Importance of ZINC in preventing diarrhoea and Pneumonia

Zinc and pneumonia




K Michael Hambidge

Recent experience with lower mortality and morbidity due toinfectious
disease in well-designed, randomized, controlledtrials of zinc
supplements in young children has highlightedzinc deficiency as a
public health problem of global proportions^. This experience applies
especially to diarrhea and pneumonia,the most prevalent causes
worldwide of infectious disease mortalityin young children. The
most extensive and impressive data relateto the use of zinc as a
preventive measure. A pooled analysisof the results of trials in 9
countries and on 4 continentsshowed odds ratios (ORs) in
zinc-supplemented groups of 0.82(95% CI: 0.72, 0.93) and 0.75
(0.63, 0.88) for diarrheal incidenceand prevalence, respectively .
The data for pneumonia preventionwere even more impressive: the OR
was 0.59 (0.41, 0.83). Moreover,the use of zinc supplements as a
preventive modality has beenassociated with lower mortality,
notably that due to pneumonia.

Zinc administered as a therapeutic agent to young children withacute
or persistent diarrhea also reduces the duration of thediarrhea and
is associated with a lower rate of treatment failureor death .
However, results of studies of zinc administeredas adjuvant therapy
for pneumonia have been more limited. Ina recent study in Bangladesh,
zinc given together with antimicrobialtherapy to young children
with pneumonia was associated witha significant reduction in the
duration of pneumonia comparedwith that in the control group, who
received the same antimicrobialtherapy but no zinc . Comparable
benefits of zinc supplementation,although not identical in the
affected variables, were reportedfrom a study in Kolkarta, India,
but in male children only .In this issue of the Journal, Bose et al
report no benefitsof a zinc
supplement in the management of pneumonia in youngchildren in Tamilnadu, India.
Although they were quite thoroughin reviewing factors that may have
accounted for their negativeresult, no apparent explanation was
forthcoming.

A pharmacologic effect of zinc is plausible, but, as inthe
report by Bose et al, it is widely accepted that the beneficialeffects of zinc supplements in the prevention
and treatmentof diarrhea and pneumonia are most likely to be due to
the preventionor correction of zinc deficiency. Hence,
beneficial effectsof zinc supplements in the acute management of
pneumonia arenot to be expected unless the infant or child is zinc
deficient.As has been typical for the reported studies of zinc
administrationused to prevent or treat diarrhea or pneumonia, Bose
et al donot include data on habitual dietary zinc intake or,
indeed,dietary zinc during hospitalization. The mean baseline serumzinc concentration in their study was higher than that in the2
studies they discussed that had positive results , buta wide range
of mean baseline serum or plasma zinc concentrationshas been
reported in studies in which zinc supplements havehad a positive
effect in preventing diarrhea and pneumonia or in treating diarrhea . In the placebo
groups, serum zincwas significantly higher at discharge than at
baseline in all3 studies, which was attributed to a cessation of
the effectsof the acute phase response. The differential between
the studyof Bose et al and
the 2 positive studies was maintained,however, and the mean for the former was well within a normalrange.

The adequacy of dietary zinc varies with age in young childrenin
developing countries, who typically depend on long-term breastfeedingas
well as on the consumption of plant-based complementary foods.Breastfed
infants delivered at term with birth weights appropriatefor
gestational age are likely to have adequate zinc intakesfor at
least the first 4 mo of life. In contrast, it is almostcertain that
dietary zinc intakes in infants >6 mo old indeveloping countries
will fail to meet requirements. The quantityof zinc derived from
breast milk by 6 mo is very limited, andzinc-unfortified,
plant-based complementary foods do not, atleast currently, provide
adequate zinc, which has been categorizedas a "problem
nutrient." The typically low dietary zinc intakeof older
infants suggests that zinc supplements for the treatmentof
pneumonia are more likely to be effective in infants aged>6 mo.
From a nutritional perspective, therefore, an argumentcan be made
for a different subdivision by age than that selectedby Bose at al
and other investigators.

Although the information on the lack of a treatment effect withage
in the study of Bose et al indicates that additional insightsare
unlikely to be gained from a different age-based subdivisionin
their study, the young age of all participants in a recenttrial by
Brooks et al provides a plausible
explanation forthe negative results with zinc supplementation. This
was a well-documentednegative study on the value of short-term zinc
therapy duringthe management of acute diarrhea in infants <6 mo
old. Oneimportant piece of information missing from the report by
Brookset al, however, was the birth weight of the participants.
Low-birth-weightinfants, especially those identified as
small-for-gestationalage, benefit from zinc supplements commencing
early in infancy. Zinc requirements in all low-birth-weight infants
are higherthan those in normal-weight infants, and the infants'
abilityto absorb the needed quantities of zinc appears to be
limited. Hence, if the report by Brooks et al discouraged theuse of zinc
supplements in infants aged <6 mo with diarrhea,it would be
unfortunate if this discouragement extended to thelow-birth-weight
infant.

The significant treatment effect in subgroup analysis of thehot
season that favors the placebo group should be consideredwhen
balancing the potential benefits and risks of zinc supplementation.Although
there are extensive reassuring data about the safetyof zinc
supplements in typical doses of 10–20 mg Zn/d,this is not the first
instance in which zinc supplements havebeen associated with
undesirable negative results. Finally,the study of Bose et al
leaves doubt about the more generalbenefits to be derived from the
routine administration of zincas an adjuvant therapy for pneumonia
in young children in thedeveloping world and, as the authors
conclude, indicates thepriority of the need for additional studies
in representativepopulations.

http://www.ajcn.org/cgi/content/full/83/5/991


Dr Abdul Aziz Awan