Sao Paulo Med J. 2011;129(2):118-9
Oral zinc for treating diarrhoea in children
Marzia Lazzerini, Luca Ronfani
“This review should be cited as:
Lazzerini Marzia, Ronfani Luca. Oral zinc for treating diarrhoea in children. Cochrane
Database of Systematic Reviews. In: The Cochrane Library, Issue 10, Art. No.
CD005436. DOI: 10.1002/14651858.CD005436.pub3.
The independent commentary is written by Mauro Batista de Morais.”
BACKGROUND: Diarrhoea causes around two million child
deaths annually. Zinc supplementation could help reduce the duration
and severity of diarrhoea, and is recommended by the World Health
Organization and UNICEF.
OBJECTIVE: To evaluate oral zinc supplementation for treating
children with acute or persistent diarrhoea.
CRITERIA FOR CONSIDERING STUDIES FOR THIS RE-
VIEW: In November 2007, we searched the Cochrane Infectious Dis-
eases Group Specialized Register, CENTRAL (The Cochrane Library
2007, Issue 4), MEDLINE, EMBASE, LILACS, CINAHL, mRCT,
and reference lists. We also contacted researchers.
SELECTION CRITERIA: Randomized controlled trials com-
paring oral zinc supplementation (≥ 5 mg/day for any duration) with
placebo in children aged one month to five years with acute or persistent
diarrhoea, including dysentery.
DATA COLLECTION AND ANALYSIS: Both authors assessed
trial eligibility and methodological quality, extracted and analysed
data, and drafted the review. Diarrhoea duration and severity were the
primary outcomes. We summarized dichotomous outcomes using risk
ratios (RR) and continuous outcomes using mean differences (MD)
with 95% confidence intervals (CI). Where appropriate, we combined
data in meta-analyses (using the fixed- or random-effects model) and
MAIN RESULTS: Eighteen trials enrolling 6165 participants met
our inclusion criteria. In acute diarrhoea, zinc resulted in a shorter
diarrhoea duration (MD -12.27 h, 95% CI -23.02 to -1.52 h; 2741
children, 9 trials), and less diarrhoea at day three (RR 0.69, 95% CI
0.59 to 0.81; 1073 children, 2 trials), day five (RR 0.55, 95% CI 0.32
to 0.95; 346 children, 2 trials), and day seven (RR 0.71, 95% CI 0.52
to 0.98; 4087 children, 7 trials). The four trials (1458 children) that
reported on diarrhoea severity used different units and time points,
and the effect of zinc was less clear. Subgroup analyses by age (trials
with only children aged less than six months) showed no benefit with
zinc. Subgroup analyses by nutritional status, geographical region,
background zinc deficiency, zinc type, and study setting did not affect
the results’ significance. Zinc also reduced the duration of persistent
diarrhoea (MD -15.84 h, 95% CI -25.43 to -6.24 h; 529 children, 5
trials). Few trials reported on severity, and results were inconsistent. No
trial reported serious adverse events, but vomiting was more common
in zinc-treated children with acute diarrhoea (RR 1.71, 95% 1.27 to
2.30; 4727 children, 8 trials).
AUTHORS’ CONCLUSIONS: In areas where diarrhoea is an
important cause of child mortality, research evidence shows zinc is
clearly of benefit in children aged six months or more.
PLAIN LANGUAGE SUMMARY: In developing countries, mil-
lions of children suffer from severe diarrhoea every year. This is due to
infection and malnutrition, and many die from dehydration due to the
diarrhoea. Giving fluids by mouth (using an oral rehydration solution)
has been shown to save children’s lives, but it seems to have no effect
on the length of time the children suffer with diarrhoea. Children in
developing countries are often zinc deficient. Zinc supplementation is
a possible treatment for diarrhoea though it can have adverse effects if
given in high doses. The review of trials identified 18 trials involving
6165 children of all ages. Zinc reduced the time that children over
the age of six months suffered from symptoms of acute or persistent
diarrhoea. However, there were insufficient data to see any impact on
the number of children who died. More children vomited when given
zinc, but it was considered that the benefits outweighed these adverse
effects. Zinc seemed to have no impact on children aged less than six
months. In areas where diarrhoea is an important cause of child mortal-
ity, research evidence shows zinc is clearly of benefit in children aged
six months or more with diarrhoeal diseases.
Brazilian Cochrane Center
Rua Pedro de Toledo, 598
Vila Clementino — São Paulo (SP) — Brasil
Tel. (+55 11) 5575-2970
This section was edited under the responsibility of the Brazilian Cochrane Center
During the 20th century, oral rehydration therapy for children suf-
fering from diarrhea was developed and applied in an effective manner.
This has been considered to be the therapeutic method that singly saved
the largest number of lives during that century. Thus, the two pillars
of treatment for acute diarrhea and persistent diarrhea (i.e. the form
that begins with an episode of acute diarrhea, of presumably infectious
origin, and extends for longer than 14 days, in children less than five
years of age, and brings about negative repercussions on nutritional
status) became solidified: 1. oral rehydration therapy; and 2. prevention
and combating of malnutrition through adequate feeding.
Starting from this point, space was created such that the main
therapeutics for acute diarrhea were broadened towards additional ob-
jectives, especially reduction of the duration of diarrhea and reduction of
abnormal fecal losses. To this end, clinical research focused on the thera-
peutic role of zinc, probiotics and intestinal secretion reducers such as
racecadotril, bismuth subsalicylate and vitamin A, among others. These
therapeutic measures, used in conjunction with nutritional care and oral
rehydration, were recently analyzed in detail in the Guidelines of the
European Society for Pediatric Gastroenterology, Hepatology and Nu-
trition1 and in the Iberian-Latin American Clinical Practice Guide.2
The systematic review and meta-analysis by Lazzerini and Ronfani3
demonstrated that zinc administration is associated with mean reduc-
tions in the duration of acute diarrhea and persistent diarrhea of 12.3
hours and 15.8 hours, respectively, for children between the ages of six
months and five years. Considering that the clinical trials were carried
Sao Paulo Med J. 2011;129(2):118-9
out in underdeveloped countries, the authors concluded that in areas in
which diarrhea is an important cause of mortality among infants and
young children, the scientific evidence indicates that zinc therapy is ef-
ficient. Furthermore, the World Health Organization (WHO) considers
that zinc reduces the future risk of a new diarrhea outbreak during the
subsequent two to three months. The addition of such measures within
the Brazilian public health scenario requires a cost-effectiveness analysis
that takes into consideration the need for preparation and distribution
of zinc-containing products, in the same way in which oral rehydration
salts were investigated in the past.
1. Guarino A, Albano F, Ashkenazi S, et al. European Society for Paediatric Gastroenterology,
Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-
based guidelines for the management of acute gastroenteritis in children in Europe. J Pedia-
tr Gastroenterol Nut. 2008;46 Suppl 2:S81-122.
Gutiérrez Castrellón P; Polanco Allué I; Salazar Lindo E. Manejo de la gastroenteritis agu-
da en menores de 5 años: un enfoque basado en la evidencia Guía de práctica clínica
Ibero-Latinoamericana. An Pediatr (Barc) 2010;72:1-19. Available from: http://xa.yimg.
a±de±gastroenteritis±en±ni%C3%B1os±menores±de±5a%C3%B1os.pdf. Accessed in
2010 (Dec 21).
Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Data base
Syst Rev. 2008;(3):CD005436. Available from: http://www.cochranejournalclub.com/
probiotics-acute-infectious-diarrhoea-clinical/pdf/CD005436_standard.pdf. accessed in
2011 (Apr 18).
Mauro Batista de Morais. President of the Department of Gastroenterology, Sociedade
de Pediatria de São Paulo, and Associate Full Professor of the Discipline of Pediatric
Gastroenterology and Head of the Department of Pediatrics, Universidade Federal de
São Paulo — Escola Paulista de Medicina (Unifesp-EPM), São Paulo, Brazil.