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2 COHEN et al
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asked the parent the same 5 questions Research, Meir Medical Center, Kfar child’s cough: 1.78 points with eucalyptus
that had been answered in writing be- Saba, Israel. honey, 1.77 points with citrus honey, 1.94
fore the intervention, this time re- points with labiatae honey and 0.99
garding the previous evening when the RESULTS points with silan date extract (F = 5.78,
child had received the treatment. No P , .001). Parents felt the cough also
Three hundred children with URIs were
physician examination was performed was less bothersome on the second
enrolled and 270 (89.7%) completed the
on the second study day unless dictated night, with honey providing the greatest
single-night study (Fig 2). Sixty-four
by illness progression. relief with a 2.0-point change with euca-
children received eucalyptus honey,
lyptus honey, a 2.16-point change with
62 received citrus honey, 73 received
Outcome Measures citrus honey, and a 2.07-point change
labiatae honey, and 71 received pla-
The primary outcome was the cough with labiatae honey, compared with
cebo (silan date extract). The dropout
frequency. The primary outcome mea- a 1.25-point change with silan date
rate was higher in the citrus and eu-
sure was the change in the frequency of extract group (F = 4.63, P , .04). Parents
calyptus groups (P = .006).
cough between the 2 nights. Secondary rated their children’s sleep better after
The median age of the patients com- receiving honey, with improvement by
outcome measures of importance were
pleting the study was 29 months (range 2.13 points with eucalyptus honey, 1.98
changes in the cough severity, the both-
12–71 months), with no significant points improvement with citrus honey,
ersome nature of the cough, the effect of
difference in age among the treatment and 1.70 points with labiatae honey,
the cough on sleep for both the child and
groups (Table 1). One hundred forty-six compared with a 1.21-point change
the parent, and the combined score of
these five measures.
of the children (54%) were boys. The with silan date extract (F = 3.61, P ,
participants were ill a mean 6 SD of .014). As might be expected, parental
2.8 6 2.0 days before enrollment, with sleep improved in a fashion similar to
Sample Size Analysis
no significant differences among treat- that of their children, with the honey-
On the basis of previously published ment groups (P = .161). Almost half treatment arms improving the most,
data,8 we estimated that the sample (47%) of the children had .3 days of a mean of 2.16 points with eucalyptus
size necessary to detect a 0.75-point dif- coughing, with no difference among honey, 2.10 points with citrus honey,
ference between any 2 treatment groups groups (P = .9). In addition, there were no 1.90 points with labiatae honey, and
(using analysis of variance) with 90% significant differences between mea- 1.28 points with silan date extract (F =
power and an a of .05 was 60 subjects sures of symptom severity at baseline. 3.40, P , .018). When the results for
per treatment group.
When symptom scores were compared these outcomes were combined by add-
To compensatefor possibledropoutsand for each treatment group from the night ing the scores from the individual cate-
abnormal data distribution, we attemp- before treatment to the night of treat- gories, honey again proved to be the
ted to recruit 75 patients per group. ment, significant differences were de- most effective treatment. The children
tected in the amount of improvement improved by an average of 9.88 points
Statistical Analysis reported for all study outcome varia- with eucalyptus honey, 10.10 points with
Statistical comparisons of variables bles (Fig 3). No significant differences citrus honey, 9.51 points with labiatae
between treatment groups were per- were found among the different types honey, compared with 5.82 points for
formed by using the x 2 test for nominal of honey; however, each of the honey those treated with silan date extract (F =
variables and analysis of variance for groups had a better response com- 5.33, P , .001).
continuous variables. For comparisons pared with the silan date extract. For Stomachache, nausea, or vomiting were
of cough evaluation before and after cough frequency, those who received reported by the parents of 4 patients in
treatment, a paired Student t test was eucalyptus honey had a mean 1.77- thehoneytreatmentgroup(2inthecitrus,
used. A P value ,.05 was considered point improvement compared with a 1 in the eucalyptus, and 1 in the labiatae
statistically significant. All statistical 1.95-point change for those receiving honey group) and 1 in the placebo group.
analyses were done by using the SPSS citrus honey, 1.82 change for those The adverse events were not significantly
package for Windows (version 15.0.1, receiving labiatae honey, and a 1.00 different between the groups.
SPSS, Chicago, IL). point change for those who were treated
with silan date extract (placebo group)
Ethics on the second night (F = 5.708, P , DISCUSSION
The study was approved by the Com- .001). Parents also noted similar im- The results of this study (Fig 3) dem-
mittee for Ethics in Human Subjects provements in the severity of their onstrate that each of the 3 types of
4 COHEN et al
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ARTICLE
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.
that have been suggested as the mech- that the darker a honey’s color, the the observed effect in patients treated
anism for honey’s efficacy in wound higher its antioxidant capacity. The with silan date extract because this
healing and may help to explain its su- levels of certain antioxidant compo- is also a sweet substance. However,
perior results in this study.16–21 nents decrease with processing and the significant difference between the
The antioxidants present in honey come storage of honey.21 However, available honey products and the silan date ex-
from a variety of sources, such as vi- data show that phenolic antioxidants tract suggests that other factors in
tamin C, monophenolics, flavonoids, from processed honey are bioavailable addition to the sweet taste of honey
and polyphenolics. Although there is a and increase the antioxidant activity of contribute to its beneficial effect on
wide spectrum of antioxidant types, plasma.19 children with cough.
monophenolicssuchas 4-hydroxybenzoic Eccles26 provided another possible ex- Silan was used as placebo in this study.
and 4-hydroxycinnamic acids predom- planation for some of the beneficial An alternative hypothesis is that silan
inate in many honeys.21,25 Most of the effects of honey. Because of the close date extract could worsen cough and
antioxidant components in processed anatomic relationship between the cold symptoms. However, our data
honey are water, not lipid, soluble.21 sensory nerve fibers that initiate cough clearly show that patients treated with
Different types of honey vary widely in and the gustatory nerve fibers that silan date extract actually improved.
the quantity of water-soluble antioxi- taste sweetness, an interaction be- There is also no reason to believe silan
dants they contain.26,27 This variability tween these fibers may produce an caused allergic symptoms or bron-
is dependent on the honey’s floral source, antitussive effect of sweet substances chospasm because dates are not a
as well as seasonal, environmental, and via a central nervous system mecha- common food allergen in the Israeli
other external factors. It was observed nism. This theory may explain some of population.27
6 COHEN et al
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ARTICLE
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