[PHNUTR-L] Zinc Supplementation Reduced Cost and Duration of Acute
Diarrhea in Children
fivestar at nutritionucanlivewith.com
Tue Oct 30 08:10:14 PDT 2007
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Diarrhea and Zinc Supplementation
Germana V. Gregorio, M.D.
Department of Pediatrics
University of the Philippines College of Medicine
Philippine General Hospital
Taft Avenue, Manila, Philippines
(632) 524 0892 / (632) 526 0150 (FAX)
germana1 at hotmail.com
“Zinc Supplementation Reduced Cost and Duration of Acute Diarrhea in
J Clin Epidemiol, 2007 Jun;60(6):560-6. Epub 2006 Dec 11. 45975 (10/2007)
Kirk Hamilton: Can you please share with us your educational
background and current position?
Germana V. Gregorio: I am a Doctor of Medicine with specialty
training in the field of pediatric gastroenterology. I am presently a
Clinical Associate Professor in the Department of Pediatrics, University
of the Philippines College of Medicine, Philippine General Hospital.
KH: What got you interested in studying the role of zinc and acute
diarrhea in children?
GVG: It is not clear why some episodes of diarrhea persist for a longer
duration in some patients as compared with others but host factors, such
as nutritional deficiencies, which may increase susceptibility to
enteric infections and delay mucosal recovery would be expected to
contribute to this effect. Two well-documented determinants of diarrheal
duration are low weight-for-age and decreased cell-mediated immunity.
Common to both of these factors are zinc deficiency, which is prevalent
in children in developing countries.
KH: What is the biochemistry of zinc that might lead to a resolution
in acute diarrhea?
GVG: Zinc is an essential trace element for humans, being a constituent
of over 200 metalloenzymes. Zinc participates in major metabolic
pathways involving tissue and protein synthesis and turnover,
carbohydrates and energy metabolism, gene expression, embryogenesis and
apoptosis. Zinc is thus essential for growth, sexual maturation and
immune function. Zinc supplementation has been shown to improve immune
function and to reduce the incidence and prevalence of diarrhea among
children in developing countries. Possible roles for zinc include
regulation of intestinal water and electrolyte transport, improvement in
the enzymatic function of the brush borders and enhancement of the
repair of the intestinal mucosa, leading to a decreased duration of
KH: What were the dose, frequency and type of zinc used? What was
the elemental amount of zinc given daily? Was it given in a liquid or
tablet form? With meals or away from meals?
GVG: The zinc tablets were in the form of zinc sulfate. It contains 20
mg elemental zinc given once daily for 14 days. The zinc tablets were
dissolved in water or milk before administration or were taken as is by
older children. The tablets were taken 2 hours after food intake.
KH: Were zinc levels sub-optimal in these children with acute
diarrhea? If so, did those supplemented with zinc and who recovered,
have documented improvement in zinc levels?
GVG: The present study did not measure the zinc levels of the patients
before and after administration. However, previous studies have
documented an improvement in the zinc levels (and a shorter duration of
the diarrhea) after supplementation
KH: Can you tell us about your study and the basic results?
GVG: The study included children aged between 2 to 59 months with a
history of diarrhea <7 days duration and no dehydration. Patients were
randomized to either the zinc supplemented or no treatment group. The
clinical outcome of interest was duration of diarrhea. The following
data on resources used and clinical outcomes were obtained during
randomization and on follow-ups during the first and second weeks: (1)
direct medical costs (building space, drugs, diagnostics and
professional fees); (2) direct non-medical costs (out-of-pocket
expenditures); (3) indirect cost (salary lost for parents or
caregivers); (4) compliance with medications; and (5) date of cessation
of diarrhea. The mean duration of diarrhea was shorter and the mean
total cost of treatment was 5% cheaper in the zinc treated group than in
the no treatment group. After computing for the cost effectiveness
ratio, it was shown that zinc supplementation as compared to no
treatment is more cost effective in the treatment of acute childhood
KH: Were there any side effects with the zinc therapy? How was the
GVG: The study did not observe any patient with vomiting after intake of
zinc, which is the known side effect of the drug. In a trial done in
Nepal, it was shown that the relative risk of vomiting increases by 3 to
4 times if children are given 3 times the RDA (15 and 30 mg) for zinc.
In this study, non-compliance with intake of zinc was defined as < 80%
intake of the recommended dose. This was assessed by counting the number
of remaining zinc tablets during the follow-up visits of the patient and
by asking the caregivers if they had given the zinc tablets to someone
else apart from the study patient. In the study, no patient was
KH: In your opinion, should all cases of childhood diarrhea (acute)
be treated with a zinc supplement? How do you determine what dose to
give and who gets treated with zinc?
GVG: It is clear in different studies and in a meta-analysis that zinc
supplementation causes a reduction in the duration of diarrhea. In June
2004, a joint statement made by the WHO and UNICEF advocated the use of
zinc as an adjunctive therapy in acute childhood diarrhea. The WHO
recommends giving 20 mg/day of elemental zinc for 10-14 days in children
with diarrhea but the dose is reduced to 10 mg/day in infants less than
KH: What would the savings be in morbidity and mortality from zinc
GVG: Based on the outcomes that were measured in the trial, it was not
possible to assess the savings in terms of morbidity and mortality from
zinc treatment in acute diarrhea. However, in another study, it was
shown that the mean incremental cost effectiveness ratio was reduced
from US$113 to US$73 per disability adjusted life years (DALY) averted
when zinc is given.
KH: Do you have any further comments that you would like to make on
this very practical treatment?
GVG: It is recommended that further studies on cost-effectiveness
analysis of zinc supplementation in acute diarrhea be done using a
different costing method to validate the results of this study. The cost
of the present study was derived from the cost figures of an urban,
government, tertiary hospital. The cost figures of private hospitals or
rural, government hospitals could be used. Likewise, the cost in this
study was done from the society’s perspective. It will be of interest to
do an evaluation from the perspective of the patient or a health
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