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 asa cough medication by the World Health Organization. To date, theefficacy of this treatment has been shown in 2 studies: one testedonly buckwheat honey and the other study was not blinded.

WHAT THIS STUDY ADDS: In a randomized controlled trial, wecompared 3 types of honey versus placebo as a treatment ofupper respiratory tract infection–associated cough. These typesof honey were superior to placebo in alleviating cough.

abstractOBJECTIVES: To compare the effects of a single nocturnal dose of 3honey products (eucalyptus honey, citrus honey, or labiatae honey) toplacebo (silan date extract) on nocturnal cough and difficulty sleepingassociated with childhood upper respiratory tract infections (URIs).

METHODS: A survey was administered to parents on 2 consecutivedays, first on the day of presentation, when no medication had beengiven the previous evening, and the following day, when the study prep-aration was given before bedtime, based on a double-blind randomizationplan. Participants included 300 children aged 1 to 5 years with URIs,nocturnal cough, and illness duration of #7 days from 6 generalpediatric community clinics. Eligible children received a single dose of10 g of eucalyptus honey, citrus honey, labiatae honey, or placeboadministered 30 minutes before bedtime. Main outcome measureswere 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 wasa significant improvement from the night before treatment to the nightof treatment. However, the improvement was greater in the honeygroups for all the main outcome measures.

CONCLUSIONS: Parents rated the honey products higher than the silandate extract for symptomatic relief of their children’s nocturnal coughand sleep difficulty due to URI. Honey may be a preferable treatmentfor cough and sleep difficulty associated with childhood URI. Pediatrics2012;130:1–7

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 Yosef Uziel, MD,b,g Eran Kozer, MD,b,h AvishalomPomeranz, MD,b,i and Haim Efratj

aPediatric Ambulatory Community Clinic, Petach Tikva, Israel;bSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;cPediatric Ambulatory Community Clinic, Kefar Saba, Israel;dPediatric Ambulatory Community Clinic, Kiryat Shmone, Israel;ePediatric Ambulatory Community Clinic, Ramat Aviv, Israel;fClinical Pharmacology Unit, Assaf Harofeh Medical Center,Zerifin, Israel; gDepartment of Pediatrics, Meir Medical Center,Kfar Saba, Israel; hPediatric Emergency Unit, Assaf HarofehMedical Center, Zerifin, Israel; iDepartment of Pediatrics, MeirMedical Center, Kfar Saba, Israel; and jZerifin Breeding Apiary,Volcani Agricultural Research Center, Rechovot, Israel

KEY WORDScough, children, honey

ABBREVIATIONSFDA—Food and Drug AdministrationOTC—over-the-counterURI—upper respiratory tract infection

†Deceased.

Dr Cohen was responsible for conception and design of study,data acquisition, analysis and interpretation of data, and hedrafted and revised the article and approved the final version;Dr Rozen was responsible for data acquisition, data analysis andinterpretation, and critical revision of the article; Drs Kristal,Laks, Berkovitch, Uziel, Kozer, and Pomeranz were responsiblefor data acquisition, data analysis and interpretation, revisingthe article, and approving the final version; and Mr Haim wasresponsible 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 haveno financial relationships relevant to this article to disclose.

FUNDING: This study was supported in part by a research grantfrom the Israel Ambulatory Pediatric Association, Materna InfantNutrition Research Institute, and the Honey Board of Israel. Thefunders had no role in the study design, data collection oranalysis, decision to publish, or preparation of the manuscript.

PEDIATRICS Volume 130, Number 3, September 2012 1

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Cough is a common symptom in pedi-atric practice. It can be particularlytroubling to children and their parents.It often results in discomfort to the childand loss of sleep for both the child andparents. As a result, children miss daycareorschool andparentsmissadayofwork. In an attempt to treat cough,caregivers frequently administer over-the-counter (OTC) medications to theirchildren, with their attendant risks,1–7

lack of proven efficacy,8–11 and the dis-approval of professional organizationssuch as the American Academy of Pe-diatrics,12 and the Food and Drug Ad-ministration (FDA).13

A variety of home remedies and herbalmedications, such as licorice, cloves,lemon, and honey, are used by somecaregivers to treat the symptoms as-sociated with upper respiratory tractinfections (URIs).14,15 The World HealthOrganization has noted honey as a po-tential treatment of cough and coldsymptoms, and it is considered as a de-mulcent that is inexpensive, popular, andsafe (outside of the infant population).14

Honey has antioxidant properties andincreases cytokine release, which mayexplain its antimicrobial effects.16–21

The objective of this trial was to com-pare the effects onnocturnal coughandthe sleep difficulty associated with URIsof a single nocturnal dose of 3 honeyproducts compared with placebo.

METHODS

Patients

Subjects were recruited from patientswho presented to 1 of 6 general pedi-atric community clinics for an acutecare visit between January 2009 andDecember 2009. Eligible patients werethose between the ages of 1 and 5 yearscomplaining of nocturnal cough thatwas attributed to a URI. A URI was de-fined by the presence of cough andrhinorrhea of#7 days’duration. Othersymptomsmight have included but werenot limited to nasal congestion, fever,

sore throat, myalgia, and headache.Patients were excluded if they had signsor symptoms of asthma, pneumonia,laryngotracheobronchitis, sinusitis, and/or allergic rhinitis. Patients were alsoexcluded if they had used any cough orcold medication or honey on the nightbefore entering the study. Patients werenot excluded when analgesic medica-tions such as acetaminophen or ibupro-fen were administered on either night ofthe study.

Preintervention StudyQuestionnaire

After attaining informed consent, allparticipating parents were asked tocomplete a 5-item questionnaire re-garding their subjective assessmentsof the child’s cough and sleep difficultyon the previous night. The question-naire used was a Hebrew version of apreviously validated questionnaire22

(Fig 1). Survey responses were gradedon a 7-point Likert scale. Minimumsymptom severity score criteria wereestablished to determinewhich childrenshould enter the randomized trial. Onlychildren whose parents rated a severityof at least 3 for a minimum of 2 of the 3questions related to nocturnal coughfrequency, effect on the child’s sleep, andeffect on parental sleep on the previousnight were included.

Study Design

A double-blind randomized design wasused to conduct this study. Eligiblechildren were randomized to 4 treat-ment groups: 3 groupswere given 1 of 3types of honey (eucalyptus honey(family Myrtaceae), labiatae honey

(family Labiatae), or citrushoney (familyRutaceae), or a placebo. Silan date ex-tract was selected as the placebo be-cause its structure, brown color, andtaste are similar to that of honey.

Intervention

The 3 honeys and the silan date extractwere prepared by the staff of the ZerifinBreeding Apiary of the Volcani Agri-cultural Research Center in Rechovot,Israel. All 3 types of honey and the silandate extract were packed in smallplastic containers of 10 g each andmarkedwith the letters A, B, C, or D. Thestudy preparations were distributed tothe pediatric community clinics inblocks of 4. Parents were instructed toadminister 10 g of their child’s treat-ment product within 30 minutes of thechild going to sleep. The parents wereinstructed that the preparation couldbe given undiluted or together with anoncaffeinated beverage.

The parents, the physicians, and thestudy coordinator did not know thecontent of the preparation that wasdispensed. The envelopes containingthe codes of the study preparationswere stored at the office of the Ministryof Agriculture, Extension Service, Bee-keeping Department, and were notopened until after the statistical anal-ysis was completed.

Postintervention StudyQuestionnaire

The day after the treatment, the parentwho completed the preinterventionquestionnaire was contacted by tele-phone. Trainedresearchassistantswhowere blinded to the treatment group

FIGURE 1CoughSeverityAssessmentQuestionnaire.Scoring:0=notatall, 1=notmuch,2=a little, 3=somewhat, 4=a lot, 5 = very much, 6 = extremely.

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asked the parent the same 5 questionsthat had been answered in writing be-fore the intervention, this time re-garding the previous evening when thechild had received the treatment. Nophysician examination was performedon the second study day unless dictatedby illness progression.

Outcome Measures

The primary outcome was the coughfrequency. The primary outcome mea-surewas the change in the frequency ofcough between the 2 nights. Secondaryoutcomemeasures of importancewerechanges in the cough severity, the both-ersome nature of the cough, the effect ofthe cough on sleep for both the child andthe parent, and the combined score ofthese five measures.

Sample Size Analysis

On the basis of previously publisheddata,8 we estimated that the samplesize necessary to detect a 0.75-point dif-ference between any 2 treatment groups(using analysis of variance) with 90%power and an a of .05 was 60 subjectsper treatment group.

Tocompensate forpossibledropoutsandabnormal data distribution, we attemp-ted to recruit 75 patients per group.

Statistical Analysis

Statistical comparisons of variablesbetween treatment groups were per-formed by using the x2 test for nominalvariables and analysis of variance forcontinuous variables. For comparisonsof cough evaluation before and aftertreatment, a paired Student t test wasused. A P value ,.05 was consideredstatistically significant. All statisticalanalyses were done by using the SPSSpackage 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, KfarSaba, Israel.

RESULTS

Three hundred children with URIs wereenrolled and 270 (89.7%) completed thesingle-night study (Fig 2). Sixty-fourchildren received eucalyptus honey,62 received citrus honey, 73 receivedlabiatae honey, and 71 received pla-cebo (silan date extract). The dropoutrate was higher in the citrus and eu-calyptus groups (P = .006).

The median age of the patients com-pleting the study was 29months (range12–71 months), with no significantdifference in age among the treatmentgroups (Table 1). One hundred forty-sixof the children (54%) were boys. Theparticipants were ill a mean 6 SD of2.8 6 2.0 days before enrollment, withno significant differences among treat-ment groups (P = .161). Almost half(47%) of the children had .3 days ofcoughing, with no difference amonggroups (P= .9). In addition, therewere nosignificant differences between mea-sures of symptom severity at baseline.

When symptom scores were comparedforeach treatmentgroup fromthenightbefore treatment to the night of treat-ment, significant differences were de-tected in the amount of improvementreported for all study outcome varia-bles (Fig 3). No significant differenceswere found among the different typesof honey; however, each of the honeygroups had a better response com-pared with the silan date extract. Forcough frequency, those who receivedeucalyptus honey had a mean 1.77-point improvement compared with a1.95-point change for those receivingcitrus honey, 1.82 change for thosereceiving labiatae honey, and a 1.00point change for thosewhowere treatedwith 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 eucalyptushoney, 1.77 points with citrus honey, 1.94points with labiatae honey and 0.99points with silan date extract (F = 5.78,P , .001). Parents felt the cough alsowas less bothersome on the secondnight, with honey providing the greatestrelief with a 2.0-point change with euca-lyptus honey, a 2.16-point change withcitrus honey, and a 2.07-point changewith labiatae honey, compared witha 1.25-point change with silan dateextract group (F = 4.63, P, .04). Parentsrated their children’s sleep better afterreceiving honey, with improvement by2.13 points with eucalyptus honey, 1.98points improvement with citrus honey,and 1.70 points with labiatae honey,compared with a 1.21-point changewith silan date extract (F = 3.61, P ,.014). As might be expected, parentalsleep improved in a fashion similar tothat of their children, with the honey-treatment arms improving the most,a mean of 2.16 points with eucalyptushoney, 2.10 points with citrus honey,1.90 points with labiatae honey, and1.28 points with silan date extract (F =3.40, P , .018). When the results forthese outcomes were combined by add-ing the scores from the individual cate-gories, honey again proved to be themost effective treatment. The childrenimproved by an average of 9.88 pointswith eucalyptus honey, 10.10 points withcitrus honey, 9.51 points with labiataehoney, compared with 5.82 points forthose treated with silan date extract (F =5.33, P, .001).

Stomachache, nausea, or vomiting werereported by the parents of 4 patients inthehoneytreatmentgroup(2inthecitrus,1 in the eucalyptus, and 1 in the labiataehoney group) and 1 in the placebo group.The adverse eventswere not significantlydifferent between the groups.

DISCUSSION

The results of this study (Fig 3) dem-onstrate that each of the 3 types of

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honey (eucalyptus, citrus, and labiatae)was more effective than the placebo forthe treatment of all of the outcomesrelated to nocturnal cough, child sleep,and parental sleep.

The results of our study strengthen theobservation made by Paul et al8 that

honey products may have a beneficialeffect for symptomatic relief of noc-turnal cough associated with URIs. Ourstudy differs, however, from the study ofPaul et al because they compared theeffect of 1 type of honey (buckwheat) todextromethorphan and a no-treatment

group, whereas our study comparedthe effectiveness of 3 types honey toplacebo.

In contrast with Paul et al, we did notdocument symptoms of hyperactivity,nervousness,and insomnia in thehoneytreatment groups versus the placebogroup. Shadkam et al23 also reportedthat honey had amore alleviating effecton URI-induced cough compared withdextromethorphan and diphenhydramine.That study was not blinded, however.Thus, our study further supports therecommendations of the World HealthOrganization to use honey as a poten-tial treatment of cough.14

Honey is a remarkably complex naturalliquid that is reported to contain at least181 substances.24 It haswell-establishedantioxidant and antimicrobial effects

FIGURE 2Patient flow diagram.

TABLE 1 Baseline Patient Characteristics by Group

Characteristic A (n = 64) B (n = 62) C (n = 73) D (n = 71) P Value

Age in months (mean 6 SD) 27.5 6 13.9 29 6 13.5 30 6 16.6 29 6 14.9 .235Male genderNumber (%) 36 (56) 26 (36) 39 (53) 23 (32) .018Days of illness (mean 6 SD) 2.4 6 1.4 3.5 6 3.1 2.7 6 1.6 2.7 6 1.8 .16Cough frequency score(mean 6 SD)

3.72 6 1.02 3.76 6 1.14 3.68 6 0.9 3.58 6 0.82 .73

Cough severity score (mean 6 SD) 3.66 6 0.96 3.71 6 1.08 3.75 6 0.91 3.55 6 0.77 .59Cough bother score (mean 6 SD) 3.78 6 1.15 3.85 6 1.13 3.85 6 1.05 3.70 6 1.07 .84Child sleep score (mean6 SD) 3.72 6 1.40 3.61 6 1.31 3.49 6 1.32 3.69 6 1.19 .74Parental sleep score (mean6 SD) 3.75 6 1.60 3.66 6 1.38 3.75 6 1.26 3.70 6 1.35 .98Combined symptom score(mean 6 SD)

18.63 6 5.62 18.60 6 5.00 18.48 6 4.59 18.23 6 4.55 .96

A, eucalyptus honey; B, citrus honey; C, labiatae honey; D, silan date extract.

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that have been suggested as the mech-anism for honey’s efficacy in woundhealing and may help to explain its su-perior results in this study.16–21

The antioxidants present in honey comefrom a variety of sources, such as vi-tamin C, monophenolics, flavonoids,and polyphenolics. Although there is awide spectrum of antioxidant types,monophenolicssuchas4-hydroxybenzoicand 4-hydroxycinnamic acids predom-inate in many honeys.21,25 Most of theantioxidant components in processedhoney are water, not lipid, soluble.21

Different types of honey vary widely inthe quantity of water-soluble antioxi-dants they contain.26,27 This variabilityis dependent on the honey’s floral source,as well as seasonal, environmental, andother external factors. It was observed

that the darker a honey’s color, thehigher its antioxidant capacity. Thelevels of certain antioxidant compo-nents decrease with processing andstorage of honey.21 However, availabledata show that phenolic antioxidantsfrom processed honey are bioavailableand increase the antioxidant activity ofplasma.19

Eccles26 provided another possible ex-planation for some of the beneficialeffects of honey. Because of the closeanatomic relationship between thesensory nerve fibers that initiate coughand the gustatory nerve fibers thattaste sweetness, an interaction be-tween these fibers may produce anantitussive effect of sweet substancesvia a central nervous system mecha-nism. This theory may explain some of

the observed effect in patients treatedwith silan date extract because thisis also a sweet substance. However,the significant difference between thehoney products and the silan date ex-tract suggests that other factors inaddition to the sweet taste of honeycontribute to its beneficial effect onchildren with cough.

Silan was used as placebo in this study.An alternative hypothesis is that silandate extract could worsen cough andcold symptoms. However, our dataclearly show that patients treated withsilan date extract actually improved.There is also no reason to believe silancaused allergic symptoms or bron-chospasm because dates are not acommon food allergen in the Israelipopulation.27

FIGURE 3The 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, citrushoney; C, labiatae honey; D, silan date extract.

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Coughdue toaviral URI is generally self-limited. However, parents often wishsome active intervention. This tends tolead to the use of OTC cough medi-cations. However, these medicationsare potentially dangerous. Many of theadverse events reported were causedby inadvertent overdoseswhenparentsgave the drug to a child too often or ata higher than recommended dose.Some overdoseswere caused when theparents gave a child a combinationof cold and cough medicines, not re-alizing the product containing the sameingredient.

Dart et al28 reported 118 cases of fatal-ities in children younger than 12 yearsof age that were judged as possibly,likely, or definitely related to a coughand cold ingredient. Of these 118 cases,103 involved a nonprescription medica-tion, and the ingredients most oftenmentioned were pseudoephedrine (n =45), diphenhydramine (n = 38), anddextromethorphan (n = 36). Of thesecases, the evidence indicated that 88involved an overdose. Several contrib-uting factors were identified, age ,2years, use of medication for sedation,use in day-care settings, use of 2medicines with the same ingredient,failure to use a measuring device,product misidentification, and use ofa nonprescription product intendedfor adult use.

Rimsza et al reported 10 unexpecteddeaths that were associated with theuse of OTC cough and cold medicationsin a 1-year period.29 The authors rec-ommended that such medicationsshould not be given to infants becausethey may present a serious healthhazard, and there is no evidence tosupport the efficacy and safe dosage ofthese medications in infants. Rimszaet al also suggest that educationalcampaigns to decrease the use of OTC

cough and cold medications in infantsneed to be increased.29

Lokker et al reported that unintentionalmisuse of OTC cold products is commonand could result in harm if medicationsare given inappropriately. Label lan-guage and graphics seem to influenceinappropriate interpretation of OTCproduct age indications.30 As a result ofthese studies, an FDA advisory com-mittee recommended against the useof OTC cough and cold medications inchildren aged ,6 years, and a sub-sequent FDA public health advisory wasissued recommending against the useof these medications in children ,2years of age.13

Honey is analternative that is generallyregarded as safe for children olderthan 1 year. Allan et al31 stated thatevidence for honey in acute pediatriccough supports a small effect, butclinical significance is uncertain. Ourrandomized, placebo-controlled studyseems to indicate that treatment withhoney can be clinically effective.

We suggest, in concordance with theFDA13 and the Israeli Ministry of HealthPharmaceutical Administration, thatcaregivers and clinicians should beaware of the risk of serious adverseevents from administering cough andcold medications to children,2 yearsof age and use several precautionswhen using them in older children (2–11 years). We believe that educationalcampaigns to decrease the use of OTCcough and coldmedications in childrenneed to be increased. On the basis ofour findings, honey can be offered asan alternate treatment to children .1year of age. Honey should not be givento children ,1 year of age because ofthe risk of infantile botulism.32 Becausefrequent use of honey can cause dentalcaries, the recommendation should befor a short course of honey.

The study is limited by the subjectivenature of the survey used. However,clinicians and parents often make de-cisions based on subjective assess-ments of symptom severity. It shouldalso be noted that it is possible thatsome of the improvement measuredcould also be attributed to the nat-ural history of URIs, which generallyimprove with time and supportivecare. Furthermore, compliance withhoney and placebo administrationcould not be guaranteed. However,every parent reported that their childtook the treatment as recommended.Another limitation is the fact that theeffect of only a single dose wasevaluated. If the intervention periodwould have been longer and morethan 1 dose given, the results wouldhave been more reliable and morevaluable.

The dropout rate was higher for chil-dren receiving citrus and eucalyptushoney. The exact reason for the higherdropout rate in these groups is notknown. Because these types of honeyare more aromatic, it is possible thatsome children disliked the honeytaste.

CONCLUSIONS

Parents rated each of the honey prod-ucts more favorably than the silandate extract for symptomatic relief oftheir children’s nocturnal cough andsleep difficulty due to URI. Honey maybe a preferable treatment of coughand sleep difficulties associated withchildhood URI. In light of this study,honey can be considered an effectiveand safe treatment of children.1 yearof age.

ACKNOWLEDGMENTWe thank Dorit Krash of Clalit HealthServices for statistical analysis.

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REFERENCES

1. Kuehn BM. FDA: cold medications risky foryoung children. JAMA. 2007;298(10):1151

2. Warden CR, Diekema DS, Robertson WO.Dystonic reaction associated with dextro-methorphan ingestion in a toddler. PediatrEmerg Care. 1997;13(3):214–215

3. Centers for Disease Control and Prevention(CDC). Infant deaths associated with coughand cold medications—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 coldmedications. 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 EmergMed. 2005;23(5):589–666

6. Marinetti L, Lehman L, Casto B, HarshbargerK, Kubiczek P, Davis J. Over-the-counter coldmedications—postmortem findings in in-fants and the relationship to cause of death.J Anal Toxicol. 2005;29(7):738–743

7. Pender ES, Parks BR. Toxicity withdextromethorphan-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 coughingchildren and their parents. Arch PediatrAdolesc Med. 2007;161(12):1140–1146

9. Paul IM, Yoder KE, Crowell KR, et al. Effect ofdextromethorphan, diphenhydramine, andplacebo on nocturnal cough and sleep qualityfor 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. Theeffect of honey on nocturnal cough andsleep quality for children and their parents.Arch Pediatr Adolesc Med. 2007;161(12):1149–1153

11. Yoder KE, Shaffer ML, La Tournous SJ, PaulIM. Child assessment of dextromethorphan,diphenhydramine, and placebo for noc-turnal cough due to upper respiratoryinfection. Clin Pediatr (Phila). 2006;45(7):633–640

12. American Academy of Pediatrics, Committee onDrugs. Use of codeine- and dextromethorphan-containing cough remedies in children. Pe-diatrics. 1997;99(6):918–920

13. Food and Drug Administration. FDA releasesrecommendations regarding 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 treatmentof acute respiratory infections in youngchildren. Geneva, Switzerland: World HealthOrganization 2001

15. Ziment I. Herbal antitussives. Pulm Phar-macol Ther. 2002;15(3):327–333

16. Wahdan HA. Causes of the antimicrobialactivity of honey. Infection. 1998;26(1):26–31

17. Lusby PE, Coombes AL, Wilkinson JM. Bac-tericidal activity of different honeys againstpathogenic bacteria. Arch Med Res. 2005;36(5):464–467

18. Adeleye IA, Opiah L. Antimicrobial activity ofextracts of local cough mixtures on upperrespiratory tract bacterial pathogens. WestIndian Med J. 2003;52(3):188–190

19. Schramm DD, Karim M, Schrader HR, HoltRR, Cardetti M, Keen CL. Honey with highlevels of antioxidants can provide pro-tection to healthy human subjects. J AgricFood 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 antioxidantcomponents of honeys from various floralsources. 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, MoyazanMR. A comparison of the effect of honey,dextromethorphan, and diphenhydramineon 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. NewYork, NY: Crane, Russak Company; 1975;157–206

25. Gheldof N, Engeseth NJ. Antioxidant capac-ity of honeys from various floral sourcesbased on the determination of oxygenradical absorbance capacity and inhibitionof in vitro lipoprotein oxidation in humanserum samples. J Agric Food Chem. 2002;50(10):3050–3055

26. Eccles R. Mechanisms of the placebo effectof sweet cough syrups. Respir PhysiolNeurobiol. 2006;152(3):340–348

27. Kornizky Y, Topilsky M, Fireman E, KivityS, Kivity S. Specific IgE antibodies to aer-oallergens and food among Israelis. AnnAllergy Asthma Immunol. 1999;83(2):149–152

28. Dart RC, Paul IM, Bond GR, et al. Pediatricfatalities 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 infantdeaths associated with use of cough andcold 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-counterpediatric cough and cold medication labels.Pediatrics. 2009;123(6):1464–1471

31. Allan GM, Korownyk C, Kolber M. Do coughsuppressants or honey help pediatric cough?Can Fam Physician. 2011;57(4):435

32. Cox N, Hinkle R. Infant botulism. Am FamPhysician. 2002;65(7):1388–1392

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originally published online August 6, 2012; Pediatrics 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,

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