Paediatrica Indonesiana

VOLUME 48 November  NUMBER 6

Original Article

The role of zinc supplementation in humoral immune

response to hepatitis B vaccination in infants:
a double-blind randomized placebo-controlled trial
K. Suarca, Hendra S, B. N. P. Arhana, I K. G. Suandi

Abstract
Background 6XERSWLPDO]LQFLQWDNHPD\GHSUHVVWK\PXVIXQFWLRQ
O\PSKRSUROLIHUDWLRQDQG7FHOOGHSHQGHQW%FHOOSUROLIHUDWLRQ
which can impair antibody production. Zinc supplementation can
improve immune function and reduce morbidity.
Objective To assess the effect of zinc supplementation on infants
anti-HBs titer after hepatitis B vaccination.
Methods A double-blind randomized control trial of 66 healthy
LQIDQWVLQ3XVWX'DXK3XUL'HQSDVDU%DUDWZDVFRQGXFWHG6XEMHFWV
were followed from birth to three months of age and were placed
into two treatment groups using block randomization. One group
received zinc supplements with a standard hepatitis B vaccination
S
LQFH WKH V ]LQFV LPSRUWDQFH DV DQ
essential human micronutrient has been
ZHOO NQRZQ ,Q GHYHORSLQJ FRXQWULHV ]LQF
deficiency has been linked to growth delay
and increased morbidity and mortality from infectious
disease due to impaired immune system development
in infants and children. $ERXW  RI ODFWDWLQJ
mothers world-wide are likely to have inadequate zinc
intake.3,Q,QGRQHVLDVSHFLILFDOO\UHVHDUFKHUVIRXQG
WKDW]LQFGHILFLHQF\RFFXULQRIODFWDWLQJPRWKHUV
]LQF JURXS Q  DQG WKH RWKHU JURXS UHFHLYHG SODFHER DQGRIWKHLULQIDQWV4'RUHDIRXQGWKDW
VXSSOHPHQWVZLWKVWDQGDUGKHSDWLWLV%YDFFLQDWLRQSODFHERJURXS clinical symptoms associated with zinc deficiency
Q 7KHVHUXP]LQFOHYHOVZHUHPHDVXUHGDWEDVHOLQHDQGDW
three months. The difference in levels of anti-HBs titer between the
zinc and placebo groups was the primary endpoint of this study.
Results The serum zinc levels were significantly higher in the zinc
RIWHQRFFXUUHGLQEUHDVWIHGLQIDQWVDQGFRPSDUHGWR
LQIDQWV ERUQ DW WHUP V\PSWRPV RFFXUUHG HDUOLHU LQ
preterm infants.
JURXSFRPSDUHGWRWKHSODFHERJURXS3 ZLWKDPHDQ Insufficient dietary zinc intake can lead to
GLIIHUHQFHRIP,8PO&,WR5HJDUGOHVV
RI EDVHOLQH VHUXP ]LQF OHYHOV WKH PHDQ DQWL+%V WLWHUV ZHUH
significantly higher in the zinc group compared to the placebo
JURXS 3   PHDQ GLIIHUHQFH   P,8P/ 
impaired immune function due to depressed thymus
DFWLYLW\FDXVLQJGHFUHDVHGO\PSKRSUROLIHUDWLRQDQG7
O\PSKRF\WHGHYHORSPHQWZKLFKDOVRKDVWKHDIIHFWRI
&,  WR  0XOWLYDULDWH DQDO\VLV VKRZHG WKDW ]LQF decreasing antibodies due to impaired T dependent
supplementation was the only variable that influenced anti-HBs
WLWHUOHYHOV3
Conclusion 5HJDUGOHVV RI WKHLU LQLWLDO ]LQF VHUXP OHYHO LQIDQWV
receiving zinc supplements along with standard hepatitis B
vaccination have significantly higher levels of anti-HBs titers
than infants receiving hepatitis B vaccination without zinc
supplements.[Paediatr Indones. 2008;48:374-80].
Keywords: zinc supplementation, serum zinc level,
hepatitis B vaccination, anti-HBs titer
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374Paediatr Indones, Vol. 48, No. 6, November 2008

 K. Suarca et al: Zinc supplementation in humoral immune response in infants

B-cell activation.6 Zinc supplementation is not only a Definition of variables

treatment for malnourished or zinc deficient children.
,QFKLOGUHQZLWKQRUPDOVHUXP]LQFOHYHOVEXWZKR Zinc status was determined based on serum zinc
are susceptible to zinc deficiency (e.g. infants aged level. Zinc deficiency was defined as a serum zinc
 WR  PRQWKV ZLWK LQDGHTXDWH ]LQF LQWDNH ]LQF
supplementation can also be beneficial.
Vaccination is used to induce the production of
O\PSKRF\WHVDQWLERGLHVDQGPHPRU\FHOOVWKDWDUH
sensitive to a specific antigen. This process can be
disturbed if zinc intake is suboptimal or deficient.8
7KXVHIIRUWVPXVWEHPDGHWRHQVXUHWKDWDWWKHWLPH
RIYDFFLQDWLRQSDWLHQWV]LQFOHYHOVVKRXOGEHDGHTXDWH
WRHQVXUHPD[LPDODQWLERG\SURGXFWLRQDQGSRVVLEO\
longer immune protection.
7RDVVHVVWKHLPPXQHUHVSRQVHWRYDFFLQDWLRQ
DPHDVXUHPHQWIRUDQWLERG\WLWHULVQHHGHG5HFHQWO\
a technique involving Depnasar was developed and
can be used to measure hepatitis B antibody (anti-
HBs) titers. The aim of this study is to investigate
the effect of oral zinc supplementation on antibody
titer after standard hepatitis B (HB) vaccinations in
healthy infants.
Methods
Design and subjects
This was a double-blind randomized placebo-
FRQWUROOHG WULDO FRQGXFWHG EHWZHHQ )HEUXDU\ 
DQG 0D\  (OLJLEOH VXEMHFWV ZHUH UHFUXLWHG
OHYHOJGOLQQHRQDWHVDQGJGOLQ
infants and preschool-aged children. The immune
response to HB vaccination was determined by
measurement of the anti-HBs titer a month after
HB vaccination was completed. HB vaccination was
given according to a standard vaccination protocol
for public health centers. The length of an episode
of diarrhea was measured from the first occurrence
of diarrhea until recovery. The frequency of episodes
of diarrhea was counted as the number of diarrhea
episodes experienced during the study. Subjects
were deemed compliant if the medicines were not
taken less than or equal to seven days on successive
GD\VLQRQHPRQWKRUOHVVWKDQRUHTXDOWRGD\V
on nonsuccesive days in one month. Subjects were
deemed as noncompliant if the medicines were not
taken more than seven days on succesive days in
RQHPRQWKRUPRUHWKDQGD\VRQQRQVXFFHVVLYH
days in one month. The type of oral nutrition the
infant received during the study period was classified
as either exclusive breastfeeding or nonexclusive
breastfeeding.
Data collection
%DVHOLQH FKDUDFWHULVWLFV FOLQLFDO GDWD WLPH RI
+% YDFFLQDWLRQ QXWULWLRQ W\SH EUHDVWIHG YV QRW
consecutively from all healthy babies born at
3XVNHVPDV3HPEDQWX'DXK3XUL'HQSDVDU%DUDWZKR
met the inclusion criteria. The study received ethical
clearance from the Ethics Commitee of Udayana
0HGLFDO6FKRRO6DQJODK+RVSLWDO'HQSDVDU
:H LQFOXGHG DOO EDELHV ZKR ZHUH ERUQ IURP
VSRQWDQHRXVGHOLYHU\DWWHUPDQGZHUHYLJRURXVZLWK
D ELUWK ZHLJKW EHWZHHQ  DQG  JUDP 7KH
EUHDVWIHGHSLVRGHVRIGLDUUKHDERG\ZHLJKWIROORZ
XSODERUDWRU\UHVXOWVDQGVLGHHIIHFWVZHUHFROOHFWHG
from subjects medical charts and were recorded using
a standardized questionnaire.
Sample size
6DPSOHVL]HZDVFDOFXODWHGWRREWDLQDSRZHURI
parents of all subjects also gave informed consent. DWDVLJQLILFDQFHOHYHORI37RREWDLQWKLV
Infants with a major congenital defect or a mother SRZHU DQG OHYHO RI VLJQLILFDQFH ZH ZRXOG QHHG 
ZLWKDFTXLUHGLPPXQHGHILFLHQF\V\QGURPH$,'6
KLVWRU\RIMDXQGLFHRUSRVLWLYH+%V$JWLWHUKLVWRU\
RI LPPXQRVXSSUHVVLYH WKHUDS\ GXULQJ SUHJQDQF\
or a history of blood transfusion in the last three
months were excluded. The subjects were assigned
by means of block randomization to either receive
zinc or placebo.
VXEMHFWVSHUJURXS:HLQWHQGHGWRLGHQWLI\HIIHFWVRI
P,8POGLIIHUHQFHLQDQWL+%VUHVSRQVHEHWZHHQ
the zinc and placebo groups. Due to the absence
RISUHYLRXVGDWDWRGHWHUPLQHWKHSRROHGVWDQGDUG
GHYLDWLRQDSLORWLQYHVWLJDWLRQZDVSHUIRUPHGRQ
samples and a pooled standard deviation for the anti
+%VWLWHURIP,8POZDVREWDLQHG
Paediatr Indones, Vol. 48, No. 6, November 2008375
 K. Suarca et al: Zinc supplementation in humoral immune response in infants

Randomization charts by a health worker during weekly home

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Subjects were allocated using a block randomization +%VWLWHUVDIWHUGD\VRILQWHUYHQWLRQ6XEMHFWVZHUH
method (six patients per block). Assignments were excluded from the study if subject had a severe illness
SODFHGLQFORVHGHQYHORSHVNHSWDWWKH3KDUPDFHXWLFDO UHTXLULQJKRVSLWDOL]DWLRQVXIIHUHGIURPMDXQGLFHRU+%
,QVWDOODWLRQRI6DQJODK+RVSLWDO'HQSDVDUDQGRSHQHG
after the study ended.
Interventions
Oral zinc supplementation or placebo was administered
soon after subjects were allowed oral intake. The
]LQFJURXSUHFHLYHGPJ]LQFVXOIDWHDVDSRZGHU
JLYHQRQFHDGD\IRUWKUHHPRQWKVDQGWKHSODFHER
group received placebo (saccharum lactis) powder
RQFHDGD\IRUWKUHHPRQWKV7KHSDFNDJLQJFRORU
and aroma of the zinc sulfate and placebo powders
were identical. The raw materials were purchased
IURP D SKDUPDFHXWLFDO GLVWULEXWRU LQ -DNDUWD DQG
WKHPDWHULDOVZHUHSDFNDJHGE\WKH3KDUPDFHXWLFDO
Installation of Sanglah Hospital Denpasar. The
packaging of zinc and placebo were coded A or B
ZLWKDNH\ZKLFKZDVHQFORVHGLQDQHQYHORSHDQG
opened after the study was completed. The officer in
FKDUJHUHVHDUFKHUSDWLHQWDQGSDUHQWGLGQRWNQRZ
about the contents of each package. If the subject
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the medicine was re-administered.
Laboratory measurement
An initial blood specimen for baseline serum zinc level
PHDVXUHPHQWZDVFROOHFWHGLQ3XVWX'DXK3XUL$WWKH
HQGRIVWXG\DEORRGVSHFLPHQXVHGWRWHVWVHUXP]LQF
levels and anti-HBs titers was collected during a home
visit. Measurements of serum zinc levels and anti-HBs
WLWHUVZHUHSHUIRUPHGLQWKH3URGLDODERUDWRU\6HUXP
zinc measurements were done using a colorimetric
PHWKRGZLWK=Q5DQGR[DVDUHDJHQW$QWL+%V
LQIHFWLRQGHWHFWHGE\ODERUDWRU\UHVXOWVFRXOGQRW
FRQWLQXHWRWDNHVXSSOHPHQWVRUJLYHEORRGVDPSOHV
FRXOGQRWEHYDFFLQDWHGDVVFKHGXOHGLIWKHLUSDUHQWV
UHIXVHGWRFRQWLQXHWKHVWXG\RULIWKHKRPHDGGUHVV
could not be found during visitation.
Statistical analysis
6WDWLVWLFDODQDO\VLVZDVSHUIRUPHGXVLQJ>LQVHUWVDPH
YHUVLRQDQGSXEOLVKHURIWKHVWDWLVWLFDOSURJUDPXVHG@
7KHVLJQLILFDQFHOHYHOZDVVHWDW31RUPDOLW\
GDWDZHUHWHVWHGXVLQJDQRQSDUDPHWULF.ROPRJRURY
Smirnov test. Independent sample t-tests were used
WRFRPSDUHGLIIHUHQFHVLQ]LQFVHUXPOHYHOVDQWL+%V
WLWHUV ELUWK ZHLJKWV SUHVHQW ZHLJKWV DQG GLDUUKHD
episodes between the two groups. The effects of
JHQGHU]LQFVWDWXVQXWULWLRQYDULHW\DQGFRPSOLDQFH
ZHUH DQDO\]HG XVLQJ D &KLVTXDUH WHVW )LQDOO\ ZH
performed a multivariate analysis (ANCOVA) to
determine if there were any confounding factors that
may have influenced anti-HBs response.
Results
'XULQJWKHVWXG\SHULRGEDELHVZHUHERUQ7KHUH
ZHUHEDELHVZKRVHSDUHQWVDJUHHGWRSDUWLFLSDWH
LQ WKLV VWXG\ DQG  EDELHV ZHUH H[FOXGHG 2I WKH
UHPDLQLQJEDELHVZHUHSODFHGLQWKH]LQFJURXS
and 33 in the placebo group (Figure 1).
The subject characteristics of infants in the zinc
and placebo groups are shown in Table 1. The increase
in body weight was significantly higher in the zinc group
FRPSDUHG WR WKH SODFHER JURXS   JUDP 6'
titer were measured using the Micro particle Enzyme YVWRJUDP6'UHVSHFWLYHO\
Immunoassay (MEIA) method with reagents from PHDQGLIIHUHQFH &,WR
$XVDE$[\P.LW 3$WWKHHQGRIWKHVWXG\EDELHV
were still exclusively breastfed.
Follow-up ,QLWLDOO\WKHUHZHUHIRXUVXEMHFWVWZREDELHVLQ
WKHSODFHERJURXSWZREDELHVLQWKH]LQFJURXSZLWK
,QIRUPDWLRQRQGLDUUKHDRFFXUUHQFHQXWULWLRQW\SH ]LQFGHILFLHQF\%\WKHHQGRIWKHVWXG\HLJKWEDELHV
ERG\ZHLJKW+%YDFFLQDWLRQVFKHGXOHFRPSOLDQFH (seven babies in the placebo group and one baby in
and side effects was recorded in participants medical the zinc group) exhibited zinc deficiency (data not

376Paediatr Indones, Vol. 48, No. 6, November 2008

 K. Suarca et al: Zinc supplementation in humoral immune response in infants

Babies born in Pustu Dauh Puri Puskesmas

II Denpasar Barat during December 2005
-May 2006 period = 342 babies

71 babies
were included
Babies who were excluded:
- 4 babies with maternal history
Randomization of jaundice
66 babies - 1 baby with labiopalatoshcizis
Randomization Block

Zinc (ZnSO4) Placebo

n= 33 n=33

Drop out n = 3
Drop out n =1
(1 blood extraction
(blood extraction
refusal, 2 unknown
refusal)
address)

Final analysis Final analysis

n= 33 n= 33

Figure 1. The study results

Table 1. Subject characteristics we found a significant difference between babies in

Zinc Placebo WKH ]LQF JURXS DQG WKH SODFHER JURXS   6'
Characteristics Group Group JGOYV6'JGOUHVSHFWLYHO\
(n=33) (n=33)
PHDQGLIIHUHQFH JGO&,WR
Sex; male, n(%) 12 (36.4) 17 (51.5)
Birth weight (g); mean (SD) 3106.1 3131.8 3 Figure 2). Because there was an insufficient
Present weight (g); mean (SD) (381.6) (304.9) QXPEHU RI EDELHV ZKR H[KLELWHG ]LQF GHILFLHQF\ D
Age at the time of vaccination 6533.3 5760.6
subgroup analysis was not conducted.
Hepatitis B1 (day), mean (SD) (477.7) (416.8)
Hepatitis B2 (day), mean (SD) 1.3 (0.54) 1.1 (0.77) 5HJDUGOHVVRILQLWLDOVHUXP]LQFOHYHOVE\WKHHQG
Hepatitis B3 (day), mean (SD) 30.0 (1.73) 30.2 (1.73)
Initial zinc level; normal, n(%) 60.4 (2.32) 60.6 (1.71)
The end zinc level; normal, n(%) 31 (93.9) 31 (93.9)
Anti-Hbs production response 32 (97.0) 26 (78.8)
High responder, n(%) 9 (27.3) 1(3.0) 110
Good responder, n(%) 23 (69.7) 9 (27.3)
Mean serum zinc level (mikrogram/mL)

Low responder, n(%) 0 14 (42.4)

Non responder, n(%) 1 (3.0) 9 (15.2)
100
Nutrition; exclusive breastfeeding, n(%) 21 (63.6) 15 (45.5)
Episode of diarrhea (time), mean (SD) 0.3 (0.8) 1.3 (2.0)
Compliance, n(%) 32 (97.0) 29 (87.9)
SD = Standard Deviation; n = sample size 90 P= 0.017

shown). The serum zinc concentration increased in 80 Note :

WKH]LQFJURXSIURP6'JGOWR Initial study
6'  JGO ZKLOH LQ WKH SODFHER JURXS WKH End study
70
FRQFHQWUDWLRQOHYHOZHQWIURP6'JGO Zinc Placebo
DWEDVHOLQHWR6'JGOE\WKHHQGRIWKH Groups

VWXG\:KHQFRPSDULQJLQFUHDVHVLQVHUXP]LQFOHYHOV Figure 2. Mean serum zinc level in the two groups

Paediatr Indones, Vol. 48, No. 6, November 2008377

 K. Suarca et al: Zinc supplementation in humoral immune response in infants

1200 controversial results. In a cohort of patients receiving

UHSHDWHGKHPRGLDO\VLV7XUN14 found that there was
1000
no significant difference in the antibody response
#PVK*$UVKVGT
ON7O.

800 to a multivalent influenza vaccine between patients

receiving zinc supplementation and those receiving
600
SODFHER,QDQRWKHUFRKRUWRIKHPRGLDO\VLVSDWLHQWV
400 p<0.001
researchers found that zinc supplementation did not
lead to an enhanced antibody response after HB
200 revaccination. .DUOVHQ found that zinc increased
0
the intestinal antitoxin immune response in patients
receiving oral cholera toxoid vaccination. A recent
-200
Zinc Placebo study from the United States concluded that zinc
Groups supplementation had no effect on antibody responses
Figure 3.#PVK*$UVKVGTRTQNGCHVGT\KPEUWRRNGOGP
after pneumococcal conjugate vaccination in HIV
tation positive adult patients.16
8VLQJ WKH   DQG  PRQWKV +% YDFFLQDWLRQ
RIWKHVWXG\WKHPHDQDQWL+%VWLWHUVZHUHVLJQLILFDQWO\ VFKHGXOH.XPDUIRXQGWKDWRIVXEMHFWVKDGD
higher in infants in the zinc group compared to those ]HURSURWHFWLYHWLWHUDWIRXUZHHNVDIWHUWKHWKLUG
LQ WKH SODFHER JURXS   P,8PO 6'  GRVH ZLWK D JHRPHWULF PHDQ FRQFHQWUDWLRQ RI 
YV  P,8PO 6'  UHVSHFWLYHO\ PHDQ P,8PO,QRXUVWXG\ZHIRXQGWKDWDIWHUYDFFLQDWLRQ
GLIIHUHQFH P,8PO&, anti-HBs mean titer was significantly higher in the zinc
3Figure 3). JURXSWKDQLQWKHSODFHERJURXS:HZHUHQRWDEOHWR
The associations of several confounding factors compare this result with other studies since there is no
that may have influenced anti-HBs titers are shown in other report regarding the role of zinc supplementation
Table 2. No side effects were reported in this study. in antibody response to vaccination in the first three
months of life. This result strengthens the opinion
that zinc supplementation can increase the humoral
Table 2. The relationship between certain variable and anti HBs LPPXQH UHVSRQVH DIWHU YDFFLQDWLRQ though there
titer
are several reports that zinc supplementation does not
Variable F P
have a significant effect. These prior reports have
Compliance 1.271 0.26
VWXGLHGSUHVFKRRODQGDGXOWSRSXODWLRQVKRZHYHUWKXV
Nutrition 2.682 0.10
subjects in these studies have passed the highest growth
Diarrhea episode 0.047 0.83
acceleration period.8 Zinc deficiency during this time
Initial serum zinc level 1.582 0.21 may delay B lymphocyte responses due to impairment of
Zinc supplementation 29.149 <0.0001 B lymphocyte mitogen and plaque-forming responses.13
F = ANCOVA statistical value; P = probability ,QDGGLWLRQSDVVLYHLPPXQLW\IURPPDWHUQDODQWLERGLHV
GHFUHDVHVLQWKHILUVWVL[PRQWKVRIOLIHVXJJHVWLQJWKDW
early effective intervention for zinc deficiency is needed
Discussion to decrease morbidity in susceptible children.
Bhandari reported that zinc supplementation
3UHYLRXVVWXGLHVKDYHUHSRUWHGWKDW]LQFVXSSOHPHQ has beneficial effects as a preventive measure in children
tation increases nonspecific immune system and with normal serum levels. Zinc supplementation
cellular immune responses.7RRXUNQRZOHGJH reduced mortality and morbidity rate due to various
the role of zinc supplementation in the humoral LQIHFWLRXVGLVHDVHV7KHUHIRUHZHVXJJHVWWKDWIRRGIRU
immune response after vaccination in infants has not babies and preschool children in developing countries
been reported. Several studies have been conducted be fortified with zinc.
looking at the role of zinc supplementation in $W EDVHOLQH ZH IRXQG IRXU LQIDQWV ZLWK ]LQF
the adult humoral immune response; albeit with deficiency in both the zinc and placebo groups. By the

378Paediatr Indones, Vol. 48, No. 6, November 2008

 K. Suarca et al: Zinc supplementation in humoral immune response in infants

HQGRIWKLVVWXG\ZHREVHUYHGRQHLQIDQW]LQFJURXS WKHOLPLWDWLRQVRIWKHDQWLERG\PHDVXUHPHQWWRROQRW

and seven infants (placebo group) with low serum zinc all results could be presented with an absolute number.
levels. Zinc supplementation led to significantly higher 7KHUHIRUHZHWRRNDPD[LPXPDQGPLQLPXPYDOXH
zinc levels in the zinc group compared to the placebo approach if the measurement value result was less than
JURXS3 7KHUHZHUHRIVXEMHFWVZKR
were still breastfed exclusively until the end of this
VWXG\$FURVVVHFWLRQDOVXUYH\LQ:HVW-DYDFRQGXFWHG
by Dijkhuizen4 IRXQG WKDW  RI EDELHV DQG 
of lactating mothers were zinc deficient. Lactating
mothers with low serum zinc levels also have low
]LQFOHYHOVLQWKHLUEUHDVWPLONZKLFKFRQWULEXWHVWR
zinc deficiency in the infants. Since the number
of subjects with zinc deficiency were quite small in
RXUVWXG\ZHFRXOGQRWFRQGXFWDVXEJURXSDQDO\VLV
to compare differences in outcomes between babies
with normal and low serum zinc levels. Several studies
have reported that zinc supplementation can increase
growth and development in infants and children.
 The results of our study corroborate the findings
RIHDUOLHUUHSRUWVDVWKHLQFUHDVHLQERG\ZHLJKWZDV
significantly higher in the zinc group compared to
placebo group.
Side effects with zinc supplementation have
not been reported in most studies. No side
HIIHFWV ZHUH IRXQG LQ RXU VWXG\ HLWKHU WKRXJK VLGH
effects of zinc supplementation may occur at very
high doses. The cause of side effects with zinc
supplementation may be due to the zinc molecules
KLJKDIILQLW\IRUHOHFWURQVZKLFKDUHSUHVHQWLQVHYHUDO
amino acids.13
Four subjects were excluded for reasons un-
related to zinc supplementation. Two babies were
or exceeded the measurement tool capacity.
,Q FRQFOXVLRQ UHJDUGOHVV RI LQLWLDO ]LQF VHUXP
OHYHOVWKHDQWLERG\WLWHULQUHVSRQVHWR+%YDFFLQDWLRQ
in the zinc supplementation group was higher than in
WKHSODFHERJURXS)XUWKHUPRUHLWZDVREVHUYHGWKDW
zinc supplementation at the levels used had no side
effects.
Acknowledgments
0\KLJKHVWJUDWLWXGHJRHVWR,*GH5DND:LGLDQD0'DQG,*XVWL
/DQDQJ6LGLDUWD0'IRUWKHLUKHOSLQFRQVWUXFWLQJPHWKRGRORJ\
and statistical analyses in this study.
References
 2VHQGDUS6-0:HVW&(%ODFN5(7KHQHHGIRUPDWHUQDO
zinc supplementation in developing countries: An unresolved
LVVXH-1XWU66
 2VHQGDUS6-06DQWRVKDP0%ODFN5(:DKHG0$5DDLM
-0$)XFKV*-(IIHFWRI]LQFVXSSOHPHQWDWLRQEHWZHHQDQG
6 mo of life on growth and morbidity of Bangladesh infants
LQXUEDQVOXPV$P-&OLQ1XWU
 &DXOILHOG/(=DYDOHWD16KDQNDU$+0HULDOGL03RWHQWLDO
contribution of maternal zinc supplementation during
SUHJQDQF\WRPDWHUQDODQGFKLOGVXUYLYDO$P-&OLQ1XWU
excluded because parents refused blood tests by the
HQGRIWKHVWXG\DQGWZREDELHVZHUHQRWLQFOXGHG
EHFDXVHWKHLUKRPHDGGUHVVHVZHUHXQNQRZQ7KXV
intention-to-treat analysis was performed on the
final data.
The effect of maternal zinc level on infant
antibody response remains controversial. A study in
Ecuador showed that there was no proof that zinc plays
a role in antibody transfer from mother to her infant.
Others studies suggest that zinc supplementation in
pregnant women might produce a higher antibody titer
in her baby.1 Due to the limitation of resources we did
not measure anti-HBs and HBs-Ag titer for babies and
66
 'LMNKXL]HQ0$:LHULQJD)7:HVW&(0XKHUGL\DQWLQLQJVLK
Muhilal. Concurrent micronutrient deficiencies in lactating
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$QQ5HY1XWU
 .DUOVHQ 7+ 6RPPHUIHOW + .ORPVWDG 6 $QGHUVHQ 3.
6WUDQG7$8OYLN5-et al. Intestinal and systemic immune
responses to an oral cholera toxoid B subunit whole-cell
vaccine administered during zinc supplementation. Infect
mothers at baseline. The antibody production response ,PPXQ
would be clearer if pre- and post-supplementation  6KULPSWRQ 5 *URVV 5 'DUQWRQ+LOO , <RXQJ 0 =LQF
studies or repeated measurements were done. Due to deficiency: what are the most appropriate interventions?

Paediatr Indones, Vol. 48, No. 6, November 2008379

 K. Suarca et al: Zinc supplementation in humoral immune response in infants
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