Oral copper supplementation: effect on copper and zinc balance during acute gastroenteritis in infants13 Car/os
Castillo-Dur#{225}n,
To evaluate
ABSTRACT tation during signed
recovery
from
Vial,
and
the effect acute
Ricardo
of copper
diarrhea,
supplemen-
we randomly
as-
infants to receive either 80 g copper d ‘ or a placebo. Metabolic balance and and zinc concentrations were measured before (period 1) and 6 d after admission (period 2).
kg body
.
plasma
wt’
copper
randomization Fifteen
control
copper
during
supplemented riod 2 but
.
subjects
were
studied
was not affected
period group.
mented
2 rose Copper
after
respiratory
increased for pegroup. Zinc con-
interference
improved over time in both groups in the placebo group for period by copper supplementation on
was noted.
Copper from
supplementation
diarrhea
1990:51:1088-92.
KEY
WORDS
is not
Zinc,
during recommended.
copper,
metabolic
but zinc reten2. A significant zinc absorption
the early phase of Am J C/in
balance,
We hypothesized that by providing extra copper during recovwe could prevent the copper depletion that accompanies diarrheal disease. We were also interested in evaluating the potential interaction ofcopper supplementation on zinc nutrition ery
during
diarrhea,
supplementation
Sixteen
Acute gastroenteritis is a health problem of global importance, especially in developing countries. Despite its high preyalence,
many
aspects
stood.
Information
during
acute
ofits
pathophysiology
on nitrogen
diarrhea
is now
and
are not well
energy
available.
balance
Increased
under-
in infants macronutri-
,
mineral
absorption.
Nutritional zinc and copper deficiencies have been shown to be associated with diarrheal disease (3-5). We (6) previously demonstrated in malnourished children a clear association between a history of diarrheal episodes and low plasma copper and zinc concentrations. In these marasmic infants, copper deficit was more prevalent than was zinc deficiency (6). We (7) also reported significant increases in fecal copper and zinc losses
during
hospitalization.
acute
hospital admission with another study specific tation 1088
diarrheal
Copper
balance
episodes
(7). The present (7),
and new results during the early
extends
in infants
remained
negative
who
require
1 wk
after
study,
these
done in conjunction observations, providing
on the effect oforal stages of recovery
copper supplemenfrom acute diarrhea. Am J C/in Nutr
diarrhea.
to the
infants
aged
Pediatric
3-14
Unit
mo
at the
in Santiago, Chile because of acute were entered into the study. Infants tions, with urinary tract infections, receiving antibiotics were excluded. after
entry
because
of
incomplete on detailed
(6.4 Sotero
± 3.2 mo, del
Rio
i ± SD) Hospital
diarrhea and dehydration, with congenital malformawith suspected sepsis, or Two infants were excluded and unreliable fecal and nursing records obtained as
urine collections based part of the metabolic balance protocol. The 14 study infants received routine treatment consisting ofintravenous hydration during the initial 24-48 h and electrolytes and acid base abnormalities were adjusted according to individual needs; antibiotics were not used. Oral feedings were started 8- 1 2 h after admission by use of reconstituted powdered, whole-fat cow milk wt:vol)
with
added
was started at 50 mL within 1 wk depending
. kg
sucrose ‘ .d
(5%). ‘
and
The
increased
volume
of feeding
up to 1 50 mL/kg
on gastrointestinal tolerance. A 2-d metabolic-balance study was conducted in all infants during the first 48 h after admission (period 1) and on days 6 and 7 (period 2). Seven of the 14 infants in the diarrhea group were randomly assigned to oral copper supplementation at 80 g. kg body wt’ d ‘, as cupric sulfate, after completing bal.
ent losses have been described during the acute stage and during recovery from diarrhea; macronutrient retention normalizes after 6-8 wk of convalescence ( 1 2). Less is known about trace
from
male
admitted
(7%, Introduction
recovery
Subjects and methods
zinc
copper-supplehigher in the
tion was higher
recovery
fecal
only in the was significantly
plasma concentrations to those in the placebo
Nuir
illness.
by supplementation;
significantly retention
infants; were similar
centrations
copper
Uauy
14 hospitalized
sulfate
Fecal
Pablo
l990;5
Downloaded from https://academic.oup.com/ajcn/article-abstract/51/6/1088/4695287 by Denise Hannibal user on 23 May 2018
ance period 1. Copper supplementation was given in two divided doses 30 mm before feedings and was maintained for I wk until the second balance period was completed (period 2). The remaining seven infants received a placebo in a similar fashion.
A control
group
of 1 5 male
infants
comparable
in age,
I From the Institute of Nutrition and Food Technology (INTA), University of Chile, and the Dr S#{243}tero del Rio Hospital, Santiago, Chile, and the Department ofPediatrics and Human Nutrition Center, University ofTexas Southwestern Medical Center, Dallas. 2 Supported in part by CONICYT grant 0 175/84 and United Nations University. 3 Address reprint requests to R Uauy, University of Texas Southwestern Medical Center, Department of Pediatrics, 5323 Harry Hines Boulevard, Dallas, TX 75235-9063. ReceivedMay I, 1989. Accepted for publication August 23, 1989.
1: 1088-92.
Printed
in USA.
© 1990 American
Society
for Clinical
Nutrition
Cu TABLE
SUPPLEMENTATION
IN
ofthe
study
1089
DIARRHEA
TABLE 2 Fecal copper and zinc concentrations
1
Characteristics
ACUTE
groups*
study
during
balance
periods
in the
groups*
Diarrhe a group Diarrhea Copper supplemented
Age(mo) Birth weight (kg) Weight for age (% of
WHO standard)
Placebo
(n=7)
(n=7)
7.0(3-14) 3. 1 (2.2-3.6)
5.9(3-13) 3.5 (2.2-3.7)
79.8
(62-97)
80.8
(61-105)
Days of diarrhea beforeadmission
6
(2-15)
4
(2-15)
Median:
in parentheses.
*
range
Control (n=
Copper
group 15)
7.0(4-12) 3.4(2.7-3.6) 82.4(64-96)
0
Period
1
Period2
birth weight, and nutrition status to the diarrhea patients was also subjected to a 48-h balance study while being fed whole cow-milk formula with 5% added sucrose (Table 1). They were selected from among those recovering from acute respiratory diseases but were asymptomatic at the time of the study, usually 2-3 d before theirdischarge from the hospital. Data forthe control placebo
groups
were
offecal trace mineral Daily urine was tainers given
ofthe
with orally
published
losses collected
in part
added 10% sulfuric acid as a marker to indicate
(10 mL). beginning
48-h stool collection. Heparinized obtained after completion of each
riod
for
both
ful
(7).
diarrhea
Zinc
measurements
before
and
and
and
control
copper
intakes
of formula
after
every
and
losses. Copper and zinc contents were also measured. The infants
study
plastic
con-
Brilliant blue was and completion
blood samples (4 mL) metabolic balance pe-
groups were
intake
feeding
food samples were dried tric acid before analysis.
previous
in acute diarrhea (7). in trace mineral-free
were scribed
in our
as previously estimated
by weighing quantifying
de-
from each
carebottle
miscellaneous
ofrandom samples of formula were weighed daily. Fecal and
to constant weight and Trace mineral content
digested of food,
in niurine,
feces, and plasma were analyzed by atomic-absorption spectrophometry (Perkin-Elmer, Norwalk, CT)(8). Mean dietary copper intakes for the diarrhea groups were 6 tg. kg ‘ . d ‘ for period 1 and 28 zg. kg ‘ d ‘ for period 2; the control group received 50 ; kg ‘ . d ‘ Mean intake values ofzinc were 5 1 and 254 zg. kg . d’ for periods 1 and 2, respectively; the control group received 453 zg . kg ‘ . d Written informed consent was obtained from the parents or legal guardians. The study was previously approved by the Ethics Committee ofthe Institute ofNutrition and Food Technology (INTA), which regulates the participation of human sub.
.
jects
in research
St atistical
.
t Significantly :1:Significantly mented
methods,
was normal, normal.
Statistical
and median
and
significance
1.79
2.62
2.39 ± 0.73 1.10±0.40
2.84 ± 0.69
± 1.4 4.20±l.77t
to explore
the correlations
TABLE
different different p < 0.05.
from values for control group, p < 0.05. from period 2 value for the copper-supple-
3
Daily fecal losses ofcopper the study groups*
and zinc during
Diarrhea
Copper
2
the two balance
periods
in
group
supplemented (n=7)
Control (n=
Placebo (n=7) kg body wt-’
15)
.
48.5±23.Ot
64.2±17.Of
54.6
50. 1 ± 47.0t
± 26.6t
group
28.8±6.7
Fecal zinc
Period
of
1
Period2 *j:
p
Castillo-Dur#{225}n,
To evaluate
ABSTRACT tation during signed
recovery
from
Vial,
and
the effect acute
Ricardo
of copper
diarrhea,
supplemen-
we randomly
as-
infants to receive either 80 g copper d ‘ or a placebo. Metabolic balance and and zinc concentrations were measured before (period 1) and 6 d after admission (period 2).
kg body
.
plasma
wt’
copper
randomization Fifteen
control
copper
during
supplemented riod 2 but
.
subjects
were
studied
was not affected
period group.
mented
2 rose Copper
after
respiratory
increased for pegroup. Zinc con-
interference
improved over time in both groups in the placebo group for period by copper supplementation on
was noted.
Copper from
supplementation
diarrhea
1990:51:1088-92.
KEY
WORDS
is not
Zinc,
during recommended.
copper,
metabolic
but zinc reten2. A significant zinc absorption
the early phase of Am J C/in
balance,
We hypothesized that by providing extra copper during recovwe could prevent the copper depletion that accompanies diarrheal disease. We were also interested in evaluating the potential interaction ofcopper supplementation on zinc nutrition ery
during
diarrhea,
supplementation
Sixteen
Acute gastroenteritis is a health problem of global importance, especially in developing countries. Despite its high preyalence,
many
aspects
stood.
Information
during
acute
ofits
pathophysiology
on nitrogen
diarrhea
is now
and
are not well
energy
available.
balance
Increased
under-
in infants macronutri-
,
mineral
absorption.
Nutritional zinc and copper deficiencies have been shown to be associated with diarrheal disease (3-5). We (6) previously demonstrated in malnourished children a clear association between a history of diarrheal episodes and low plasma copper and zinc concentrations. In these marasmic infants, copper deficit was more prevalent than was zinc deficiency (6). We (7) also reported significant increases in fecal copper and zinc losses
during
hospitalization.
acute
hospital admission with another study specific tation 1088
diarrheal
Copper
balance
episodes
(7). The present (7),
and new results during the early
extends
in infants
remained
negative
who
require
1 wk
after
study,
these
done in conjunction observations, providing
on the effect oforal stages of recovery
copper supplemenfrom acute diarrhea. Am J C/in Nutr
diarrhea.
to the
infants
aged
Pediatric
3-14
Unit
mo
at the
in Santiago, Chile because of acute were entered into the study. Infants tions, with urinary tract infections, receiving antibiotics were excluded. after
entry
because
of
incomplete on detailed
(6.4 Sotero
± 3.2 mo, del
Rio
i ± SD) Hospital
diarrhea and dehydration, with congenital malformawith suspected sepsis, or Two infants were excluded and unreliable fecal and nursing records obtained as
urine collections based part of the metabolic balance protocol. The 14 study infants received routine treatment consisting ofintravenous hydration during the initial 24-48 h and electrolytes and acid base abnormalities were adjusted according to individual needs; antibiotics were not used. Oral feedings were started 8- 1 2 h after admission by use of reconstituted powdered, whole-fat cow milk wt:vol)
with
added
was started at 50 mL within 1 wk depending
. kg
sucrose ‘ .d
(5%). ‘
and
The
increased
volume
of feeding
up to 1 50 mL/kg
on gastrointestinal tolerance. A 2-d metabolic-balance study was conducted in all infants during the first 48 h after admission (period 1) and on days 6 and 7 (period 2). Seven of the 14 infants in the diarrhea group were randomly assigned to oral copper supplementation at 80 g. kg body wt’ d ‘, as cupric sulfate, after completing bal.
ent losses have been described during the acute stage and during recovery from diarrhea; macronutrient retention normalizes after 6-8 wk of convalescence ( 1 2). Less is known about trace
from
male
admitted
(7%, Introduction
recovery
Subjects and methods
zinc
copper-supplehigher in the
tion was higher
recovery
fecal
only in the was significantly
plasma concentrations to those in the placebo
Nuir
illness.
by supplementation;
significantly retention
infants; were similar
centrations
copper
Uauy
14 hospitalized
sulfate
Fecal
Pablo
l990;5
Downloaded from https://academic.oup.com/ajcn/article-abstract/51/6/1088/4695287 by Denise Hannibal user on 23 May 2018
ance period 1. Copper supplementation was given in two divided doses 30 mm before feedings and was maintained for I wk until the second balance period was completed (period 2). The remaining seven infants received a placebo in a similar fashion.
A control
group
of 1 5 male
infants
comparable
in age,
I From the Institute of Nutrition and Food Technology (INTA), University of Chile, and the Dr S#{243}tero del Rio Hospital, Santiago, Chile, and the Department ofPediatrics and Human Nutrition Center, University ofTexas Southwestern Medical Center, Dallas. 2 Supported in part by CONICYT grant 0 175/84 and United Nations University. 3 Address reprint requests to R Uauy, University of Texas Southwestern Medical Center, Department of Pediatrics, 5323 Harry Hines Boulevard, Dallas, TX 75235-9063. ReceivedMay I, 1989. Accepted for publication August 23, 1989.
1: 1088-92.
Printed
in USA.
© 1990 American
Society
for Clinical
Nutrition
Cu TABLE
SUPPLEMENTATION
IN
ofthe
study
1089
DIARRHEA
TABLE 2 Fecal copper and zinc concentrations
1
Characteristics
ACUTE
groups*
study
during
balance
periods
in the
groups*
Diarrhe a group Diarrhea Copper supplemented
Age(mo) Birth weight (kg) Weight for age (% of
WHO standard)
Placebo
(n=7)
(n=7)
7.0(3-14) 3. 1 (2.2-3.6)
5.9(3-13) 3.5 (2.2-3.7)
79.8
(62-97)
80.8
(61-105)
Days of diarrhea beforeadmission
6
(2-15)
4
(2-15)
Median:
in parentheses.
*
range
Control (n=
Copper
group 15)
7.0(4-12) 3.4(2.7-3.6) 82.4(64-96)
0
Period
1
Period2
birth weight, and nutrition status to the diarrhea patients was also subjected to a 48-h balance study while being fed whole cow-milk formula with 5% added sucrose (Table 1). They were selected from among those recovering from acute respiratory diseases but were asymptomatic at the time of the study, usually 2-3 d before theirdischarge from the hospital. Data forthe control placebo
groups
were
offecal trace mineral Daily urine was tainers given
ofthe
with orally
published
losses collected
in part
added 10% sulfuric acid as a marker to indicate
(10 mL). beginning
48-h stool collection. Heparinized obtained after completion of each
riod
for
both
ful
(7).
diarrhea
Zinc
measurements
before
and
and
and
control
copper
intakes
of formula
after
every
and
losses. Copper and zinc contents were also measured. The infants
study
plastic
con-
Brilliant blue was and completion
blood samples (4 mL) metabolic balance pe-
groups were
intake
feeding
food samples were dried tric acid before analysis.
previous
in acute diarrhea (7). in trace mineral-free
were scribed
in our
as previously estimated
by weighing quantifying
de-
from each
carebottle
miscellaneous
ofrandom samples of formula were weighed daily. Fecal and
to constant weight and Trace mineral content
digested of food,
in niurine,
feces, and plasma were analyzed by atomic-absorption spectrophometry (Perkin-Elmer, Norwalk, CT)(8). Mean dietary copper intakes for the diarrhea groups were 6 tg. kg ‘ . d ‘ for period 1 and 28 zg. kg ‘ d ‘ for period 2; the control group received 50 ; kg ‘ . d ‘ Mean intake values ofzinc were 5 1 and 254 zg. kg . d’ for periods 1 and 2, respectively; the control group received 453 zg . kg ‘ . d Written informed consent was obtained from the parents or legal guardians. The study was previously approved by the Ethics Committee ofthe Institute ofNutrition and Food Technology (INTA), which regulates the participation of human sub.
.
jects
in research
St atistical
.
t Significantly :1:Significantly mented
methods,
was normal, normal.
Statistical
and median
and
significance
1.79
2.62
2.39 ± 0.73 1.10±0.40
2.84 ± 0.69
± 1.4 4.20±l.77t
to explore
the correlations
TABLE
different different p < 0.05.
from values for control group, p < 0.05. from period 2 value for the copper-supple-
3
Daily fecal losses ofcopper the study groups*
and zinc during
Diarrhea
Copper
2
the two balance
periods
in
group
supplemented (n=7)
Control (n=
Placebo (n=7) kg body wt-’
15)
.
48.5±23.Ot
64.2±17.Of
54.6
50. 1 ± 47.0t
± 26.6t
group
28.8±6.7
Fecal zinc
Period
of
1
Period2 *j:
p
