Departments of 1Pediatrics and 4Statistics and Centres for 2Cellular & Molecular Research and 3Metabolic Diseases Research, Qazvin University of Medical
Sciences, Qazvin, Iran
*Corresponding Author e-mail: abolfazl473@yahoo.com
مستوى معدن الزنك يف مصل دماء األطفال املصابني بإسهال
َدَموّي أو مائي حاد
اأبو الفا�سل مهيار، بارفيز اأبازي، فيكتوريا فقيني، مهدي �ساهماين، �سونيا اأوفيزي، �سيفا اإ�سماعيلي
abstract: Objectives: The role of zinc in the pathogenesis of diarrhoea is controversial. This study was conducted
to compare serum zinc levels in children with acute diarrhoea to those found in healthy children. Methods: This
case-control study was carried out at the Qazvin Children’s Hospital in Qazvin, Iran, between July 2012 and January
2013. A total of 60 children with acute diarrhoea (12 children with bloody diarrhoea and 48 children with watery
diarrhoea) and 60 healthy children were included. Zinc levels for all subjects were measured using a flame atomic
absorption spectrophotometer and data were analysed and compared between groups. Results: Mean serum zinc
levels in the patients with acute bloody diarrhoea, acute watery diarrhoea and the control group were 74.1 ± 23.7
µg/dL, 169.4 ± 62.7 µg/dL and 190.1 ± 18.0 µg/dL, respectively (P = 0.01). Hypozincaemia was observed in 50.0% of
children with acute bloody diarrhoea and 12.5% of those with acute watery diarrhoea. None of the patients in the
control group had hypozincaemia (P = 0.01). Conclusion: Children with acute bloody diarrhoea had significantly
reduced serum zinc levels in comparison to healthy children. However, a study with a larger sample size is needed
to examine the significance of this trend.
Keywords: Zinc; Diarrhea; Children; Case-Control Study; Iran.
دماء م�سل يف الزنك م�ستوى ملقارنة الدرا�سة هذه هدفت خالفيا. اأمرا الإ�سهال فيمر�ض الزنك يلعبه الذي الدور يعد الهدف: امللخ�ص:
الأطفال امل�سابني باإ�سهال َدَموّي اأو مائي حاد مع م�ستواه عند الأطفال الأ�سحاء. الطريقة: اأجريت هذه الدرا�سة ال�ستعادية يف م�ست�سفى
و12 مائي باإ�سهال 48( حاد مائي اأو َدَموّي باإ�سهال م�سابني طفال 60 الدرا�سة و�سملت .2013 ويناير 2012 يوليو بني باإيران قزوين
الذري، المت�سا�ض لهب مطياف جهاز طريق عن الأطفال هوؤلء م�سل يف الزنك تركيز قيا�ض ومت �سحيحا. طفال و60 دموي( باإ�سهال
وحللت النتائج ومتت املقارنة بني املجموعات. النتائج: وجد اأن متو�سط تركيز الزنك يف م�سل دماء الأطفال امل�سابني بالإ�سهال الدموي،
وبالإ�سهال املائي، والأ�سحاء كان µg/dL 23.7 ± 74.1 و µg/dL 62.7 ± 169.4 و µg/dL 18.0 ± 190.1، على التوايل )P = 0.01( . ولوحظ
اأن %50.0 من الأطفال امل�سابني باإ�سهال َدَموّي حاد، و %12.5 من الأطفال امل�سابني باإ�سهال مائي حاد كانوا يعانون من حالة قلة
الزنك تركيز يف اإح�سائيا معنوي نق�ض من حاد دموي باإ�سهال امل�سابون الأطفال يعاين اخلال�صة: .)P = 0.01( الدم يف الزنك تركيز
يف م�سل الدم عند مقارنتهم بالأطفال الأ�سحاء. غري اأنه ملعرفة اأهمية هذه النتيجة ودللتها، يجب القيام بدرا�سة اأخرى بعدد اأكرب من
العينات.
مفتاح الكلمات: زنك؛ اإ�سهال؛ درا�سة حالة �سابطة؛ الأطفال؛ اإيران.
Serum Zinc Concentrations in Children with Acute
Bloody and Watery Diarrhoea
*Abolfazl Mahyar,1 Parviz Ayazi,1 Victoria Chegini,1 Mehdi Sahmani,2 Sonia Oveisi,3 Shiva Esmaeily4
clinical & basic research
Advances in Knowledge
- The results of the present study confirm the role of zinc in the pathophysiology of acute diarrhoea, particularly for patients with acute
bloody diarrhoea.
Application to Patient Care
- The findings of this study may inform treatment regimens for children with diarrhoea, as the addition of zinc supplementation may help
children recover more rapidly.
Sultan Qaboos University Med J, November 2015, Vol. 15, Iss. 4, pp. e512–516, Epub. 23 Nov 15
Submitted 15 Dec 14
Revisions Req. 9 Mar & 21 May 15; Revisions Recd.23 Mar & 22 May 15
Accepted 22 Jul 15 doi: 10.18295/squmj.2015.15.04.012
Diarrhoea is defined by the World Health Organization as the excretion of loose or watery stool at least three times
within 24 hours.1 Acute diarrhoea occurs over a
few hours or days with a total duration of less than
14 days. It is divided into two types: watery and
bloody diarrhoea (dysentery). The main causes of
acute diarrhoea include rotavirus, enteroinvasive
Escherichia coli, Shigella and Salmonella.1–3 Diarrhoea
is a common condition in children. Based on available
data, 2.5 billion diarrhoea cases occur per year
among children under five years of age in developing
countries.4 More than 80% of these cases are observed
in Asia and Africa, where the incidence of diarrhoea
Abolfazl Mahyar, Parviz Ayazi, Victoria Chegini, Mehdi Sahmani, Sonia Oveisi and Shiva Esmaeily
Clinical and Basic Research | e513
is 3.6 episodes annually per child.1,3,4 Diarrhoea is
a significant cause of child mortality worldwide,
particularly in developing countries; Boschi-Pinto et al.
estimated that approximately 1.8 million deaths each
year are diarrhoea-related, with most of these deaths
occurring in children under five years old.5
Micronutrient deficiency is still a notable cause
of mortality among patients with diarrhoea despite
the introduction of oral rehydration salts (ORS).6–12
Furthermore, micronutrient deficiency is known to
exacerbate diarrhoea and delay recovery time, causing
the condition to become chronic.6–12 Zinc is one of the
most important micronutrients and is crucial for free
radical detoxification, antioxidant defence and immune
system function in humans.13,14 Zinc levels have been
found to be reduced in patients with acute diarrhoea.6,15
Despite these findings, there is disagreement regarding
the efficacy of zinc supplementation for children with
acute diarrhoea. Some studies have reported that zinc
supplementation accelerates recovery and reduces
the duration and severity of diarrhoea, consequently
reducing mortality;16–18 however, other studies do not
support these findings.19–23 Due to this controversy
and the high prevalence of acute diarrhoea in Iranian
children, this study was conducted to determine
serum zinc levels in children with acute diarrhoea in
Qazvin, Iran.
Methods
This case-control study was carried out at the Qazvin
Children’s Hospital in Qazvin between July 2012
and January 2013. Inpatients ≤5 years old who were
admitted to the Emergency or Paediatric wards
of the Qazvin Children’s Hospital due to severe/
acute diarrhoea, diarrhoea with vomiting and/or a
fever during the study period were included. Acute
diarrhoea was defined as the excretion of loose or
watery stools at least three times within 24 hours,
developing over a few hours or days and lasting fewer
than 14 days.1 Patients with chronic diarrhoea lasting
more than 14 days and occurring in conjunction
with other underlying diseases such as malnutrition,
diabetes, urinary tract infections, septicaemia, pneu-
monia and other skin or metabolic diseases were
excluded from the study. Group matching was used
to select the control group from healthy children who
were referred to the health centre of the same hospital
for evaluation of their growth. Children in both
groups resided in Qazvin Province and were similar in
age and gender.
The sample size was calculated according to the
following formula:24
Where α is 0.05, 1-α/2 is 0.95, β is 0.2, 1-β2 is 0.8, σ
is 8, µ1 is 79 µg/dL and µ2 is 83 µg/dL. Consecutive
sampling was used until the desired sample size was
reached. A total of 60 children with acute diarrhoea
and 60 healthy children were included. The children
with acute diarrhoea were divided into watery (n = 48)
and bloody (n = 12) diarrhoea groups. The children
with acute diarrhoea were also subdivided according
to dehydration severity into mild (<5%), moderate
(5–10%) and severe (>10%) groups.3,25
The demographic information and symptoms of all
subjects were recorded. Prior to beginning treatment
for diarrhoea, blood samples from the experimental
group were analysed to measure erythrocyte sedi-
mentation rates and C-reactive protein levels and
white blood cell, neutrophil and platelet counts. All
tests were performed in the Laboratory Department of
Qazvin Children’s Hospital using standard methods. To
measure serum zinc levels, 3 mL of blood were drawn
from the peripheral vessels of all of the children. Serum
was obtained by centrifugation at 3,000 revolutions per
minute for five minutes at 4 °C. The serum was then
poured into acid-washed tubes and stored in a freezer
at -20 °C until the serum zinc assays were completed.
Serum zinc levels were then measured using a flame
atomic absorption spectrophotometer (GBC Scientific
Equipment Pty Ltd, Braeside, Victoria, Australia) in
the Biochemistry Department of Qazvin University of
Medical Sciences in Qazvin. Levels of 70–120 µg/dL
were considered to indicate a normal range and
levels of less than 70 µg/dL were considered to
indicate hypozincaemia.26
Data were entered into the Statistical Package for
the Social Sciences (SPSS), Version 16 (IBM Corp.,
Chicago, Illinois, USA). The results were analysed
using Chi-squared and Tukey’s post hoc tests and
Spearman’s rank correlation coefficient and Pearson’s
correlation coefficient analyses. A value of P <0.05 was
considered statistically significant.
This study was approved by the Ethics Committee
of the Research Department at the Qazvin University
of Medical Sciences (project #303). The parents of
all subjects gave written informed consent for their
inclusion in the study.
n = 2(z[1- ]+z[1-β])2σ2
(µ1-µ2)
2
α
2
Serum Zinc Concentrations in Children with Acute Bloody and Watery Diarrhoea
e514 | SQU Medical Journal, November 2015, Volume 15, Issue 4
Table 1: Demographic data of children with acute diarr-
hoea in comparison to an age- and gender- matched
control group in Qazvin, Iran (N = 120)
Variable Acute
diarrhoea
group
(n = 60)
Control
group
(n = 60)
P
value
Male-to-female
ratio*
37:23 38:22 0.99
Mean age in
months ± SD†
28.8 ± 15.2 30.1 ± 15.5 0.65
Mean weight in
kg ± SD†
12.3 ± 3.1 12.8 ± 2.9 0.80
Height in cm
± SD†
88.9 ± 12.1 89.3 ± 11.6 0.90
Median head
circumference
in cm ± IQR‡
46 ± 2.0 46 ± 3.0 0.73
SD = standard deviation; IQR = interquartile range.
*Calculated using the Chi-squared test. †Calculated using the Student’s
t-test. ‡Calculated using the Mann-Whitney U-test.
Table 2: Characteristics of diarrhoeal illness among
children with acute diarrhoea in Qazvin, Iran (N = 60)
Characteristic n (%)
Type of diarrhoea*
Watery 48 (80.0)
Bloody 12 (20.0)
Mean frequency ± SD† 6.0 ± 1.5
Mean duration of illness in days ± IQR‡ 2.1 ± 1.0
Dehydration severity*§
Mild 17 (28.3)
Moderate 30 (50.0)
Severe 13 (21.7)
Symptoms
Fever 48 (80.0)
Vomiting 34 (56.7)
Abdominal pain 21 (35.0)
Lack of appetite 16 (26.7)
Stool culture results
No growth 32 (53.3)
Pathogenic Escherichia coli 15 (25.0)
Shigella 10 (16.7)
Salmonella 3 (5.0)
SD = standard deviation; IQR = interquartile range.
*Calculated using the Chi-squared test. †Calculated using the student’s
t-test. ‡Calculated using the Mann-Whitney U test. §Dehydration
severity was classified into mild (<5%), moderate (5–10%) and severe
(>10%) categories.
Table 3: Mean serum zinc levels and hypozincaemia among children
with acute diarrhoea in comparison to an age- and gender- matched
control group in Qazvin, Iran (N = 120)
Acute diarrhoea group Control
group
(n = 60)
P
value
Bloody
(n = 12)
Watery
(n = 48)
Mean zinc ± SD
in µg/dL*
74.1 ± 23.7 169.4 ± 62.7 190.1 ± 18.0 0.01
Hypozincaemia,†
n (%)‡
6 (50.0) 6 (12.5) 0 (0.0) 0.01
SD = standard deviation.
*Calculated using the Tukey’s post hoc test. †Serum zinc levels of <70 µg/dL. ‡Calculated
using the Chi-squared test.
Table 4: Serum zinc levels according to causative organism
of bacterial acute diarrhoea among children in Qazvin, Iran
(N = 28)
Zinc in
µg/dL
Causative organism P
value
Pathogenic
Escherichia
coli
(n = 15)
Shigella
(n = 10)
Salmonella
(n = 3)
Minimum 50.0 50.0 155.0 0.01
Maximum 95.0 120.0 180.0
Mean ± SD 74.0 ± 13.2 74.0 ± 25.0 170.0 ± 13.2
SD = standard deviation.
Table 5: Correlation between serum zinc levels and inflamm-
atory and non-inflammatory variables among children with
acute diarrhoea in Qazvin, Iran (N = 60)
Variables Serum zinc levels
Acute
diarrhoea
(n = 60)
Acute watery
diarrhoea
(n = 48)
Acute bloody
diarrhoea
(n = 12)
R P
value
R P
value
R P
value
Inflammatory
Fever -0.43 0.01 -0.26 0.06 -0.20 0.40
WBC -0.68 0.01 -0.52 0.01 -0.24 0.40
Neutrophils -0.74 0.01 -0.62 0.01 -0.42 0.16
ESR -0.83 0.01 -0.78 0.01 -0.50 0.06
CRP -0.82 0.01 -0.75 0.01 -0.27 0.30
Non-inflammatory
Dehydration
severity
0.52 0.01 0.6 0.01 -0.24 0.40
Type of
diarrhoea
-0.52 0.01 - - - -
Causative
organism
-0.86 0.01 - - - -
WBC = white blood cell count; ESR = erythrocyte sedimentation rate;
CRP = C-reactive protein.
Abolfazl Mahyar, Parviz Ayazi, Victoria Chegini, Mehdi Sahmani, Sonia Oveisi and Shiva Esmaeily
Clinical and Basic Research | e515
Results
A total of 60 children with acute diarrhoea and 60
healthy children were included. There were 37 males
(61.7%) and 23 females (38.3%) among the acute
diarrhoea group, while the control group had 38 males
(63.3%) and 22 females (36.7%). Subjects in the diarrhoea
group ranged from 3–60 months old while those in the
control group ranged from 3–57 months old. There was
no significant difference between the groups in terms
of age, gender, weight, height or head circumference
(P >0.05) [Table 1].
Diarrhoeal illness characteristics of the patients
with acute diarrhoea are shown in Table 2. Of the 60
children with acute diarrhoea, 12 had bloody diarrhoea
and 48 had watery diarrhoea. The mean serum zinc
levels among those in the acute bloody diarrhoea,
acute watery diarrhoea and control groups were 74.1 ±
23.7 µg/dL, 169.4 ± 62.7 µg/dL and 190.1 ± 18.0 µg/dL,
respectively (P = 0.01). Hypozincaemia was observed
in 50.0% of the children with acute bloody diarrhoea
and 12.5% of the children with acute watery diarrhoea.
However, none of the children in the control group
had hypozincaemia (P = 0.01) [Table 3].
Among the children with acute diarrhoea, 28
were found to have bacterial diarrhoea caused by the
following organisms: E. coli (n = 15), Shigella (n = 10)
and Salmonella (n = 3). A significant difference was
observed in the mean serum zinc levels of these
patients (P = 0.01) [Table 4]. Correlations between
serum zinc levels and inflammatory and non-
inflammatory variables among children with acute
diarrhoea is shown in Table 5.
Discussion
Zinc is an essential nutrient for humans and plays
an important role in immunological processes and
the adequate functioning of many macromolecules.
Hypozincaemia can cause various diseases, including
acute diarrhoea, by disrupting the defence system
and reducing antioxidant activity.27 Some researchers
believe that the administration of zinc to patients with
diarrhoea accelerates their recovery by facilitating
rapid regeneration of the intestinal epithelium and
increasing brush border (apical) enzymes.18,27 This
provides a zinc transporter for enterocytes and
enhances the immune response. The result of these
pathophysiological changes is the improvement of
water and electrolyte absorption, as well as the faster
removal of pathogenic organisms from the intestine.18,27
Although the exact mechanism of zinc in water and
electrolyte transportation in the intestine is not clear,
this effect may be due to the inhibition of adenosine
3’,5’-cyclic monophosphate-induced chloride-depen-
dent fluid secretion in the small intestine.27
In the current study, children with acute bloody
diarrhoea had significantly lower serum zinc levels
in comparison with healthy children. Additionally,
hypozincaemia was observed in half of the children
with acute bloody diarrhoea and some of those with
acute watery diarrhoea while none of the control
group had hypozincaemia. This reduction in serum
zinc levels may be related to either the excretion
of zinc following acute diarrhoea or metabolic
reactions against the infections (known as acute phase
responses) or both.15,20,28,29
Many studies have reported contradictory results
on the effect of zinc in the treatment of acute diarrhoea.
A study of 3–59-month-old children affected with
acute diarrhoea in Bangladesh indicated that the
daily administration of 20 mg of zinc reduced the
duration and frequency of diarrhoea.16 Al-Sonboli et
al. also found that the administration of zinc reduced
the duration of diarrhoea among Brazilian children
<5 years old.17 A study by Bahl et al. in India revealed
that the administration of zinc along with ORS
reduced the severity of acute diarrhoea among
children between 6–35 months old.18 In contrast, Patel
et al. demonstrated that the administration of zinc
did not affect the duration of or rate of complications
arising from acute diarrhoea among children aged
6–59 months receiving either ORS and zinc or ORS
and a placebo.20 The researchers suggested that
the inefficacy of zinc in their study may have been
attributable to a low dose of zinc, poor compliance and
the failure of the supplements to replenish the zinc
loss.20 Other studies have confirmed these results.21–23
The primary limitation of the current study was
the failure to measure serum zinc concentrations
after patients had completed their course of
treatment. Additionally, the sample size was small.
As a result, future studies with a larger sample size
are recommended to assess the efficacy of zinc
supplementation among patients with acute diarrhoea.
Conclusion
The results of this study showed a trend towards
reduced serum zinc levels in children with acute
bloody diarrhoea as compared with healthy children in
a control group. However, a study with a larger sample
size is needed to study the significance of this trend
and to resolve the on-going controversy regarding the
efficacy of zinc supplementation as a treatment option
for individuals with acute diarrhoea.
Serum Zinc Concentrations in Children with Acute Bloody and Watery Diarrhoea
e516 | SQU Medical Journal, November 2015, Volume 15, Issue 4
a c k n o w l e d g e m e n t s
The researchers would like to thank the participants
and their parents for their cooperation in this study.
c o n f l i c t o f i n t e r e s t
The authors declare no conflicts of interest.
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http://dx.doi.org/10.1016/S0140-6736%2810%2960549-1
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