]
11.4 Children's sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.31 [0.13, 0.49]
11.5 Parents' sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.21 [0.06, 0.36]
12 Honey versus salbutamol (Day 4)	1		Mean Difference (Random, 95% CI)	Subtotals only
12.1 Frequency of cough (mean reduction in frequency of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.61 [‐0.96, ‐0.26]
12.2 Severity of cough (mean reduction in severity of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.43 [‐0.78, ‐0.08]
12.3 Bothersome cough (mean reduction in bothersome cough)	1	100	Mean Difference (Random, 95% CI)	‐0.3 [‐0.59, ‐0.01]
12.4 Children's sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.22 [0.05, 0.39]
12.5 Parents' sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.15 [0.04, 0.26]
13 Honey versus salbutamol (Day 5)	1		Mean Difference (Random, 95% CI)	Subtotals only
13.1 Cough duration (mean number of days)	1	100	Mean Difference (Random, 95% CI)	‐0.54 [‐0.98, ‐0.10]
13.2 Frequency of cough (mean reduction in frequency of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.54 [‐1.03, ‐0.05]
13.3 Severity of cough (mean reduction in severity of cough)	1	100	Mean Difference (Random, 95% CI)	‐0.41 [‐0.78, ‐0.04]
13.4 Bothersome cough (mean reduction in bothersome cough)	1	100	Mean Difference (Random, 95% CI)	‐0.27 [‐0.48, ‐0.06]
13.5 Children's sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.15 [0.04, 0.26]
13.6 Parents' sleep (mean reduction in cough impact on sleep score)	1	100	Mean Difference (Random, 95% CI)	0.04 [0.01, 0.07]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Cough frequency (mean reduction in frequency)	4		Mean Difference (Fixed, 95% CI)	Subtotals only
1.1 Honey	4	357	Mean Difference (Fixed, 95% CI)	‐1.71 [‐2.28, ‐1.13]
1.2 Dextromethorphan	2	74	Mean Difference (Fixed, 95% CI)	‐1.54 [‐2.30, ‐0.78]
1.3 Diphenhydramine	1	40	Mean Difference (Fixed, 95% CI)	‐1.73 [‐2.72, ‐0.74]
1.4 Placebo	2	120	Mean Difference (Fixed, 95% CI)	‐0.99 [‐1.79, ‐0.18]
1.5 Salbutamol Day 1	1	43	Mean Difference (Fixed, 95% CI)	‐0.52 [‐6.28, 5.24]
1.6 No treatment	2	79	Mean Difference (Fixed, 95% CI)	‐0.98 [‐1.38, ‐0.59]
1.7 Buckwheat honey	1	35	Mean Difference (Fixed, 95% CI)	‐1.89 [‐2.96, ‐0.81]
1.8 Natural honey from Kafi‐Abad (Iran)	1	40	Mean Difference (Fixed, 95% CI)	‐2.16 [‐3.40, ‐0.92]
1.9 Eucalyptus honey	1	75	Mean Difference (Fixed, 95% CI)	‐1.77 [‐3.22, ‐0.32]
1.10 Labiatae honey	1	75	Mean Difference (Fixed, 95% CI)	‐1.82 [‐3.30, ‐0.34]
1.11 Citrus honey	1	75	Mean Difference (Fixed, 95% CI)	‐1.95 [‐3.55, ‐0.35]
1.12 Salbutamol Day 5	1	43	Mean Difference (Fixed, 95% CI)	‐2.19 [‐3.55, ‐0.83]
1.13 African honey Day 5	1	57	Mean Difference (Fixed, 95% CI)	‐2.65 [‐4.32, ‐0.98]
1.14 Placebo Day 5	1	45	Mean Difference (Fixed, 95% CI)	‐1.95 [‐4.42, 0.52]
2 Severity of cough (mean reduction in severity)	4		Mean Difference (Fixed, 95% CI)	Subtotals only
2.1 Honey	4	357	Mean Difference (Fixed, 95% CI)	‐1.65 [‐2.39, ‐0.91]
2.2 Dextromethorphan	2	74	Mean Difference (Fixed, 95% CI)	‐1.52 [‐2.24, ‐0.80]
2.3 Diphenhydramine	1	40	Mean Difference (Fixed, 95% CI)	‐1.83 [‐2.88, ‐0.78]
2.4 Salbutamol Day 1	1	43	Mean Difference (Fixed, 95% CI)	‐0.74 [‐2.87, 1.39]
2.5 No treatment	2	79	Mean Difference (Fixed, 95% CI)	‐1.13 [‐1.54, ‐0.72]
2.6 Placebo	2	120	Mean Difference (Fixed, 95% CI)	‐0.80 [‐1.47, ‐0.13]
2.7 Buckwheat honey	1	35	Mean Difference (Fixed, 95% CI)	‐1.80 [‐2.88, ‐0.72]
2.8 Natural honey from Kafi‐Abad (Iran)	1	40	Mean Difference (Fixed, 95% CI)	‐2.33 [‐3.67, ‐0.99]
2.9 Eucalyptus honey	1	75	Mean Difference (Fixed, 95% CI)	‐1.78 [‐2.82, ‐0.74]
2.10 Labiatae honey	1	75	Mean Difference (Fixed, 95% CI)	‐1.94 [‐3.07, ‐0.81]
2.11 Citrus honey	1	75	Mean Difference (Fixed, 95% CI)	‐1.77 [‐2.74, ‐0.80]
2.12 Salbutamol Day 5	1	43	Mean Difference (Fixed, 95% CI)	‐2.08 [‐4.21, 0.05]
2.13 African honey Day 5	1	57	Mean Difference (Fixed, 95% CI)	‐2.62 [‐5.04, ‐0.20]
2.14 Placebo Day 5	1	45	Mean Difference (Fixed, 95% CI)	‐1.96 [‐3.74, ‐0.18]
3 Bothersome cough (mean reduction in bothersome cough)	3		Mean Difference (Fixed, 95% CI)	Subtotals only
3.1 Honey	3	317	Mean Difference (Fixed, 95% CI)	‐2.22 [‐3.24, ‐1.21]
3.2 Dextromethorphan	1	34	Mean Difference (Fixed, 95% CI)	‐1.94 [‐3.05, ‐0.83]
3.3 Salbutamol Day 1	1	43	Mean Difference (Fixed, 95% CI)	‐1.0 [‐4.28, 2.28]
3.4 No treatment	1	39	Mean Difference (Fixed, 95% CI)	‐1.30 [‐2.07, ‐0.53]
3.5 Placebo	2	120	Mean Difference (Fixed, 95% CI)	‐1.08 [‐2.06, ‐0.10]
3.6 Buckwheat honey	1	35	Mean Difference (Fixed, 95% CI)	‐2.23 [‐3.50, ‐0.96]
3.7 Eucalyptus honey	1	75	Mean Difference (Fixed, 95% CI)	‐2.0 [‐3.82, ‐0.18]
3.8 Labiatae honey	1	75	Mean Difference (Fixed, 95% CI)	‐2.07 [‐4.03, ‐0.11]
3.9 Citrus honey	1	75	Mean Difference (Fixed, 95% CI)	‐2.16 [‐4.20, ‐0.12]
3.10 Salbutamol Day 5	1	43	Mean Difference (Fixed, 95% CI)	‐2.47 [‐4.73, ‐0.21]
3.11 African honey Day 5	1	57	Mean Difference (Fixed, 95% CI)	‐2.74 [‐5.27, ‐0.21]
3.12 Placebo Day 5	1	45	Mean Difference (Fixed, 95% CI)	‐1.85 [‐3.56, ‐0.14]
4 Children's sleep (mean reduction in cough impact on sleep score)	4		Mean Difference (Random, 95% CI)	Subtotals only
4.1 Honey	4	357	Mean Difference (Random, 95% CI)	‐2.23 [‐2.87, ‐1.59]
4.2 Dextromethorphan	2	74	Mean Difference (Random, 95% CI)	‐1.75 [‐2.46, ‐1.04]
4.3 Diphenhydramine	1	40	Mean Difference (Random, 95% CI)	‐1.64 [‐2.58, ‐0.70]
4.4 No treatment	2	79	Mean Difference (Random, 95% CI)	‐1.28 [‐1.81, ‐0.76]
4.5 Placebo	2	120	Mean Difference (Random, 95% CI)	‐1.03 [‐2.05, 0.00]
4.6 Salbutamol Day 5	1	43	Mean Difference (Random, 95% CI)	‐2.47 [‐3.84, ‐1.10]
4.7 African honey Day 5	1	57	Mean Difference (Random, 95% CI)	‐2.32 [‐3.63, ‐1.01]
4.8 Placebo Day 5	1	45	Mean Difference (Random, 95% CI)	‐1.68 [‐2.63, ‐0.73]
5 Parents' sleep (mean reduction in cough impact on sleep score)	4		Mean Difference (Fixed, 95% CI)	Subtotals only
5.1 Honey	4	357	Mean Difference (Fixed, 95% CI)	‐2.25 [‐2.89, ‐1.61]
5.2 Dextromethorphan	2	74	Mean Difference (Fixed, 95% CI)	‐1.97 [‐2.77, ‐1.17]
5.3 Diphenhydramine	1	40	Mean Difference (Fixed, 95% CI)	‐1.89 [‐2.97, ‐0.81]
5.4 No treatment	2	79	Mean Difference (Fixed, 95% CI)	‐1.46 [‐2.06, ‐0.87]
5.5 Placebo	2	120	Mean Difference (Fixed, 95% CI)	‐1.44 [‐2.28, ‐0.61]
5.6 Salbutamol Day 5	1	43	Mean Difference (Fixed, 95% CI)	‐2.33 [‐3.91, ‐0.75]
5.7 African honey Day 5	1	57	Mean Difference (Fixed, 95% CI)	‐2.29 [‐3.86, ‐0.72]
5.8 Placebo Day 5	1	45	Mean Difference (Fixed, 95% CI)	‐1.54 [‐2.60, ‐0.48]
6 Combined reduction in symptoms score	3		Mean Difference (Fixed, 95% CI)	Subtotals only
6.1 Honey	3	317	Mean Difference (Fixed, 95% CI)	‐10.60 [‐14.43, ‐6.77]
6.2 Dextromethorphan	1	34	Mean Difference (Fixed, 95% CI)	‐8.39 [‐10.95, ‐5.84]
6.3 No treatment	1	39	Mean Difference (Fixed, 95% CI)	‐6.41 [‐8.82, ‐3.99]
6.4 Placebo	2	132	Mean Difference (Fixed, 95% CI)	‐7.11 [‐10.78, ‐3.44]
6.5 Honey Day 5	1	57	Mean Difference (Fixed, 95% CI)	‐12.68 [‐14.06, ‐11.30]
6.6 Placebo Day 5	1	45	Mean Difference (Fixed, 95% CI)	‐8.69 [‐14.17, ‐3.21]
6.7 Salbutamol Day 5	1	43	Mean Difference (Fixed, 95% CI)	‐11.37 [‐17.55, ‐5.19]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Honey versus dextromethorphan	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
1.1 Nervousness, insomnia, hyperactivity	2	149	Risk Ratio (M‐H, Fixed, 95% CI)	2.94 [0.74, 11.71]
1.2 Stomachache, nausea, and vomiting	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	4.86 [0.24, 97.69]
1.3 Drowsiness	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	2.92 [0.12, 69.20]
2 Honey versus diphenhydramine	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 2.68]
2.1 Somnolence	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 2.68]
3 Honey versus placebo	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.1 Stomachache, nausea, and vomiting	2	402	Risk Ratio (M‐H, Fixed, 95% CI)	1.91 [1.12, 3.24]
3.2 Diarrhoea	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.33, 2.55]
3.3 Tachycardia	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.15, 16.86]
4 Honey versus salbutamol	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
4.1 Stomachache, nausea, and vomiting	1	100	Risk Ratio (M‐H, Random, 95% CI)	1.74 [1.04, 2.92]
4.2 Rash	1	100	Risk Ratio (M‐H, Random, 95% CI)	0.19 [0.02, 1.63]
4.3 Tachycardia	1	100	Risk Ratio (M‐H, Random, 95% CI)	1.51 [0.14, 16.10]
4.4 Diarrhoea	1	100	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.24, 1.45]
5 Honey versus no treatment	2	302	Odds Ratio (M‐H, Fixed, 95% CI)	6.99 [1.55, 31.58]
5.1 Nervousness, insomnia, hyperactivity	2	154	Odds Ratio (M‐H, Fixed, 95% CI)	9.40 [1.16, 76.20]
5.2 Stomachache, nausea, and vomiting	1	74	Odds Ratio (M‐H, Fixed, 95% CI)	5.90 [0.27, 127.14]
5.3 Drowsiness	1	74	Odds Ratio (M‐H, Fixed, 95% CI)	3.43 [0.14, 87.09]

Methods	Study design: RCT Study duration: 2010 to November 2012
Participants	Setting: a paediatric outpatient clinic, Shariatee Hospital, Bandar Abbas Country: Iran Health status: viral upper respiratory tract infection with complaints of sneezing, blocked nose, sore throat, cough, mild headache Number: treatment (63); control (63) Age (mean ± SD) treatment: 45.21 ± 11.39 months control: 43.98 ± 11.95 months Sex (M/F): 60/66 treatment (M/F): 27/36 control (M/F): 33/30 Exclusion criteria Onset of otitis or sinusitis symptoms; onset of symptoms of lower respiratory tract involvement; adding a bacterial infection (purulent nasal discharge, high fever, difficulty breathing, periorbital oedema, facial pain); not using recommended treatments; adding other drugs to recommended treatment; conflicting reports of the carers of the participants
Interventions	Treatment group Intervention: honey (Mahram) Dose, duration, frequency, administration: honey was placed in glasses similar to those belonging to diphenhydramine and with a similar concentration, mixed with distilled lukewarm water, administered 3 times a day, with last dose given an hour before sleeping. Control group Intervention: 5 mg/kg diphenhydramine syrup Dose, duration, frequency, administration: 5 mg/kg body weight, 3 times a day, with last dose given an hour before sleeping Honey was given in the same volume, frequency, and duration of use as diphenhydramine.
Outcomes	Severity of cough Frequency of cough
Notes	Funding source: unknown Contact with study authors for additional information: we contacted authors for additional information but received no response. A volunteer translated the study from Farsi to English. A 7‐point Likert‐like scale was used for cough assessment.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Not described but likely done. Randomisation was done by the hospital pharmacist who was not involved in the study.
Allocation concealment (selection bias)	Low risk	Not described but probably done. Quote: "The classification of patients was done by the hospital pharmacist"
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Honey was placed in glasses similar to those belonging to diphenhydramine and with a similar concentration, mixed with distilled lukewarm water. The honey and diphenhydramine mixtures were prepared by the pharmacist, who was not part of the study. The paediatricians and parents were unaware of the nature of the treatment each child received.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Quote: "the treating doctor and the mother were unaware of the nature of the medication (honey or diphenhydramine)"; "In order to prevent the confounding factor of mother’s anxiety or her personal situation, her reports were only accepted if they were corroborated by the reports of a third person close to the child"
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All children randomised to treatment arms completed the 2‐day study.
Selective reporting (reporting bias)	Low risk	Both outcomes listed in the methods section were reported.
Other bias	Unclear risk	Results were presented as the proportion of children with reduced symptom cough instead of the actual mean symptom scores. Furthermore, the scale used for measurement was not clear (a 7‐point Likert‐like scale was used for cough assessment). The protocol was registered retrospectively after completion of the study.

Methods	Study design: RCT Study duration: January 2009 to December 2009
Participants	Setting: 6 paediatric community clinics Country: Israel Health status: children with upper respiratory infection who "were ill with a mean ± SD of 2.8 ± 2.0 days before enrolment". Upper respiratory infection was "defined by the presence of cough and rhinorrhea of #7 days’ duration". Number (total = 300): treatment 1, eucalyptus honey (N = 75) treatment 2, citrus honey (N = 75) treatment 3, Labiatae honey (N = 75) control, placebo (N = 75) Age: median age of children who completed the study was 29 months (range 12 to 71 months). treatment: eucalyptus honey: mean 27.5 months ± 13.9 citrus honey: mean age 29 months ± 13.5 Labiatae honey: mean age 30 months ± 16.6 control: mean age 29 months ± 14.9 Sex: unclear Exclusion criteria Quote: "children were excluded if they had signs or symptoms of asthma, pneumonia, laryngotracheobronchitis, sinusitis, and/or allergic rhinitis. Children were also excluded if they had used any cough or cold medication or honey on the night before entering the study"
Interventions	Treatment group Intervention: eucalyptus honey, citrus honey, or Labiatae honey (3 intervention arms) Dose, duration, frequency, administration: single 10 g dose administered 30 minutes before bedtime Control group Intervention: silan (date) extract (similar structure, colour, and taste to honey) Dose, duration, frequency, administration: single 10 g dose administered 30 minutes before bedtime
Outcomes	Cough frequency Cough severity Bothersome nature of cough Child and parent sleep quality The combined score of these 4 measures
Notes	Funding source: quote: "Supported in part by a research grant from Israel Ambulatory Paediatric Association, Maternal Infant Nutrition Research Institute and the Honey Board of Israel" Contact with study authors for additional information: we contacted the authors to confirm the proportion of boys to girls of the 300 children randomised. Authors did not respond to our query.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was in blocks of 4.
Allocation concealment (selection bias)	Low risk	The envelopes containing the codes for the study preparations were stored at the office of the Ministry of Agriculture, Extension service, Beekeeping Department and were not opened until after the statistical analysis was completed.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	The 3 honeys and the placebo were prepared by someone not involved in the study; interventions were packed in small plastic containers marked A, B, C, and D and distributed to the paediatric community clinics. Silan date extract was used as a placebo because its structure, brown colour, and taste are similar to that of honey. The parents, physicians, and investigators did not know the content of the preparation that was dispensed.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	The parents, physicians, and investigators did not know the content of the preparation that was dispensed. Interventions were packed in small plastic containers marked A, B, C, and D and distributed to the paediatric community clinics. Silan date extract was used as a placebo because its structure, brown colour, and taste are similar to that of honey.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	14 (19%), 13 (18%), 2 (3%), and 4 (5%) children were lost to follow‐up in the eucalyptus honey, citrus honey, Labiatae honey, and placebo groups, respectively. The authors stated that the reasons for loss to follow‐up were unknown. However, attrition was significantly high in the eucalyptus honey and citrus honey groups. It is unclear if the reasons for attrition in the treatment groups were related to the study or not and if the reasons were similar.
Selective reporting (reporting bias)	Low risk	All outcomes listed in the protocol were reported.
Other bias	Low risk	Not detected

Methods	RCT
Participants	Setting: a single outpatient general paediatric practice Country: USA Health status: "The URIs were characterized by the presence of rhinorrhea and cough for 7 or fewer days’ duration. Other symptoms may have included but were not limited to congestion, fever, sore throat, myalgias, and headache" (p. 1141) Number (total = 108): honey (N = 35) control: dextromethorphan (N = 34) no treatment (N = 39) Age: 2 to 18 years; median age of the 105 children completing the study was 5.22 years (range 2.22 to 16.92 years) treatment (median ± interquartile range, years): honey = 5.43 ± 3.81 control (median ± interquartile range, years): dextromethorphan = 4.42 ± 3.83 no treatment = 5.22 ± 4.33 Sex: unclear Exclusion criteria Quote: "patients were excluded if they had signs or symptoms of a more treatable disease (e.g., asthma, pneumonia, laryngotracheobronchitis, sinusitis, allergic rhinitis). They were also ineligible when they had a history of reactive airways disease, asthma, or chronic lung disease or were using a drug known to inhibit the metabolism of dextromethorphan, such as selective serotonin reuptake inhibitors. Subjects were also excluded if on the prior evening they had taken a medication that included an antihistamine or dextromethorphan hydrobromide within 6 hours of bedtime or dextromethorphan polistirex within 12 hours of bedtime on the evening prior to or on the day of enrolment" (p. 1141)
Interventions	Treatment group Intervention: buckwheat honey Dose, duration, frequency, administration: "For the honey group, the volume of honey dispensed was equivalent to the age‐driven volume dispensed for DM [dextromethorphan]" Control group Intervention: "artificially honey‐flavoured DM [dextromethorphan], (17 mg/5 mL prepared using DM hydrobromide powder [100% pure United States Pharmacopeia grade], artificial honey flavoring, coloring, stevia liquid extract, methocel, and simple syrup [Professional Compounding Centers of America, Houston, Texas])", no treatment = empty syringe Dose, duration, frequency, administration: "dosage for DM [dextromethorphan] approximated typical OTC label recommendations, with children aged 2 to 5 years receiving 8.5 mg/dose (1/2 teaspoon), children aged 6 to 11 years receiving 17 mg/dose (1 teaspoon), and children aged 12 to 18 years receiving 34 mg/dose (2 teaspoons). Of note, these concentrations slightly exceed typical OTC products, which contain 15 mg/5 mL, and were the result of the compounding process but may be more likely to achieve a beneficial effect based on our previous analyses" Parents were instructed that their child’s treatment could be given with a non‐caffeinated beverage and should be administered within 30 minutes of the child going to sleep. Intervention and control were in a 10‐millilitre opaque syringe and kept in brown paper bags.
Outcomes	Cough frequency Cough severity Bothersome nature of cough Cough impact on sleep quality for child and parent The combined score of these 4 measures
Notes	Funding source: "this study was supported by an unrestricted research grant from the National Honey Board, an industry‐funded agency of the USA Department of Agriculture" Contact with study authors for additional information: we contacted the lead author for additional information on the proportion of boys to girls of the 108 children randomised and other missing data. Authors responded that they could not provide the information because they no longer have the data.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Not described but probably done. Quote: "The randomisation sequence was constructed by a statistician not affiliated with the study and was then used by the study coordinators to assign treatment group"
Allocation concealment (selection bias)	Low risk	Not described but probably done. Treatment allocation was concealed in 10‐millilitre opaque syringe and kept in brown paper bags.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	The syringes used for all 3 treatment groups were opaque and placed in a brown paper bag to conceal the treatments from the investigators. The no‐treatment group was not blinded to their treatment, but the honey and dextromethorphan arms were blinded.
Blinding of outcome assessment (detection bias)   All outcomes	High risk	Although all participants were given syringes in brown paper bags, the no‐treatment group had empty syringes, which could influence the assessment of the outcome.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	2 children from the no‐treatment group were lost to follow‐up; 1 was withdrawn from the dextromethorphan group because the participant did not take the treatment.
Selective reporting (reporting bias)	Low risk	All outcomes were adequately reported.
Other bias	Low risk	It is unclear whether any of the no‐treatment group revealed to any of the assessors during phone conversations that they were given no treatment. Children lost to follow‐up or withdrawn were not included in the final analysis.

Methods	RCT
Participants	Setting: a paediatric service of Clinica Amaury Coutinho, linked to Recife City Hall Country: Brazil Health status: "irritative cough for at least 24 hours, which led to the need for medical consultation, participated in the study. Patients should have acute cough due to viral upper airway infection, thus considered due to the presence of mild fever or fever associated with hyaline or catarrhal rhinorrhea, lasting less than 72 hours, without clinical manifestations of associated bronchospasm" Number (total = 60): treatment: honey (N = 29) control: bromelin (N = 31) Age: age in years, mean (25 to 75 percentiles): treatment: honey: mean 5.6 years (2.0 to 7.5 years) control: bromelin: mean 5.3 years (3.0 to 7.5 years) Sex of children who completed study (M/F): treatment: honey (13/16) control: bromelin (13/18) Exclusion criteria Children with history of obstructive pulmonary disease, cystic fibrosis, neuropathies, heart disease, diabetes, or identifiable primary or secondary immunodeficiencies
Interventions	Treatment group Intervention: honey Dose, duration, frequency, administration: children up to 20 kg received 5 mL; for those weighing > 20 kg, 1 mL was administered for every 5 kg additional weight. Control group Intervention: the combination of honey and Ananas comosus extract HBS19820501 (rich in bromelin) as syrup formulation Dose, duration, frequency, administration: children up to 20 kg received 5 mL; for those weighing > 20 kg, 1 mL was administered for every 5 kg additional weight. Quote: "the quality of the honey was certified in both groups and approved by the regulatory agencies and the National Health Surveillance Agency (Anvisa) for sale; the honey had been recently produced and underwent strict bacteriological control"
Outcomes	Cough frequency Reduction in cough severity
Notes	Funding source: Hebron Indústrias Químicas
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was carried out according to a table generated in Microsoft Excel.
Allocation concealment (selection bias)	Low risk	Not described but very likely. Treatments were labelled A and B. Quote: "Neither the investigator nor the patient, nor the family knew which product was used"; "The treatment groups were revealed only after the analysis of the study results"
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Quote: "neither the investigator nor the patient, nor the family knew which product was used. The treatment groups were revealed only after the analysis of the study results"
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Quote: "neither the investigator nor the patient, nor the family knew which product was used. The treatment groups were revealed only after the analysis of the study results"
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All participants randomised were included in the final analysis.
Selective reporting (reporting bias)	Low risk	All outcomes listed in the study protocol and methods section were reported.
Other bias	Unclear risk	Used an unvalidated 5‐point cough scale that differed from the cough scale used by the other included studies

Methods	RCT
Participants	Setting: the paediatric casualty of the Aga Khan University Hospital Nairobi. This is a national tertiary referral and teaching hospital serving the middle‐ and upper‐income society in Nairobi and its environment. Country: Kenya Health status: an uncomplicated acute upper respiratory infection (authors did not define acute upper respiratory infection) Number (total = 145): treatment: honey (N = 57) control: salbutamol (N = 43) placebo (N = 45) Age: 1 to 12 years treatment: not clear control: not clear Sex of children who completed study (M/F): honey (30/24) control: salbutamol (unclear) placebo: (unclear) Exclusion criteria Prior use (48 hours) of any cough mixture, study agents, oral antihistamines, nasal decongestants, steroids, or antibiotics. Other exclusions were any past history of atopy, asthma, or any chronic lung disease as well as hospitalisation for lower respiratory tract infection in the past 6 months.
Interventions	Treatment group Intervention: the darkest locally available honey was used. Dose, duration, frequency, administration: 2.5 mL (age 1 to 2 years), 5 mL (age 2 to 6 years), 7.5 mL (age 6 to 12 years); all were administered 3 times daily for 5 days Control group Intervention: salbutamol has 2 mg of active ingredient per 5 mL. placebo was a brown‐coloured sugar and alcohol‐free syrup with an inert thickening agent whose ingredients included sodium citrate, citric acid monohydrate hypromellose, sodium benzoate, saccharin sodium, sodium chloride, caramel colour, and water. Dose, duration, frequency, administration: 2.5 mL (age 1 to 2 years), 5 mL (age 2 to 6 years), 7.5 mL (age 6 to 12 years); all were administered 3 times daily for 5 days
Outcomes	Cough frequency Cough severity Bothersome cough Cough effect on children's sleep Cough effect on parents' sleep Combined symptom score
Notes	Funding source: Universal Corporation Ltd prepared all study drugs at no cost. Contact with study authors for additional information: we contacted the authors for additional information on cough scores and mean age of children randomised. It is unclear if the salbutamol was oral or inhaled. It was most likely oral because parents were given all study drugs to administer to their children at home.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Dispensing study drugs was undertaken following a random order previously generated by a statistician not involved in care of study participants.
Allocation concealment (selection bias)	Low risk	Not described, but risk of bias unlikely. All 3 study drugs were prepared, bottled, packaged, and labelled as Study Drug A, B, and C by Universal Corporation Ltd, who also held the code until after statistical analysis was completed.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	All 3 study drugs were prepared, bottled, packaged, and labelled as Study Drug A, B, and C by Universal Corporation Ltd, who also held the code until after statistical analysis was completed.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	All 3 study drugs were prepared, bottled, packaged, and labelled as Study Drug A, B, and C by Universal Corporation Ltd, who also held the code until after statistical analysis was completed.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	13%, 7%, and 5% of children in the placebo, honey, and salbutamol groups, respectively, were lost to follow‐up or were in violation of study protocol. It is unclear if the reasons for not completing the study were the same across study groups. It is possible that more participants in the placebo group left because their condition worsened.
Selective reporting (reporting bias)	Low risk	Not detected
Other bias	Low risk	Unlikely

Study	Reason for exclusion
Ahmed 2013a	Not an RCT; this was a feasibility study of honey for the treatment of cough in children
Ayazi 2017	Quasi‐RCT
Baker 2016	Not an RCT; commentary on a previous version of this review (Oduwole 2014a)
Cohen 2017	Wrong intervention: compared polysaccharide‐resin‐honey to carbocysteine syrup. The study examined honey‐based cough syrup (polysaccharide‐resin‐honey) versus a non‐honey‐based cough syrup (carbocysteine syrup). We would have included this study if the comparisons had been polysaccharide‐resin‐honey versus honey alone/polysaccharide‐resin alone or carbocysteine syrup + honey versus carbocysteine syrup alone.
Gilbert 2008	Not an RCT
Miceli Sopo 2014	Wrong intervention: compared honey and milk versus dextromethorphan and honey and milk versus levodropropizine
Warren 2007	Not an RCT

Methods	Randomised clinical trial
Participants	Children aged 2 to 12 years
Interventions	2 types of honey versus diphenhydramine
Outcomes	Cough frequency, bothersome nature of cough, and severity
Notes	Completed

Trial name or title	Comparison of a protective cough syrup against placebo on night cough in children 1 to 5 years coughing since 1 to 2 days due to common cold
Methods	Randomised controlled trial
Participants	Children aged 1 to 5 years (i.e. 1 day before the 6th birthday, males and females) Inclusion criteria: cough attributed to infection of the upper respiratory tract present in the child for not more than 2 days
Interventions	Cough syrup containing specific plant extracts (Poliflav MA) and honey versus placebo
Outcomes	Primary night cough frequency score reduction Secondary night cough bothersome score reduction night cough intensity score reduction reduction of influence of cough on child sleep score reduction of influence of cough on combined night score reduction of influence of cough on parent sleep score (Time frame: First and only night of treatment)
Starting date	September 2017
Contact information	Prof Herman A Cohen Email: hermanc@clalit.org.il Affiliation: Clalit Health Services
Notes	This study is not yet open for participant recruitment (November 2017).

Trial name or title	Effectiveness of honey and expectorant for nocturnal cough in children with acute upper respiratory infection: a prospective interventional study
Methods	Parallel randomised
Participants	Children aged 2 to 16 years Inclusion criteria: Patient diagnosed with acute upper respiratory infection with cough for 7 or fewer days duration Nocturnal cough score 3 or more (using a 7‐point Likert scale)
Interventions	Honey (5 g for those age 2 to 5 years, 10 g for those aged 6 years and above) orally before bedtime for a week versus carbocysteine (30 mg/kg/day) and ambroxol (0.9 mg/kg/day) orally for a week
Outcomes	Primary outcome: change in frequency of nocturnal cough on the next day when honey or expectorant had been given prior to bedtime compared to that on the first day of presentation when no medication had been given Secondary outcomes: Change in severity of nocturnal cough, bothersome cough, appetite, and quality of sleep at night on the next day when honey or expectorant had been given prior to bedtime compared to that on the first day of presentation when no medication had been given. Improvement of nocturnal cough 1 week after honey or expectorant had been given prior to bedtime compared to that on the first day of presentation when no medication had been given
Starting date	25 January 2016
Contact information	Name: Kazushi Agata; Shun Kishibe Address: 1163 Tatemachi, Hachioji, Tokyo, Japan; 2‐8‐29 Musashidai, Fuchu‐shi, Tokyo, Japan Email: tokyoseki2016@gmail.com; jemstone625@gmail.com Affiliation: Tokyo Medical University Hachioji Medical Center Pediatrics; Tokyo Metropolitan Children's Medical Center Pediatric Emergency Medicine
Notes

PERMALINK

Honey for acute cough in children

Olabisi Oduwole

Ekong E Udoh

Angela Oyo‐Ita

Martin M Meremikwu

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

1. Pre‐ and postintervention comparison of honey on cough frequency and severity expressed as medians.

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

GRADE and 'Summary of findings' table

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Results

Description of studies

Results of the search

1.

Included studies

Study populations

Study settings

Interventions

Comparators

Study funding sources

Excluded studies

Studies awaiting classification

Ongoing studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Summary of findings for the main comparison. Honey compared to dextromethorphan for acute cough in children.

Summary of findings 2. Honey compared to diphenhydramine for acute cough in children.

Summary of findings 3. Honey compared to no treatment for acute cough in children.

Summary of findings 4. Honey compared to placebo for acute cough in children.

Summary of findings 5. Honey compared to salbutamol for acute cough in children.

Primary outcomes

1. Duration of cough

1.13. Analysis.

1.8. Analysis.

2. Symptomatic relief of cough (frequency of cough, reduction in severity, and less bothersome)

2.1 Frequency of cough (pre‐ and postintervention comparison)