[PHNUTR-L] Zinc Supplementation Reduced Cost and Duration of Acute Diarrhea in Children

[Kathrynne Holden]

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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

http://www.vitasearch.com/CP/experts/GVGregorioAT09-28-07.htm

“Zinc Supplementation Reduced Cost and Duration of Acute Diarrhea in 
Children,”

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 
diarrhea.

  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 
diarrhea.

KH:    Were there any side effects with the zinc therapy? How was the 
patient compliance?

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 
considered non-compliant.

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 
6 months.

KH:    What would the savings be in morbidity and mortality from zinc 
therapy?

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 
maintenance organization.
-- 
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
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