Role of Zinc Supplementation in the Outcome of
Repeated Acute Respiratory Infections in Indian Children: A Randomized Double
blind Placebo-Controlled Clinical Trial
Debasis
Das Adhikari1*, Saibal Das2
1Physician, Paediatric
Emergency, Department of Paediatrics, Christian
Medical College, Vellore, 632 002, India
2PG Registrar, Department of Pharmacology, Christian
Medical College, Vellore, 632 002, India
*Corresponding Author E-mail: debasis@cmcvellore.ac.in
ABSTRACT:
This study was done to determine the role of zinc supplementation in the outcome of
acute respiratory infections in Indian children. This prospective,
double blind, randomized placebo-controlled trial was conducted with children
aged 6 months to 5 years having history of recurrent recent respiratory tract
infections. After recruitment, they were randomized to receive 10 mg zinc
sulfate or placebo once a day orally for 3 months and were followed monthly
up-to next 6 months. Serum zinc concentrations were estimated by colorimetry at the beginning and at the end of 3 months.
Zinc supplementation didn’t reduce the frequency or duration of respiratory
infections overall, but children with post-treatment serum zinc concentrations
> 70 mg/dl had significant better outcomes. Usefulness of zinc in improving
outcome of ARI in children is an unsolved puzzle and more prospective studies
correlating serum zinc concentrations periodically with frequency and duration
of ARI in larger cohort are warranted.
KEYWORDS: Zinc,
supplementation, acute respiratory infections, children.
INTRODUCTION:
Zinc deficiency
is a common micronutrient deficiency in children < 5 years in developing
countries leading to several immunological deficits. Many randomized trials and
meta analyses have shown that zinc supplementation both therapeutically and prophylactically reduces the duration, severity, and
incidence of acute respiratory infections (ARI).1However, some
trials done in India, Nepal, Bangladesh, and different parts of South-East Asia
have failed to prove the protective role of zinc in this regard.2 The
prospective, double blind, randomized, placebo-controlled trial was conducted
between 1 April 1998 and 31 January 1999 after obtaining approval from the
Institutional Review Board, to determine the effect of zinc supplementation on
the frequency and duration of ARI episodes in children.
Because of the recent controversy and confusing reports regarding the use
of zinc in children with ARI in different countries, we decided to bring
forward our findings. Children
of 6 months to 5 years age, with history of recurrent respiratory tract
infections (≥ 3 separate episodes in last 3 months or cough for ≥
15 days in last 3 months) were included. Children already on zinc
supplementation, immune-suppressive drugs, presence of congenital heart
diseases, HIV, chronic lung disease, tuberculosis, and diarrhea were excluded.
Recruited children were randomly divided into 2 groups, receiving orally, 10 mg
zinc sulfate per day after food or placebo for 3 months. They were followed up
monthly up to next 6 months following a standard protocol and maintaining a
symptom diary. Serum zinc estimation by colorimetry3was done at the
beginning and at the end of 3 months after treatment. The primary outcome
measure was the frequency and duration of ARI episodes during follow-up. Fox Base® data entry program was
used. Analysis was done with SPSS ® and Microsoft Excel ®. Student’s t-test and
chi-square tests were used and p<
0.5 was considered significant. 34 children aged 6 months to 5 years were
included. 15 were randomized in the treatment arm and 19 in the placebo. 3
children in the placebo arm didn’t return for follow-up and were excluded.
There was no statistically significant difference in pre and post-treatment
serum zinc concentrations between the 2 groups. There was no significant
difference in the mean frequency and duration of ARI episodes between the 2
groups, even after stratifying according to pre and post-treatment zinc
concentrations. However, there was significant improvement (p = 0.045) in the frequency of ARI
episodes in children with serum zinc concentration > 70 mg/dl as compared to
placebo. But, because of the marginal significance attained and lower sample
size, the protective role of zinc couldn’t be claimed confirmedly. Not
many studies done so far checked for serum zinc concentrations and correlated
with ARI outcomes in children. Our finding is at par with some similar studies4,5
which also showed that low serum zinc concentration is significantly associated
with higher incidences of ALI (including pneumonia and bronchiectasis)
in children. More prospective studies correlating serum zinc concentrations
periodically with frequency and duration of ARI in larger cohort are warranted.
CONFLICTS OF INTERESTS:
All authors have
none to declare.
FUNDING:
The author(s) received no financial support for the
research, authorship, and/or publication of this article.
ACKNOWLEDGEMENT:
We gratefully acknowledge the contributions of Dr. Swaminathan, Department of Clinical Biochemistry, Christian
Medical College, Vellore for performing the zinc assays; Dr. Jeyaseelan and Dr. Jamaluddin,
Department of Biostatistics, Christian Medical College, Vellore for helping in
the statistical analysis; the Hospital Pharmacy, Christian Medical College,
Vellore for preparing the study drugs and placebo; and the nursing staffs of
Pediatrics Outpatient Department, Christian Medical College, Vellore for
helping in data collection.
REFERENCES:
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Walker CL, Rudan I, Liu L,
Nair H, Theodoratou E, Bhutta
ZA, O'Brien KL,
Campbell H,
Black RE.
Global burden of childhood pneumonia and diarrhoea.
Lancet. 2013;381:1405-16.
2.
Umeta M, West CE, Haidar J, Deurenberg P, Hautvast JG. Zinc supplementation and stunted infants in
Ethiopia: a randomised controlled trial. Lancet.
2000;355:2021–6.
3. Johnson DJ, Djuh YY, Bruton J, Williams HL. Improved
colorimetric determination of serum zinc. Clin Chem. 1977;23:1321-3.
Received on 12.02.2016 Modified on 25.02.2016
Accepted on 18.03.2016 © RJPT All right reserved
Research J.
Pharm. and Tech. 9(4): April, 2016; Page 457-458
DOI: 10.5958/0974-360X.2016.00084.6