Content uploaded by Herman Avner
Author content
All content in this area was uploaded by Herman Avner on Dec 12, 2015
Content may be subject to copyright.
Effect of Honey on Nocturnal Cough and Sleep Quality:
A Double-blind, Randomized, Placebo-Controlled Study
WHAT’S KNOWN ON THIS SUBJECT: Honey is recommended as
a cough medication by the World Health Organization. To date, the
efficacy of this treatment has been shown in 2 studies: one tested
only buckwheat honey and the other study was not blinded.
WHAT THIS STUDY ADDS: In a randomized controlled trial, we
compared 3 types of honey versus placebo as a treatment of
upper respiratory tract infection–associated cough. These types
of honey were superior to placebo in alleviating cough.
abstract
OBJECTIVES: To compare the effects of a single nocturnal dose of 3
honey products (eucalyptus honey, citrus honey, or labiatae honey) to
placebo (silan date extract) on nocturnal cough and difficulty sleeping
associated with childhood upper respiratory tract infections (URIs).
METHODS: A survey was administered to parents on 2 consecutive
days, first on the day of presentation, when no medication had been
given the previous evening, and the following day, when the study prep-
aration was given before bedtime, based on a double-blind randomization
plan. Participants included 300 children aged 1 to 5 years with URIs,
nocturnal cough, and illness duration of #7daysfrom6general
pediatric community clinics. Eligible children received a single dose of
10 g of eucalyptus honey, citrus honey, labiatae honey, or placebo
administered 30 minutes before bedtime. Main outcome measures
were cough frequency, cough severity, bothersome nature of cough,
and child and parent sleep quality.
RESULTS: In all 3 honey products and the placebo group, there was
a significant improvement from the night before treatment to the night
of treatment. However, the improvement was greater in the honey
groups for all the main outcome measures.
CONCLUSIONS: Parents rated the honey products higher than the silan
date extract for symptomatic relief of their children’s nocturnal cough
and sleep difficulty due to URI. Honey may be a preferable treatment
for cough and sleep difficulty associated with childhood URI. Pediatrics
2012;130:465–471
AUTHORS: Herman Avner Cohen, MD,
a
,
b
Josef Rozen, MD,
b
,
c
,
†
Haim Kristal, MD,
b
,
d
Yoseph Laks, MD,
b
,
e
Mati Berkovitch,
MD,
b
,
f
Yos e f Uzi el, MD ,
b
,
g
Eran Kozer, MD,
b
,
h
Avishalom
Pomeranz, MD,
b
,
i
and Haim Efrat
j
a
Pediatric Ambulatory Community Clinic, Petach Tikva, Israel;
b
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;
c
Pediatric Ambulatory Community Clinic, Kefar Saba, Israel;
d
Pediatric Ambulatory Community Clinic, Kiryat Shmone, Israel;
e
Pediatric Ambulatory Community Clinic, Ramat Aviv, Israel;
f
Clinical Pharmacology Unit, Assaf Harofeh Medical Center,
Zerifin, Israel;
g
Department of Pediatrics, Meir Medical Center,
Kfar Saba, Israel;
h
Pediatric Emergency Unit, Assaf Harofeh
Medical Center, Zerifin, Israel;
i
Department of Pediatrics, Meir
Medical Center, Kfar Saba, Israel; and
j
Zerifin Breeding Apiary,
Volcani Agricultural Research Center, Rechovot, Israel
KEY WORDS
cough, children, honey
ABBREVIATIONS
FDA—Food and Drug Administration
OTC—over-the-counter
URI—upper respiratory tract infection
†
Deceased.
Dr Cohen was responsible for conception and design of study,
data acquisition, analysis and interpretation of data, and he
drafted and revised the article and approved the final version;
Dr Rozen was responsible for data acquisition, data analysis and
interpretation, and critical revision of the article; Drs Kristal,
Laks, Berkovitch, Uziel, Kozer, and Pomeranz were responsible
for data acquisition, data analysis and interpretation, revising
the article, and approving the final version; and Mr Haim was
responsible for preparing blinded specimens.
This trial has been registered at www.clinicaltrials.gov
(identifier NCT01575821).
www.pediatrics.org/cgi/doi/10.1542/peds.2011-3075
doi:10.1542/peds.2011-3075
Accepted for publication Apr 23, 2012
Address correspondence to Herman Avner Cohen, MD, POB 187,
Yehud 56000 Israel. E-mail: hermanc@post.tau.ac.il
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2012 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
FUNDING: This study was supported in part by a research grant
from the Israel Ambulatory Pediatric Association, Materna Infant
Nutrition Research Institute, and the Honey Board of Israel. The
funders had no role in the study design, data collection or
analysis, decision to publish, or preparation of the manuscript.
PEDIATRICS Volume 130, Number 3, September 2012 465
ARTICLE
by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
Cough is a common symptom in pedi-
atric practice. It can be particularly
troubling to children and their parents.
It often results in discomfort to the child
and loss of sleep for both the child and
parents. As a result, children miss day
care or school and parents miss a day of
work. In an attempt to treat cough,
caregivers frequently administer over-
the-counter (OTC) medications to their
children, with their attendant risks,
1–7
lack of proven efficacy,
8–11
and the dis-
approval of professional organizations
such as the American Academy of Pe-
diatrics,
12
and the Food and Drug Ad-
ministration (FDA).
13
A variety of home remedies and herbal
medications, such as licorice, cloves,
lemon, and honey, are used by some
caregivers to treat the symptoms as-
sociated with upper respiratory tract
infections (URIs).
14,15
The World Health
Organization has noted honey as a po-
tential treatment of cough and cold
symptoms, and it is considered as a de-
mulcent that is inexpensive, popular, and
safe (outside of the infant population).
14
Honey has antioxidant properties and
increases cytokine release, which may
explain its antimicrobial effects.
16–21
The objective of this trial was to com-
pare the effects on nocturnal cough and
the sleep difficulty associated with URIs
of a single nocturnal dose of 3 honey
products compared with placebo.
METHODS
Patients
Subjects were recruited from patients
who presented to 1 of 6 general pedi-
atric community clinics for an acute
care visit between January 2009 and
December 2009. Eligible patients were
those between the ages of 1 and 5 years
complaining of nocturnal cough that
was attributed to a URI. A URI was de-
fined by the presence of cough and
rhinorrhea of #7 days’duration. Other
symptoms might have included but were
not limited to nasal congestion, fever,
sore throat, myalgia, and headache.
Patients were excluded if they had signs
or symptoms of asthma, pneumonia,
laryngotracheobronchitis, sinusitis, and/
or allergic rhinitis. Patients were also
excluded if they had used any cough or
cold medication or honey on the night
before entering the study. Patients were
not excluded when analgesic medica-
tions such as acetaminophen or ibupro-
fenwereadministeredoneithernightof
the study.
Preintervention Study
Questionnaire
After attaining informed consent, all
participating parents were asked to
complete a 5-item questionnaire re-
garding their subjective assessments
of the child’s cough and sleep difficulty
on the previous night. The question-
naire used was a Hebrew version of a
previously validated questionnaire
22
(Fig 1). Survey responses were graded
on a 7-point Likert scale. Minimum
symptom severity score criteria were
established to determine which children
should enter the randomized trial. Only
children whose parents rated a severity
of at least 3 for a minimum of 2 of the 3
questions related to nocturnal cough
frequency, effect on the child’ssleep,and
effect on parental sleep on the previous
night were included.
Study Design
A double-blind randomized design was
used to conduct this study. Eligible
children were randomized to 4 treat-
ment groups: 3 groups were given1 of 3
types of honey (eucalyptus honey
(family Myrtaceae), labiatae honey
(family Labiatae ), or citrus hon ey (family
Rutaceae), or a placebo. Silan date ex-
tract was selected as the placebo be-
cause its structure, brown color, and
taste are similar to that of honey.
Intervention
The 3 honeys and the silan date extract
were prepared by the staff of the Zerifin
Breeding Apiary of the Volcani Agri-
cultural Research Center in Rechovot,
Israel. All 3 types of honey and the silan
date extract were packed in small
plastic containers of 10 g each and
marked with the letters A, B, C, or D. The
study preparations were distributed to
the pediatric community clinics in
blocks of 4. Parents were instructed to
administer 10 g of their child’s treat-
ment product within 30 minutes of the
child going to sleep. The parents were
instructed that the preparation could
be given undiluted or together with a
noncaffeinated beverage.
The parents, the physicians, and the
study coordinator did not know the
content of the preparation that was
dispensed. The envelopes containing
the codes of the study preparations
were stored at the office of the Ministry
of Agriculture, Extension Service, Bee-
keeping Department, and were not
opened until after the statistical anal-
ysis was completed.
Postintervention Study
Questionnaire
The day after the treatment, the parent
who completed the preintervention
questionnaire was contacted by tele-
phone. Trainedresearch assistants who
were blinded to the treatment group
FIGURE 1
CoughSeverity AssessmentQuestionnaire.Scoring:0 = not at all, 1 = not much, 2 = a little,3 = somewhat, 4 =
a lot, 5 = very much, 6 = extremely.
466 COHEN et al by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
asked the parent the same 5 questions
that had been answered in writing be-
fore the intervention, this time re-
garding the previous evening when the
child had received the treatment. No
physician examination was performed
on the second study day unless dictated
by illness progression.
Outcome Measures
The primary outcome was the cough
frequency. The primary outcome mea-
sure was the change in the frequency of
cough between the 2 nights. Secondary
outcome measures of importance were
changes in the cough severity, the both-
ersome nature of the cough, the effect of
the cough on sleep for both the child and
the parent, and the combined score of
these five measures.
Sample Size Analysis
On the basis of previously published
data,
8
we estimated that the sample
size necessary to detect a 0.75-point dif-
ference between any 2 treatment groups
(using analysis of variance) with 90%
power and an aof .05 was 60 subjects
per treatment group.
Tocompen sate for possible dropouts and
abnormal data distribution, we attemp-
ted to recruit 75 patients per group.
Statistical Analysis
Statistical comparisons of variables
between treatment groups were per-
formed by using the x
2
test for nominal
variables and analysis of variance for
continuous variables. For comparisons
of cough evaluation before and after
treatment, a paired Student ttest was
used. A Pvalue ,.05 was considered
statistically significant. All statistical
analyses were done by using the SPSS
package for Windows (version 15.0.1,
SPSS, Chicago, IL).
Ethics
The study was approved by the Com-
mittee for Ethics in Human Subjects
Research, Meir Medical Center, Kfar
Saba, Israel.
RESULTS
Three hundred children with URIs were
enrolled and 270 (89.7%) completed the
single-night study (Fig 2). Sixty-four
children received eucalyptus honey,
62 received citrus honey, 73 received
labiatae honey, and 71 received pla-
cebo (silan date extract). The dropout
rate was higher in the citrus and eu-
calyptus groups (P= .006).
The median age of the patients com-
pleting the study was 29 months (range
12–71 months), with no significant
difference in age among the treatment
groups (Table 1). One hundred forty-six
of the children (54%) were boys. The
participants were ill a mean 6SD of
2.8 62.0 days before enrollment, with
no significant differences among treat-
ment groups (P= .161). Almost half
(47%) of the children had .3daysof
coughing, with no difference among
groups (P= .9). In addition, there were no
significant differences between mea-
sures of symptom severity at baseline.
When symptom scores were compared
for each treatment group from the night
before treatment to the night of treat-
ment, significant differences were de-
tected in the amount of improvement
reported for all study outcome varia-
bles (Fig 3). No significant differences
were found among the different types
of honey; however, each of the honey
groups had a better response com-
pared with the silan date extract. For
cough frequency, those who received
eucalyptus honey had a mean 1.77-
point improvement compared with a
1.95-point change for those receiving
citrus honey, 1.82 change for those
receiving labiatae honey, and a 1.00
point change for those who were treated
with silan date extract (placebo group)
on the second night (F= 5.708, P,
.001). Parents also noted similar im-
provements in the severity of their
child’s cough: 1.78 points with eucalyptus
honey, 1.77 points with citrus honey, 1.94
points with labiatae honey and 0.99
points with silan date extract (F=5.78,
P,.001). Parents felt the cough also
was less bothersome on the second
night, with honey providing the greatest
relief with a 2.0-point change with euca-
lyptus honey, a 2.16-point change with
citrus honey, and a 2.07-point change
with labiatae honey, compared with
a 1.25-point change with silan date
extract group (F=4.63,P,.04). Parents
rated their children’s sleep better after
receiving honey, with improvement by
2.13 points with eucalyptus honey, 1.98
points improvement with citrus honey,
and 1.70 points with labiatae honey,
compared with a 1.21-point change
with silan date extract (F= 3.61, P,
.014). As might be expected, parental
sleep improved in a fashion similar to
that of their children, with the honey-
treatment arms improving the most,
a mean of 2.16 points with eucalyptus
honey, 2.10 points with citrus honey,
1.90 points with labiatae honey, and
1.28 points with silan date extract (F=
3.40, P,.018). When the results for
these outcomes were combined by add-
ing the scores from the individual cate-
gories, honey again proved to be the
most effective treatment. The children
improved by an average of 9.88 points
with eucalyptus honey, 10.10 points with
citrus honey, 9.51 points with labiatae
honey, compared with 5.82 points for
those treated with silan date extract (F=
5.33, P,.001).
Stomachache, nausea, or vomiting were
reported by the parents of 4 patients in
the honey treatment group (2 in the citrus,
1 in the eucalyptus, and 1 in the labiatae
honey group) and 1 in the placebo group.
The adverse events were not significantly
different between the groups.
DISCUSSION
The results of this study (Fig 3) dem-
onstrate that each of the 3 types of
ARTICLE
PEDIATRICS Volume 130, Number 3, September 2012 467
by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
honey (eucalyptus, citrus, and labiatae)
was more effective than the placebo for
the treatment of all of the outcomes
related to nocturnal cough, child sleep,
and parental sleep.
The results of our study strengthen the
observation made by Paul et al
8
that
honey products may have a beneficial
effect for symptomatic relief of noc-
turnal cough associated with URIs. Our
study differs, however, from the study of
Paul et al because they compared the
effect of 1 type of honey (buckwheat) to
dextromethorphan and a no-treatment
group, whereas our study compared
the effectiveness of 3 types honey to
placebo.
In contrast with Paul et al, we did not
document symptoms of hyperactivity,
nervousness, and insomnia in the honey
treatment groups versus the placebo
group. Shadkam et al
23
also reported
that honey had a more alleviating effect
on URI-induced cough compared with
dextromethorphan and diphenhydramine.
That study was not blinded, however.
Thus, our study further supports the
recommendations of the World Health
Organization to use honey as a poten-
tial treatment of cough.
14
Honey is a remarkably complex natural
liquid that is reported to contain at least
181 substances.
24
It has well-established
antioxidant and antimicrobial effects
FIGURE 2
Patient flow diagram.
TABLE 1 Baseline Patient Characteristics by Group
Characteristic A (n= 64) B (n= 62) C (n= 73) D (n= 71) PValue
Age in months (mean 6SD) 27.5 613.9 29 613.5 30 616.6 29 614.9 .235
Male gender
Number (%) 36 (56) 26 (36) 39 (53) 23 (32) .018
Days of illness (mean 6SD) 2.4 61.4 3.5 63.1 2.7 61.6 2.7 61.8 .16
Cough frequency score
(mean 6SD)
3.72 61.02 3.76 61.14 3.68 60.9 3.58 60.82 .73
Cough severity score (mean 6SD) 3.66 60.96 3.71 61.08 3.75 60.91 3.55 60.77 .59
Cough bother score (mean 6SD) 3.78 61.15 3.85 61.13 3.85 61.05 3.70 61.07 .84
Child sleep score (mean 6SD) 3.72 61.40 3.61 61.31 3.49 61.32 3.69 61.19 .74
Parental sleep score (mean 6SD) 3.75 61.60 3.66 61.38 3.75 61.26 3.70 61.35 .98
Combined symptom score
(mean 6SD)
18.63 65.62 18.60 65.00 18.48 64.59 18.23 64.55 .96
A, eucalyptus honey; B, citrus honey; C, labiatae honey; D, silan date extract.
468 COHEN et al by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
that have been suggested as the mech-
anism for honey’sefficacy in wound
healing and may help to explain its su-
perior results in this study.
16–21
The antioxidants present in honey come
from a variety of sources, such as vi-
tamin C, monophenolics, flavonoids,
and polyphenolics. Although there is a
wide spectrum of antioxidant types,
monophenolics such as 4-hydroxybenzoic
and 4-hydroxycinnamic acids predom-
inate in many honeys.
21,25
Most of the
antioxidant components in processed
honey are water, not lipid, soluble.
21
Different types of honey vary widely in
the quantity of water-soluble antioxi-
dants they contain.
26,27
This variability
is dependent on the honey’sfloral source,
as well as seasonal, environmental, and
other external factors. It was observed
that the darker a honey’s color, the
higher its antioxidant capacity. The
levels of certain antioxidant compo-
nents decrease with processing and
storage of honey.
21
However, available
data show that phenolic antioxidants
from processed honey are bioavailable
and increase the antioxidant activity of
plasma.
19
Eccles
26
provided another possible ex-
planation for some of the beneficial
effects of honey. Because of the close
anatomic relationship between the
sensory nerve fibers that initiate cough
and the gustatory nerve fibers that
taste sweetness, an interaction be-
tween these fibers may produce an
antitussive effect of sweet substances
via a central nervous system mecha-
nism. This theory may explain some of
the observed effect in patients treated
with silan date extract because this
is also a sweet substance. However,
the significant difference between the
honey products and the silan date ex-
tract suggests that other factors in
addition to the sweet taste of honey
contribute to its beneficial effect on
children with cough.
Silan was used as placebo in this study.
An alternative hypothesis is that silan
date extract could worsen cough and
cold symptoms. However, our data
clearly show that patients treated with
silan date extract actually improved.
There is also no reason to believe silan
caused allergic symptoms or bron-
chospasm because dates are not a
common food allergen in the Israeli
population.
27
FIGURE 3
The effect of different types of honey and silan date extract on cough frequency (I), cough severity (II), cough bothersome to child (III), the child’s sleep (IV),
parent’s sleep (V), and combined symptoms score (VI). P,.05 for the comparisons between group D and the other groups. A, eucalyptus honey; B, citrus
honey; C, labiatae honey; D, silan date extract.
ARTICLE
PEDIATRICS Volume 130, Number 3, September 2012 469
by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
Cough due to a viral URI is generally self-
limited. However, parents often wish
some active intervention. This tends to
lead to the use of OTC cough medi-
cations. However, these medications
are potentially dangerous. Many of the
adverse events reported were caused
by inadvertent overdoses when parents
gave the drug to a child too often or at
a higher than recommended dose.
Some overdoses were caused when the
parents gave a child a combination
of cold and cough medicines, not re-
alizing the product containing the same
ingredient.
Dart et al
28
reported 118 cases of fatal-
ities in children younger than 12 years
of age that were judged as possibly,
likely, or definitely related to a cough
and cold ingredient. Of these 118 cases,
103 involved a nonprescription medica-
tion, and the ingredients most often
mentioned were pseudoephedrine (n=
45), diphenhydramine (n=38),and
dextromethorphan (n= 36). Of these
cases, the evidence indicated that 88
involved an overdose. Several contrib-
uting factors were identified, age ,2
years, use of medication for sedation,
use in day-care settings, use of 2
medicines with the same ingredient,
failure to use a measuring device,
product misidentification, and use of
a nonprescription product intended
for adult use.
Rimsza et al reported 10 unexpected
deaths that were associated with the
use of OTC cough and cold medications
in a 1-year period.
29
The authors rec-
ommended that such medications
should not be given to infants because
they may present a serious health
hazard, and there is no evidence to
support the efficacy and safe dosage of
these medications in infants. Rimsza
et al also suggest that educational
campaigns to decrease the use of OTC
cough and cold medications in infants
need to be increased.
29
Lokker et al reported that unintentional
misuse of OTC cold products is common
and could result in harm if medications
are given inappropriately. Label lan-
guage and graphics seem to influence
inappropriate interpretation of OTC
product age indications.
30
As a result of
these studies, an FDA advisory com-
mittee recommended against the use
of OTC cough and cold medications in
children aged ,6 years, and a sub-
sequent FDA public health advisory was
issued recommending against the use
of these medications in children ,2
years of age.
13
Honey is an alternative that is generally
regarded as safe for children older
than 1 year. Allan et al
31
stated that
evidence for honey in acute pediatric
cough supports a small effect, but
clinical significance is uncertain. Our
randomized, placebo-controlled study
seems to indicate that treatment with
honey can be clinically effective.
We suggest, in concordance with the
FDA
13
and the Israeli Ministry of Health
Pharmaceutical Administration, that
caregivers and clinicians should be
aware of the risk of serious adverse
events from administering cough and
cold medications to children ,2 years
of age and use several precautions
when using them in older children (2–
11 years). We believe that educational
campaigns to decrease the use of OTC
cough and cold medications in children
need to be increased. On the basis of
our findings, honey can be offered as
an alternate treatment to children .1
year of age. Honey should not be given
to children ,1 year of age because of
the risk of infantile botulism.
32
Because
frequent use of honey can cause dental
caries, the recommendation should be
for a short course of honey.
The study is limited by the subjective
nature of the survey used. However,
clinicians and parents often make de-
cisions based on subjective assess-
ments of symptom severity. It should
also be noted that it is possible that
some of the improvement measured
could also be attributed to the nat-
ural history of URIs, which generally
improve with time and supportive
care.Furthermore,compliancewith
honey and placebo administration
could not be guaranteed. However,
every parent reported that their child
took the treatment as recommended.
Another limitation is the fact that the
effect of only a single dose was
evaluated. If the intervention period
would have been longer and more
than 1 dose given, the results would
have been more reliable and more
valuable.
The dropout rate was higher for chil-
dren receiving citrus and eucalyptus
honey. The exact reason for the higher
dropout rate in these groups is not
known. Because these types of honey
are more aromatic, it is possible that
some children disliked the honey
taste.
CONCLUSIONS
Parents rated each of the honey prod-
ucts more favorably than the silan
date extract for symptomatic relief of
their children’s nocturnal cough and
sleep difficulty due to URI. Honey may
be a preferable treatment of cough
and sleep difficulties associated with
childhood URI. In light of this study,
honey can be considered an effective
and safe treatment of children .1 year
of age.
ACKNOWLEDGMENT
We thank Dorit Krash of Clalit Health
Services for statistical analysis.
470 COHEN et al by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
REFERENCES
1. Kuehn BM. FDA: cold medications risky for
young children. JAMA. 2007;298(10):1151
2. Warden CR, Diekema DS, Robertson WO.
Dystonic reaction associated with dextro-
methorphan ingestion in a toddler. Pediatr
Emerg Care. 1997;13(3):214–215
3. Centers for Disease Control and Prevention
(CDC). Infant deaths associated with cough
andcoldmedications—two states, 2005.
MMWR Morb Mortal Wkly Rep. 2007;56(1):1–4
4. Gun VL, Taha SH, Liebelt EL, Serwint JR.
Toxicity of over-the-counter cough and cold
medications. Pediatrics. 2001;108(3). Avail-
able at: www.pediatrics.org/cgi/content/full/
108/3/e52
5. Watson WA, Litovitz TL, Rodgers GC Jr, et al.
2004 Annual report of the American Asso-
ciation of Poison Control Centers Toxic Ex-
posure Surveillance System. Am J Emerg
Med. 2005;23(5):589–666
6. Marinetti L, Lehman L, Casto B, Harshbarger
K, Kubiczek P, Davis J. Over-the-counter cold
medications—postmortem findings in in-
fants and the relationship to cause of death.
J Anal Toxicol. 2005;29(7):738–743
7. Pen de r ES , Parks BR . Tox ic it y with
dextromethorphan-containing preparations:
a literature review and report of two addi-
tional cases. Pediatr Emerg Care. 1991;7(3):
163–165
8. Paul IM, Beiler J, McMonagle A, Shaffer ML,
Duda L, Berlin CM Jr. Effect of honey dex-
tromethorphan, and no treatment on noc-
turnal cough and sleep quality for coughing
children and their parents. Arch Pediatr
Adolesc Med. 2007;161(12):1140–1146
9. Paul IM, Yoder KE, Crowell KR, et al. Effect of
dextromethorphan, diphenhydramine, and
placebo on nocturnal cough and sleep quality
for coughing children and their parents.
Pediatrics. 2004;114(1). Available at: www.
pediatrics.org/cgi/content/full/114/1/e85
10. Warren MD, Pont SJ, Barkin SL, et al. The
effect of honey on nocturnal cough and
sleep quality for children and their parents.
Arch Pediatr Adolesc Med. 2007;161(12):
1149–1153
11. Yoder KE, Shaffer ML, La Tournous SJ, Paul
IM. Child assessment of dextromethorphan,
diphenhydramine, and placebo for noc-
turnal cough due to upper respiratory
infection. Clin Pediatr (Phila). 2006;45(7):
633–640
12. American Academy of Pediatrics, Committee on
Drugs. Use of codeine- and dextromethorphan-
containing cough remedies in children. Pe-
diatrics. 1997;99(6):918–920
13. Food and Drug Administration. FDA releases
recommendati ons re gard ing use of over-
the-counter cough and cold products.
January 17, 2008. Available at: www.fda.
gov/bbs/topics/NEWS/2008/NEW01778.html.
Accessed May 12, 2011
14. Department of Child and Adolescent Health.
Cough and cold remedies for the treatment
of acute respiratory infections in young
children. Geneva, Switzerland: World Health
Organization 2001
15. Ziment I. Herbal antitussives. Pulm Phar-
macol Ther. 2002;15(3):327–333
16. Wahdan HA. Causes of the antimicrobial
activity of honey. Infection. 1998;26(1):26–31
17. Lusby PE, Coombes AL, Wilkinson JM. Bac-
tericidal activity of different honeys against
pathogenic bacteria. Arch Med Res. 2005;36
(5):464–467
18. Adeleye IA, Opiah L. Antimicrobial activity of
extracts of local cough mixtures on upper
respiratory tract bacterial pathogens. West
Indian Med J. 2003;52(3):188–190
19. Schramm DD, Karim M, Schrader HR, Holt
RR, Cardetti M, Keen CL. Honey with high
levels of antioxidants can provide pro-
tection to healthy human subjects. J Agric
Food Chem. 2003;51(6):1732–1735
20. Tonks AJ, Cooper RA, Jones KP, Blair S,
Parton J, Tonks A. Honey stimulates inflam-
matory cytokine production from monocytes.
Cytokine. 2003;21(5):242–247
21. Gheldof N, Wang XH, Engeseth NJ. Identifi-
cation and quantification of antioxidant
components of honeys from various floral
sources. J Agric Food Chem. 2002;50(21):
5870–5877
22. Hartnick CJ, Zurakowski D, Haver K. Vali-
dation of a pediatric cough questionnaire.
Ear Nose Throat J. 2009;88(11):1213–1217
23. Shadkam MN, Mozffari-Khosravi H, Moyazan
MR. A comparison of the effect of honey,
dextromethorphan, and diphenhydramine
on nightly cough and sleep quality in chil-
dren and their parents. J Altern Comple-
ment Med. 2010;6(7):787–793
24. White JW. Composition of honey. In Crabe E,
ed. Honey: A Comprehensive Survey. New
York, NY: Crane, Russak Company; 1975;
157–206
25. Gheldof N, Engeseth NJ. Antioxidant capac-
ity of honeys from various floral sources
based on the determination of oxygen
radical absorbance capacity and inhibition
of in vitro lipoprotein oxidation in human
serum samples. J Agric Food Chem. 2002;
50(10):3050–3055
26. Eccles R. Mechanisms of the placebo effect
of sweet cough syrups. Respir Physiol
Neurobiol. 2006;152(3):340–348
27. Kornizky Y, Topilsky M, Fireman E, Kivity
S, Kivity S. Specific IgE antibodies to aer-
oallergens and food among Israelis. Ann
Allergy Asthma Immunol. 1999;83(2):149–
152
28. Dart RC, Paul IM, Bond GR, et al. Pediatric
fatalities associated with over the counter
(nonprescription) cough and cold medi-
cations. Ann Emerg Med. 2009;53(4):411–
417
29. Rimsza ME, Newberry S. Unexpected infant
deaths associated with use of cough and
cold medications. Pediatrics. 2008;122(2).
Available at: www.pediatrics.org/cgi/content/
full/122/2/e318
30. Lokker N, Sanders L, Perrin EM, et al. Pa-
rental misinterpretations of over-the-counter
pediatric cough and cold medication labels.
Pediatrics . 2009;123(6):1464–1471
31. Allan GM, Korownyk C, Kolber M. Do cough
suppressants or honey help pediatric cough?
Can Fam Physician. 2011;57(4):435
32. Cox N, Hinkle R. Infant botulism. Am Fam
Physician. 2002;65(7):1388–1392
ARTICLE
PEDIATRICS Volume 130, Number 3, September 2012 471
by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
DOI: 10.1542/peds.2011-3075
; originally published online August 6, 2012; 2012;130;465Pediatrics
Yosef Uziel, Eran Kozer, Avishalom Pomeranz and Haim Efrat
Herman Avner Cohen, Josef Rozen, Haim Kristal, Yoseph Laks, Mati Berkovitch,
Randomized, Placebo-Controlled Study
Effect of Honey on Nocturnal Cough and Sleep Quality: A Double-blind,
Services
Updated Information &
ml
http://pediatrics.aappublications.org/content/130/3/465.full.ht
including high resolution figures, can be found at:
References
ml#ref-list-1
http://pediatrics.aappublications.org/content/130/3/465.full.ht
at:
This article cites 28 articles, 7 of which can be accessed free
Citations
ml#related-urls
http://pediatrics.aappublications.org/content/130/3/465.full.ht
This article has been cited by 6 HighWire-hosted articles:
Subspecialty Collections
_tract_sub
http://pediatrics.aappublications.org/cgi/collection/respiratory
Respiratory Tract
the following collection(s):
This article, along with others on similar topics, appears in
Permissions & Licensing
tml
http://pediatrics.aappublications.org/site/misc/Permissions.xh
tables) or in its entirety can be found online at:
Information about reproducing this article in parts (figures,
Reprints http://pediatrics.aappublications.org/site/misc/reprints.xhtml
Information about ordering reprints can be found online:
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Grove Village, Illinois, 60007. Copyright © 2012 by the American Academy of Pediatrics. All
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
DOI: 10.1542/peds.2011-3075
; originally published online August 6, 2012; 2012;130;465Pediatrics
Yosef Uziel, Eran Kozer, Avishalom Pomeranz and Haim Efrat
Herman Avner Cohen, Josef Rozen, Haim Kristal, Yoseph Laks, Mati Berkovitch,
Randomized, Placebo-Controlled Study
Effect of Honey on Nocturnal Cough and Sleep Quality: A Double-blind,
http://pediatrics.aappublications.org/content/130/3/465.full.html
located on the World Wide Web at:
The online version of this article, along with updated information and services, is
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2012 by the American Academy
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
publication, it has been published continuously since 1948. PEDIATRICS is owned,
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
by guest on October 21, 2015pediatrics.aappublications.orgDownloaded from
