Net calcium absorption in premature metabolic balance studies”2 Felix
Bronner,
Bernard
ABSTRAC1’
Net
low-birth-weight
preterm
At birth
the
infants
± 0.2 wk and net
± 2 mg
calcium
been
fed low-birth-weight
.
a mean
evaluated
did
not
age
tested
Ofthe
103
significantly,
did
that in proceeds
not
increase
net
calcium
with
D-regulated
mechanism
1992;56:
not
Subjects
34 re-
the
Ethical
four
with
neither
vitamin
vitamin
D and
D
J C/in
Transcellular
transport,
endocytic
fecal
vitamin calcium
calcium
to involve
two
calcium
transport
transport, route,
plementation Fifty-eight
Nutr
cium
absorption
processes:
D (1), and
movement
In newborn
rats,
is as yet
appears to transcellular
in mammals
a paracellular
regulation
by vitamin
intake,
does
not
has
been
movement appear
that
to be subject
a vitamin
.
Table
of study
and
the
consent
was
ob-
by the
for each
is con-
Except for babies with as needed, all subjects
to acute
D-dependent,
the incubator
maintained
trans-
the vitamin
until
rate for
1 wk.
D-dependent (4),
but
transcellular the
passive
by an endocytically calcium absorption
corn-
component
proportion
the developmental
history
intake ofcalcium
in premature infants and to determine whether processes exist in these individuals, we analyzed 1992:56:1037-44.
milk supplereceived sup-
potassium phosphate. formulas and re-
One-hundred content of293
formula,
infants supple-
milliliters of kJ (70 kcal)
and 3.5 g fat, of triglycerides. Cal-
varied
from
60 to 130
data at birth
and
at
group.
Printed
in USA.
of urine and feces, only male subof their beds permitted placement
ready
conditions tubes, after
separation
ofurine
and
apneic spells and treated with were free of detectable disease
the
of thermal
neutrality.
which
were
well
tolerated.
infants
had
been
growing
stool
(5).
xanthine and were They
were
Studies
were
at a constant
mediated in newborn I From the Department of BioStructure and Function, University of Connecticut Health Center, Farmington, CT: the Department of Neonatology, H#{244}pital E Herriot, Universit#{233}Claude Bernard, F-69437 Lyon Cedex 03, France; and the Department of Pediatrics, University Hospital, B-4000 Liege, Belgium. 2 Address reprint requests to F Bronner, Department of Biostructure and Function, University of Connecticut Health Center, Farmington, CT 06030. Received February 19, 1992. Accepted for publication lune 29, 1992.
down regulation of the satuprocess accounting for the of calcium
and
under
not begun
unexpressed
of a fixed
Nuir
were fed human 23 infants also
1 lists anthropometric
inside
(2, 3).
sorption is modulated by up- and rable process, with the nonsaturable
J C/in
Bernard
calcium gluconate and were fed low-birth-weight
as provided d
I
fed via nasogastric
be complemented route (4); as a result,
To evaluate
healthy
Claude
infants D. Ofthese,
shown
rats can exceed 80% (4). By the time the animal is weaned, the endocytic process has become nonfunctional and the saturable process approaches full expression. From then on, calcium ab-
absorption
103
Protocol
and
.4rn
with infants
intake,
mg . kg the time
D, calcium
calcium
in
parental
ceived vitamin D supplementation. the formula had an average energy
paracellular
vitamin
D supplementation,
centration-dependent
ponent
out
age at birth was 3 1 wk. The studies was approved by the
informed
To facilitate the separation jects were used. The design
Intestinal
carried
University
Written
mentation. Thirty-four mented with vitamin
Introduction
cellular
of the
of Liege.
were
gestational balance
tamed for each ofthe premature infants studied. Eleven were fed banked pasteurized human milk without any
cal-
absorption vitamin
Am
studies
Committees
University
it is concluded
infants calcium with the transcellular,
balance
infants whose for the metabolic
and contained 2 g whey as the major protein which 40% was in the form of medium-chain
KEY WORDS supplementation, endogenous
out during the last 1 5 y in the Hospitals of Liege and Lyon.
and methods
premature protocol
1037-44.
calcium
balances carried of the University
Three-day
vitamin
with
yet expressed.
Senterre
58 had
of whom 1 1 infants in
absorption,
preterm low-birth-weight by a nonsaturable route,
of 103
of 30.9
cium affecting percent absorption significantly. Net calcium absorption was a linear function of intake (40-1 30 mg Ca . kg body wt . d’) with a zero intercept. Because vitamin D supplementation
Jacques
cium metabolic neonatal units
an intake
absorption
supplementation
and
results
3 wk later,
infants,
supplemented
Calcium
differ nor
in 103
58 ± 1% with
.d’.
Rigo,
technique.
gestational
received banked human milk, with vitamin D and calcium;
supplementation
Jacques
balance
kg. When
formulas
supplementation.
subgroups
(± SE)
averaged wtt
Piiiei,
was
by a 72-h
1.43 ± 0.03
kg body
D. The remainder were supplemented
Gui’
absorption
absorption
Ca
Salle,
infants
had
of8O
no
calcium
weighed
their
ceived
Louis
infants:
(4). absorption both types of the data of cal-
© 1992 American
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Society
for Clinical
Nutrition
1037
1038
BRONNER
ET
AL
TABLE I Group characteristics5
Group
1 (human milk, no vitamin D supplement: ii = I 1) 2 (human milk. vitamin D supplement: n = 1 1) 3 (human milk. vitamin D and calcium supplements: n = 23) 4 (low-birth-weight formulas, vitamin D supplement: 11
58)
=
5 (all infants:
n
103)
=
Gestational age at birth
Length
Gestational age at study
uk
tin
d
st’k
g
g
32.6 ± 0.3
43 ± 0.4
18.6 ± 2.0
35.3 ± 0.3
1705 ± 55
1895 ± 77
30.3 ± 0.5
39 ± 0.5
27.5 ± 3.1
34.2 ± 0.5
1355 ± 44
1670 ± 87
30.3 ± 0.4
39 ± 0.5
29.2 ± 1.9
34.5 ± 0.4
1310 ± 38
1700
± 44
30.9 ± 0.3
41 ± 0.3
29.9 ± 1.9
35.2 ± 0.2
1456 ± 45
1927
± 41
30.9 ± 0.2
40 ± 0.3
28.3 ± 1.3
35.0 ± 0.2
1439 ± 30
1846 ± 30
Age at study
Birth weight
Weight
at study
5.±SE.
Milk
intended
for
the
balance
studies
time and sampled for analysis. Milk the amount administered was measured corrected administered mentation.
was
prepared
at one
for the residue in tubing and syringe. Vitamin D was by dropper to the infants who received suppleDaily oral doses ranged from 25 (1000) to 50 sg
(2000 IU) vitamin D from the first week oflife. Fecal specimens were collected as passed for 72 h and kept frozen until analysis. Aliquot at 550
portions
of milk
spectrophotometry Net calcium
(5). absorption
intake
and
fecal
enous
fecal
calcium,
true
amount .
fecal
Because
net calcium
ashed
by atomic-absorption
as the
the
were
latter
difference includes
absorption
the
are
presented
between
the data
were
the indexes
ofcalcium
absorption
up each subgroup one obtains the
figure
3 is such
infants.
The
for the entire
of Figures
1-3
give
by simple
plus
linear
and
minus
t test.
regression
of 103
equations
of the
endog-
slopes
of the five regression
underestimates
by Student’s
infants
between the
As discussed equations
means,
ofthe
population
the
further
equations
in Appendix
represents
the
are also
one
SE.
are not always
Correlations
tion
(7).
reconciled.
equal
net fractional
to the slope
(as in groups
1 , 2, and
listed
A, the slope
ofthe
4) and
disand
in Table
2.
of the regression
absorption.
The question arises why the mean values sorption, calculated from the individual net
was made
as
are plotted as a function of individual graphs displayed in Figures 1 and 2;
a representation legends
in the
considered
regressions drawn through the experimental points in the figures. For ease ofcomparison, the intercepts
(6).
as group
of means
2 summarizes
linear played
ana/i’.si.s
Data
Table
four groups of infants, as well as in all infants, one group. Ifthe individual values ofnet calcium absorption making intakes,
.
Comparison
relevant how
the
of percent absorption
net abvalues,
regression two
values
equacan
be
2
ofcalcium
absorption5
Group
1 (human milk. no vitamin D supplement: a = I 1) 2 (human milk, vitamin D supplement: n = 1 1) 3 (human milk, vitamin D and calcium supplements: n = 23) 4 (low-birth-weight formulas, vitamin D supplement: n = 58) 5 (all infants: n = 103)
Net fractional absorption (slope)
Intercept mg
S
homogenates
for calcium is defined
output.
absorbed
.
Statistical
TABLE Indexes
and
#{176}C for 24 h and analyzed
Results
was given by gavage and with a graduated syringe,
Ca
-
kg’
. d’
-6. 1 ± 13.2
Intake nig
0.55
± 0.22
.
kg’
Net absorbed . d’
tng. kg’
. d’
Percent net absorbed %
59.3 ± 3.0
26.4 ± 2.6
46.7 ± 4.0
7.6 ± 10.9
0.51 ± 0.23
47.9
± 2.4
32.0 ± 2.0
67.2 ± 3.6
0.4 ± 9.4
0.67
± 0.13
75.3 ± 3.1
50.9 ± 2.8
67.7 ± 2.5
0.67 ± 0.12 0.58 ± 0.05
91.4 ± 1.6 79.7 ± 1.9
51.4 ± 1.6 46.6 ± 1.5
56.2 ± 1.5 58.9 ± 1.3
-9.7 ± 10.7 0.8 ± 4.4
SE.
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CALCIUM
ABSORPTION
IN
A
PREMATURE
1039
INFANTS
B
100.
50. 50
.-
C
0 20
40
60
80
100 Calcium
When
intake,
the
numerical
the
corrects
regression
value
regression
equation,
of the
equation).
for an intercept
or positive intercept 1 and 2, its numerical
relating
intercept
value
ofthe
net
3 and 5, the slope. be arrived (if negative,
this
reason,
sorption-intake none of the relatively slopes
I 7% for infants
4).
rable,
error
,
averaged
1 44%
58%,
with
groups,
transcellular
statistically
pathway. from
appears to have proceeded over the range of intakes A statistically intake
is zero,
significant net
absorption
with the
not
on
net
net
ab-
may
arise
and in Appendix can signify the
entire
None zero.
ofthe Therefore,
3, and group
positive
intercept
is negative,
in the intercepts
intercepts
calcium
was
absorption
pathway, indicates
at least that,
when
ie, calcium-endog-
small
intercept
was not ingested is likely to be
of the relationship
net calcium
that
curved, values
groups from
absorption
1 and 4 the negative zero and no functional
be attributed errors
the
to the
ofeach
error
lines
mean
intercept associated
with
with the degree ofcurvature are clustered. In other words, distributed
over
the
absorptive
entire
process
component,
range
of .v values
when
many
increased
intake.
port
This
process
was
the
line
are
individual values are are and
calcium
the
far from a nonintake
is
(or active) cornwill diminish as
up, ultimately approaching a plateau that fractional absorption of the nonsaturable
component (8). Figure (group 4), the percent creased
The
(intake),
values
of a saturable
because
to
from
a regression
associated with downregulation ofthe saturable ponent (6), then overall fractional absorption calcium intake goes corresponds to the
values.
2) result
a function ofhow when individual
consists
and
negative
(Table
likely
intercepts did significance
4 shows net
that absorption
is further
in the largest group did not decrease
indication
in evidence
in this
that
studied with in-
no saturable
trans-
group.
Discussion
of
A, a statistically presence of a satu-
by a nonsaturable studied. negative
if the
and
individual
different
in the stool that below, that quantity
the experimental
fact
The
significantly
enous fecal calcium-appears in the food. As discussed and
iden-
effect
2, 19% for group for
standard
saturable
of the
the
therefore
large
an SE of 9.3%.
differences
below intercept
significant
associated for group
was
functional discussed positive
slopes
need
If the
equa-
a slope
intake
be close to zero. For not differ significantly
degree ofcurvature is less than the extremes of intake.
1-4. As shown in Table 3, another. One reason is the
absorption
absorption
and
calcium
well
negative
regression
treatment
on the
ofgroups from one
Overall
ifa
individual values for the resulting least-
ofzero
of the
be based
standard
group
differ. As significant
analysis
will
for group
If fractional four
the
appropri-
Even
The
When the by the intercept,
functions slopes differ
large (40%
net absorbed.
have an intercept in Table 2.
absorption
procedure
is not zero.
statistically significant, as in groups must be taken into account to obtain
mean
squares relationships tical with that shown
This
that
is not value
tion does this automatically. Figures 1-3 are corrected
For
d1
.
is therefore
of the
or subtracting if positive) to the mean value of net calcium absorbed and dividing by the mean intake. For example, in group 4, 5 1 .4 + 9.7/9 1.4 = 0.67 (ie, a value equal to the slope calculated
calcium
wr1
intercept
the
the correct
kg body
human and (B)
at by adding
ately
.
1
FIG 1 . Net calcium absorption (v) as a function of calcium intake (.v) in 1 1 premature infants fed banked milk and (A) no vitamin D supplements: i’ = -6.1 ± 13.2 (1 ± SE) + 0.55 ± 0.22x F1191 = 6.18 (P 0.05): vitamin D supplements: y 7.6 ± 10.9 + 0.51 ± 0.23x F1191 5.10 (P 0.05).
absorption to intake, is effectively zero, as in groups the calculated mean of net fractional absorption equals When this is not the case, the value of the slope can
by deriving
mg
_i1
between
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
value
for the net fractional
absorption
ofcalcium
reported
here is probably the result ofthe largest single study. In the 103 infants, with a mean gestational age of 35 wk and a mean body weight of 1 .44 kg, net calcium absorption was 58% for an intake that
ranged
from
of8O mg Ca . of 10 premature whose
calcium
phorus reported
kg
40 to
120
d. infants
In an earlier whose age
.
intake
ratio here.
mg
averaged
.
kg
.
53 mg
1) was 66 ± 14%, Boya and Domenech
d
, with
not
. kg
accordingly
advocated
intake
.
d
(calcium-phos-
different from the value ( 10), studying somewhat
older and heavier premature infants, reported sorption values of57%, 55%, and 67%. Although was statistically higher than the other two, Domenech
a mean
study (9) mean absorption at study was 2 1-27 d and
higher
net calcium abthe latter value and Boya and
calcium-phosphorus
BRONNER
1040
ET
AL
A
B
100
V
100007
V
007’
0
0
0 50
0
V
1150.
V
V (1 I
I
I
I
U
20
40
60
80
100
1140
20
Calcium
FIG 2. Net calcium absorption milk and supplements ofvitamin and in (B) 58 premature infants ±0.l2xF1,561
ratios within
as a means the range
hand,
Barltrop
(v) as a function D and calcium: fed low-birth-weight
ofincreasing reported
here
et al ( 1 1), who
exceed
to net
the
absorption
net calcium
page again
calcium (Table
retention, the values fell 2, Fig 3). On the other
term when
derived
true
and
calcium
estimates.
absorption
True
value
absorption
in Figures they used
1-3. true
absorption
must
by the quantity
in low-birth-weight infants 3, page 108) or “premature”
109), report values that
mean agree
(14) summary ofbalance varied from 29% to 65%, in two
breast-fed
birth
weight
Ca#{149} kg
‘d’.
of en-
data indicates with one ofthe babies whose
Ehrenkranz
46Ca as an extrinsic
tag,
fed either formulas
cow milk (Table 4,
net absorption values of52% with those reported in Table
preterm 1 . 1 kg)
wt’
.
80
100
140
120
-
ofcalcium intake (‘c) in (A) 23 premature y = 0.4 ± 9.9 (1 ± SE) + 0.67 ± 0.l3x formulas and supplements ofvitamin
dogenous calcium in the feces (Appendix A). In humans the endogenous fecal calcium tends to equal urinary calcium output ( 12). Greer and Tsang ( 1 3), in their detailed tabulations of calcium absorption formula (Table
mg . kg body
60
infants fed banked human F11211 = 27.2 (P 0.0001): D: i’ = -9.7 ± 10.7 + 0.67
33.1 (P 80%, with calcium intakes between 44
mg
. kg
ofthose
than
the
These
.
. d
reported
values
absorption
here.
reported
They
values
are also
by Hillman
are
clearly
substantially
et al (16),
who
in
higher gave
44Ca
as a single intravenous bolus and 46Ca orally. Measurements of true calcium absorption in seven infants (gestational age at birth 33 wk, birth weight 1 .5 kg) by Hillman et al (16) averaged 44% at 2 wk of age were retested. Endogenous between
and .
1 wk
calcium net
1 7 mg
TABLE 3 Significance of
53%
fecal
true
averaged
and
later,
output
absorption,
kg
.
of the difference
d
for the
when
three
accounts but
of the
for the
it would
103 preterm
in the net fractional
infants
difference
have
to have
infants
studied
absorption
mg
hand, values
infants tested,
Net . fractional
using in pre-
t
value
between
absorption
Group 100.
I (human milk, no vitamin D supplement) 2 (human milk, vitamin D supplement)
90. a
80.
F
70
E
60
D#{234}8 C
302,..-’-’
0
8#{176}
0
50
0
(slope)
0.55
1 and 2
0.12
0.5 1
0
0
3 (human milk, vitamin D and calcium supplements)
0
9_4_.p00000
20 10
0.42
2 and 3 0.47
40 30
1 and 3
0.67
1 and 4
-0.35
2 and 4 -0.38
3 and 4 0
0
20
40
60
Calcium intake,
80 mg . kg body
100 wt’
120
140
. d’
4 (low-birth-weight formulas, vitamin
FIG 3. Net calcium absorption in 103 premature infants: i’ = 0.8 =
(i’) ±
as a function ofcalcium intake (.v) 44 (.i ± SE) + 0.58 ± 0.05x F11,1011
114.7 (P
0.05.
CALCIUM
ABSORPTION
IN
0
08
0
only
U) U)
0
I,’. -
-
-
n0
0
0
0
over
0
C
a)
However,
a wide
0
0-
II, 20
40 Calcium
.
,
60
80
intake
mg
.
I
kg body
and
I
100
120
140
FIG 4. Percent net calcium absorption as a function ofcalcium intake in 58 premature infants fed low-birth-weight formulas and supplements of vitamin D (group 4, Table 2). The net absorption was corrected on the basis ofthe negative intercept in Figure 2, B, as explained in the text. The least-squares equation describing the relationship between percent net absorption (.i’) and intake (x) is ,t’ = 63.6 ± 1 1.4 ( ± SE) + 0.037 ± 0. 12x; the slope is not significantly different from zero. Mean percent net absorption is 67.0 ± 1.4.
for true
reported
absorption
that
to have
equaled
endogenous
range.
fecal
80%.
Barltrop
calcium
the linear,
et al ( 1 1)
averaged
35-45
findings can
the
1-3
endogenous
calcium
excretion
are comparable
in rats
of 35 wk
at the
2.8 this that
as is true for supplementation
fecal
that
several
excretion
in low-birth-weight
infants
( 1 8), reported
endogenous output intake:
.
calcium
output
of 5.6 rng
of 1 .6 rng kg
d
1
‘
.
kg
that
d
I
was
a value
comparable
previously
reported
(9) for preterm infants with adequate 20). Finally, Abrams et al ( 1 8) report 56 ± 16%,
substantially
of
When
>
80%.
lower
converted
than to
ported by Abrams et al (1 8) is 50%, is comparable with the 58% value Thus,
the
values
reported
here
analysis
beliefthat fractional
of individual calcium calcium
Calcium
supplementation
cause a fraction fraction absorbed
ofcalcium by this
concentration
of soluble
take,
in conditions
especially
intake
and vitamin absorption
with
net
Ehrenkranz
absorption,
generally
groups
et a! value the
value
agree
increase
when
Thus,
re-
the errors, 2.
with
most
net
in the literature and sample. However,
contradicts
absolute
increasing
the transcellular
are
the
general
on
very
high
(Appendix here for
A). preterm
of study
indicate
that
from
vitamin
calcium Two
transport. reports in particular
plasma
3%)
exceeds fluids,
calcium
intakes
to increased
infants
with
a mean
that
vitamin
age
D supple-
failure of vitamin However, there
number
of
is
would this
supplein-
of these
infants
receptors
for
1,25-di-
which
according
dramatically in infants
support
D are
D supplementation
help
to
after birth in 32 wk old, upregulate
inference.
of very-low-birth-weight
active
Cooke
infants,
et al
reported
of 1,25-dihydroxycholecaliferol
to maturity, Salle
of 17 premature
birth weight 1.3 kg) plasma concentrations
in Figure
lead
studies. would be that
concentrations Similarly
mentation
why
to 7 1%. Some
D supplementation
related
sorption.
(>
vitamin
50%
the
so that
linearly
that no saturable why the graphs in
will not
indicate
Halloran and DeLuca (25) increases rats, would also increase dramatically
that
,
et al (9) have reported that babies with 30 pg cholecalciferol/d
hydroxycholecalciferol,
study
only positive inter2, Figure 1 B, and ofthe data reported
effect on calcium absorption. And, capacity to respond to vitamin D,
in the current explanation
in their
process
of calcium ingested calcium in the luminal further
net absorption
(26),
has been
saturable
component,
intake
Thus, Senterre of premature
included The easiest
ofa
newborn rats (4, 24), this is readily understandable. that
This
in ref 2 1) as well to be true of the
but
are
unrelated
et a! (27)
found
infants
(gestational
that
a daily
in a near-linear
ab-
supple-
age 3 1 wk; mean
with 37.5 jtg cholecalciferol of 25-hydroxycholecalciferal
dihydroxycholecalciferol
are
to calcium
fashion
raised and for the
their 1,25
next
30
increase
the
d, plateauing and convert
retention
be-
developmentally, as implied above for the expression of vitamin D receptors. For this reason, a firm conclusion as to whether vitamin D supplementation improves calcium absorption in
is transported paracellularly route is independent of the calcium.
3 ± 1
hospitals
which, considering reported in Table
D supplementation of preterm babies. can
the
our
phosphorus intake (19, a true absorption value of the
creased
Urinary
. d’.
from
absorption values that have been reported are, moreover, based on the largest reported the
. kg
ofthe infants in the Abrams et al (18) study was 2% of this value, applied to the current study, would yield an
output mg
fecal
placed
time
reports
the abprocess
was invariant with calcium intake, and increased linearly with intake in the in-
mentation had no significant in the absence ofa developed
beneficial. mentation
which
net absorption-intake
(8), but the was in group On the basis
no saturable
calcium
an endogenous fecal calcium output of 1.0-1.9 mg. kg’ whereas their urinary calcium varied from 1 . I to mg . kg . d 1 (as calculated by Ehrenkranz et a!, 1 5), but value seems excessive. Available data (12; Table 9) indicate
endogenous fecal calcium output represented 7 ± 4% of calcium intake in 1 2 low-birth-weight infants (gestational age at birth 32 wk, age at test 35 wk, birth weight 1 .43 kg). If this percentage were applied to the present study, it would represent a mean
ofthe
here. If the amount solubility of food
intestinal retention The data reported
fecal
existence
fants studied the maximum
urinary
aged I I y. One recent study, using stable-isotope reported that five healthy children aged 3-14 y had
3. The
absorption retention
increasing
route,
process.
therefore, to conclude This would explain
exhibited
remain
absent or already at a the function of net ab-
intercept
4 the percent why calcium
as is true
and
the
here. it seems reasonable process was in evidence.
mg . kg I d I (as calculated by Ehrenkranz et al, 1 5), but this value seems excessive. Available data (1 2; Table 9) indicate that in people procedures,
transcellular
paracellular
function is significantly positive cept in the groups studied here it was not statistically significant.
(23),
should
have been curvilinear, with of the saturable, curvilinear
in Figure when
can and
in the infants studied here, was independent of intake
the active
nonsaturable,
reported
(4),
absorbed
ofabsorption
D, was either were the case,
should the sum
rats
amount
in adults (6; Figure 3, based on data (22; Figure 5.7), but does not appear
be inferred
Figures
as in newborn
absolute
percentage
Therefore,
vs intake function
observed as in rats
. d’
wt’
in the
by vitamin If the latter
sorption sorption
0 a)
yet expressed,
Figure 4 illustrates that absorption of calcium
is regulated maximum.
I)
1041
to an increase
unchanged. net fractional
-
.-
0
50
or not
lead
retained.
0
E
0
INFANTS
downregulated
100
here
PREMATURE
and the lumenal
calcium route
in-
is either
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
preterm when
thereafter. This implies that the capacity to absorb vitamin D to the active metabolite may be regulated
infants in infants
must the
await number
research
to determine
of intestinal
receptors
whether for
and
vitamin
1042
BRONNER
D increases.
However,
supplemented
with
as recommended ready expressed from
such
if banked a modest
by Greer intestinal Even
but
at intakes
time
the animal
is 3
is difficult premature
transport
to know infants.
argue
sorption
whether A high
in favor
is unlikely
most
of the
paracellular
of such
transcellular, infants.
(Fig
that
(4).
because
hy-
1976:57:16-25.
it
also exists in eg, of 80%, paracellular
abtransit
An absorption value with the possibility
in preterm
infants
by a
15. Ehrenkranz RA, Ackerman BA, Nelli CM, Ianghorbani M. Absorption ofcalcium in premature infants as measured with a stable isotope 46Ca extrinsic tag. Pediatr Res 1985:19:178-84. 16. Hillman LS, Tack E, Covell DO, Vieira NE, Yergey AL. Measurement of true calcium absorption in premature infants using intravenous 46Ca and oral 44Ca. Pediatr Res 1988:23:589-94. 17. Abrams SA. Sidbury lB. Muenzer I, Esteban NV, Vieira NE, Yergey AL. Stable isotope measurement of endogenous fecal calcium excretion in children. I Pediatr Gastroenterol and Nutr 1991:12:469-
or a saturable,
is negligibly
small
AL
contents of calcium and phosphorus. Arch Dis Child 1977:52: 41-9. 12. Bronner F. Dynamics and function of calcium. In: Comar CL, Bronner F, eds. Mineral metabolism-an advanced treatise. Vol 2A. New York: Academic Press 1964:341-444. 13. Greer FR, Tsang RC. Calcium, phosphorus, magnesium and vitamin D requirements for the preterm infant. In: Tsang RC, ed. Vitamin and mineral requirements in preterm infants. New York: Dekker, 1985:99- 136. 14. Shaw ICL. Evidence for defective skeletal mineralization in lowbirth weight infants: the absorption of calcium and fat. Pediatrics
calciumAt present
the intestinal
an endocytic
route
for
an endocytic
the saturable,
(6) and
is absorbed
calcium-specific
73.
in these
18. Abrams
SA, Esteban
NV. Vieira NE. Yergey AL. Dual stable isotopic absorption and endogenous fecal excretion in low birth weight infants. Pediatr Res 1991:29:615-8. 19. Pelegano IF, Rowe IC, Carey DE, et al. Simultaneous infusion of calcium and phosphorus in parenteral nutrition for premature infants: use of physiologic calcium/phosphorus ratio. I Pediatr 1989:114:115-9. 20. Chessex P. Pineault M, Brisson G, Delvin EE, Glorieux FH. Role ofthe source ofphosphate salt in improving the mineral balance of parenterally fed low birth weight infants. I Pediatr 1990:1 16:765-
assessment of calcium
In conclusion,
preterm are capable net calcium
all ofthis nonvitamin
infants,
that
increased
intake
in absolute absorption, with Vitamin D supplementation absorption
in the
when
of absorbing absorption
calcium appears D-dependent,
calcium
a route,
4), and
age of 35 wk, calcium; their
implies
to possess
< 3 h (30-32). 2) is consistent
calcium
had albenefit
D, hypercalcemia
developed
20%/h
were 10 ug
in addition to the paraundergoes closure by the
when
has
to exceed
route
milk D. eg,
be at risk
an endocytic route fractional absorption.
time in newborns is probably of 58 ± 1 (i ± SE) (Table that
rats seem
wk old (29),
transcellular
not
.sg vitamin
by which calcium is absorbed route. The endocytic route
specific
would
would
of3O
does not supervene (28). As indicated above, newborn pathway cellular
or formula of vitamin
and Tsang ( 1 3), babies that vitamin D receptors would
supplementation,
percalcemia.
human amount
ET
tested
at a gestational
substantial quantities of averages 58%. Most if not
to be transported by a nonsaturable, presumably paracellular process. This ofcalcium
leads
no change appeared
in fractional absorption. to be of no benefit
infants
studied
to a linear
here.
increase to
B
72.
21
References I . Pansu D. Bellaton C, Bronner F. The effect of calcium intake on the saturable and non-saturable components of duodenal calcium transport. Am I Physiol 198 1:240:G32-7. 2. Schachter D, Rosen SM. Active transport of45Ca by the small intestine and its dependence on vitamin D. Am I Physiol 1959:196:
22.
23. 24.
357-62.
3. Pansu D, Bellaton C. Roche C, Bronner F. Duodenal and ileal calcium absorption in the rat and effects of vitamin D. Am I Physiol
25.
1983:244:G695-700.
4. Pansu D. Bellaton C, Bronner F. Developmental changes in the mechanisms ofduodenal calcium transport in the rat. Am I Physiol
26.
1983:244:G20-6.
5. Senterre I, Salle B. Calcium and phosphorus economy ofthe preterm infant and its interaction with vitamin D and its metabolites. Acta Paediatr Scand Suppl I 983:296:85-92. 6. Bronner F. Calcium absorption. In: Johnson LR, Christensen I, Jacobson ED, Jackson MI, Walsh JH, eds. Physiology of the gastrointestinal tract. Vol 2. New York: Raven Press, 1987;1419-35. 7. Acton IS. Analysis of straight-line data. New York: John Wiley & Sons. Inc. 1959. 8. Bronner F, Pansu D, Stein WD. An analysis of intestinal calcium transport across the rat intestine. Am I Physiol 1986:250:G56l-9. 9. Senterre I, Putet G, Salle B. Rigo I. Effects of vitamin D and phosphorus supplementation on calcium retention in preterm infants fed banked milk. I Pediatr 1983:103:305-7. 10. Moya M, Domenech E. Role of calcium-phosphate ratio of milk formulae on calcium balance in low birth weight infants during the first three days oflife. Pediatr Res 1982:16:675-81. I I . Barltrop D. Mole RH, Sutton A. Absorption and endogenous faecal excretion ofcalcium by low birth weight infants on feeds with varying
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
27.
.
Spencer H. Kramer L, Lesniak M, Debartolo M, Norris C, Osis D. Calcium requirements in humans. Report of original data and a review. Clin Orthop 1984:184:270-80. Bronner F. Gastrointestinal absorption ofcalcium. In: Nordin BEC, ed. Calcium in human biology. London: Springer, 1988;93-123. Duflos C, Pansu D. Bellaton C, Bronner F. Solubility of ingested Ca limits Ca absorption. FASEB I 1992;6:A1945(abstr). Ueng T-H, Golub EE, Bronner F. The effect ofage and 1,25-dihydroxyvitamin D3 treatment on the intestinal calcium-binding protein ofsuckling rats. Arch Biochem Biophys 1979:196:624-30. Halloran BP, DeLuca HF. Appearance of the intestinal cytosolic receptor for 1,25-dihydroxyvitamin D3 during neonatal development in the rat. I Biol Chem 198 1:256:7338-42. Cooke R. Hollis B, Watson D, Werkman 5, Chesney R. Vitamin D and mineral metabolism in the very low birth weight infant receiving 400 IU ofvitamin D. I Pediatr 1990:1 16:423-8. Salle BL, Senterre I, Glorieux FH, Delvin EE, Putet G. Vitamin D metabolism in preterm infants. Biol Neonate 1987;52(suppl l):l 1930.
28. Senterre I, on calcium, parathyroid L, Salle B, New York:
David L, Salle B. Effects of 1,25-dihydroxycholecalciferol phosphorus, and magnesium balance and on circulating hormone and calcitonin in preterm infants. In: Stern Friis-Hansen B, eds. Intensive care in the newborn III. Masson, 1981:1 15-28.
29. Clarke RM, Hardy RN. An analysis ofthe mechanism of cessation of uptake of macromolecular substances by the intestine ofthe young rat (“closure”). I Physiol 1969:204:127-34. 30. Balistreri WF. Anatomic and biochemical ontogeny ofthe gastrointestinal tract and liver. In: Tsang RC, Nichols BL, eds. Nutrition during infancy. Philadelphia: Hanley & Belfus, 1988:48. 31. Weisbroclt NW. Motility ofthe small intestine. In: Johnson LR, ed. Physiology of the gastrointestinal tract. New York: Raven Press, 1987:633.
CALCIUM
ABSORPTION
IN
PREMATURE
.v ‘D)
0)
0)
0)
.
E 0
C 0
0. 0
0. 0
U)
.0
U) .0
C)
0
1043
80
60
E
C
INFANTS
40
20 .
0
Ca intake, FIG 1A. True calcium based on the assumption saturable and nonsaturable process is taken arbitrarily rable process is 0.58/d. as
mg . kg1
Caride VI. Prokop ED. Troncale Fl. Buddoura W. Winchenbach K. McCallum RW. Scintigraphic determination ofsmall intestinal transit time: comparison with the hydrogen breath technique. Gastroenterology 1984:86:714-20.
The tions
purpose
calcium
ofthe
Appendix and
1-3
is to relate to current
to identify
function-intercept,
slope,
tional aspects of the absorption The experimentally derived
the
the regression
equa-
concepts
of intestinal
components
of the
and
plateau-with
va is calcium is the
(in
maximum
ingested per been attained,
unit
mg)
mg.kg1
absorbed
calcium
140
I states that nonsaturable
per
nonsaturable
component.
unit
absorption.
calcium process.
intake. as I 30 mg
>
time
(ie.
v, is calcium of v, when permeability
absorption Note that
Moreover,
itsO
d’
time. Km is the value and B is an apparent
Equation rable and
24
h),
(in mg) has
Vmax/2
constant.
is the sum ofa satuB is the slope of the
equation
1 can
be rewrit-
as
(Vmax
+ v)
A is (Vmax
ab-
large
of true
and
Km
5
the expression when
Vmax,
relatively
small
va is evaluated
the calcium intake, positive intercept.
fol-
component
and this
calcium should is zero.
absorption
ileum
saturable
component
in relation
to large
+ v) approaches at moderate
been
absorption at low at low values ofv, If the intercept in the
as when
calcium
as has
2 indicates
inasmuch
a straight situation
ofintestinal
experimentally, (1)
X vi)/(Km
(Vmas
(2)
+ vi). Equation
equals
IA.
intestinal
+ B(v)
X vi)/(Km
intercept,
Thus
process. ( 1 ) relationship
X vi)/(Km
where ie. the
func-
calcium absorption to calcium intake is shown in Figure This relationship may be represented by an equation ofthe lowing type (2, 3): va
120
100
vaA+B(v))
in Figures
absorption
sorption
80
FIG 3A. True calcium absorption as a function ofcalcium in Figure 2A, but with the added assumption that at intakes Ca . kg . d’. no further absorption occurs.
ten
A
derived
60
Ca intake,
absorption as a function of calcium intake. that absorption is a combined function of a process, as in rats ( 1 ). The Vms,, ofthe saturable as 9 mg . . d . The slope of the nonsatuin Figure 3 of the text.
Vmax
APPENDIX
40
. d1
where 32.
20
values Vmax
This
in rats
values
can
( 1 , 4),
then
one
2A).
for v1,
must
be verified
by measuring
intakes. In this situation, look like that in Fig lA. as is true, for example, (4).
of v,
(Fig
with a significantly with a saturable
absorption. done
A,
v becomes
or high
line results is consistent
that
the for
curve
calcium
conclude
that
no
is present.
1uu
to .
80
‘V
0) 0)
E
.
0)
60
E
0. 0
40
U) .0
(0
60
C 0
C 0 0. 0
80
0)
40
U) .0
20
20
,-“
0
0
U
0
0
4o o o io io ito Ca intake, mg . kg1
160
. d1
FIG 2A. True calcium absorption as a function of calcium intake. shown as if only the slope had been determined experimentally, as in Figure 3. but with an apparent intercept that corresponds to the Vms,, assumed for Figure IA.
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
C
0
4o
o Ca intake,
o mg . kgt
100
120
140
160
. d’
FIG 4A. Theoretical representation of true calcium absorption function of calcium intake on the assumption of a saturable and saturable process acting simultaneously, with no further absorption curringatintakes> 130 mgCa.kg.d.
as a
nonoc-
1044
BRONNER
ET
AL
Over
a very
0)
should
0)
component
.
E
the
C 0
2
made
exists),
in the
up
the curve
for
and
parts:
and
1) the
intake
saturable
component,
which
no
the amount
absorption,
depicting
absorption
nonsaturable
intakes
intestine
intakes, calcium
of three
2) the
of calcium
teaus (Fig 4A). For net calcium
0 U) .0
ofcalcium intestinal
be
(ifit
range
range
between
therefore
solubilized
tO
further that
and
is
is absorbed
5’ a theoretical
3)
calcium
curve
pla-
relating
S
,
to v is drawn in Figure 5A, ie, a small negative intercept that corresponds to the endogenous calcium lost in the stool and a plateau that corresponds to a high calcium intake, ie, where
CO
0 a
z
0
20
40
80
60
100
120
140 160
Ca intake,
mg
.
Net
intestinal
quantity Moreover,
of calcium because
sorption and
absorption,
must
ingested the intestine
equal
endogenous
fecal
vfldO
calcium
negative,
equal
to
vfldO.
typically approximates in the urine. Because in preterm
infants
excretion
. kg
in the
lized,
these which
calcium sponds
circumstances means
absorption, to the
that
the
amount
plateau
at high
feces;
all values
when text,
absorbed
I
d
I),
it is not
calcium
might
v
0,
when
correspond
determined fraction of calcium absorption when all ingested calcium is solubilized.
the
solubility in the lumen has are the practical consequences
not
intakes. be solubiand
that
true corre-
of luminal
sol-
curve relating va to v1 the slope of the curve to the
experimentally
at lower
sulted
increased
calcium. absorption
from
phosphate
Ifthere will
diminished
become from
limiting. the above
intake
leads
consid-
to increases
is no increase in calcium ingestion, decrease. Presumably, this has re-
solubility
in the lumen,
i.e., an effective
decrease in bioavailability; however, the fraction of the solubilized calcium that is absorbed is unchanged and the situation would be as schematized in Figures 4A or 5A. If vitamin D has an effect, in Figure 2A. Because ofthe saturable,
vitamin
the situation would be as depicted induction and/or expression of the
D-dependent
transport,
more
calcium
is ab-
sorbed, but this is added to the amount transported by the nonsaturable, paracellular route, as depicted in Figures lA and 2A. The kind of saturation shown in Figures 3A-SA can only result
if intake
increases
one accepts
equation
about
if calcium,
only
1
without
,
saturation
at high
any as
in
calcium
absorption Figures intakes,
simulating this effect, becomes unavailable If calcium were absorbed by a saturable would
transport dence
be definition has
that
become
calcium
see plateauing saturated.
absorption
There proceeds
occurring. 3A-5A
If come
or in situations
for absorption. process only,
at intakes
at which
is no experimental only
can
by a saturable
then the eviroute.
that
does
not
Suppose
in total fecal net calcium
one
lost small
surprising
a limit limit
in Si is
vfldO in humans
vF will be high
to approach
The theoretical In this situation, should
and
the amount of calcium tends to be relatively
intakes,
va, is likely
ubility has been reached. is shown in Figure 3A. preceding
some
intake,
absorption,
a regression ofS on v, as in the studies reported here, exhibit a statistically significant negative intercept. Let us now consider the situation at very high calcium Under
va,
(3)
in the 3 that
As noted
absorption,
v is calcium
calcium
equation
5 rng
true
absorption,
in quantity this quantity (
the
vfldO
va is true
from
between
vfldO:
v
vF
calcium
calcium
h. It is clear
between excretion,
-
output,
endogenous
is
mg/24
v
=
difference
and that excreted in the feces. does not store calcium, net ab-
calcium
S, is net intestinal
is
is the
the difference
fecal Si
where
S,.
calcium What erations?
kg1 . d1
FIG 5A. Representation ofthe relationship between net calcium absorption and calcium intake. The negative intercept (exaggerated for ready visualization) represents the quantity ofendogenous fecal calcium excreted under conditions ofzero calcium intake.
vF
wide
the relationship
‘0
intakes,
ie,
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
References 1 . Pansu D, Bellaton C. Bronner F. The effect of calcium intake on the saturable and non-saturable components of duodenal calcium transport. Am I Physiol 198 1;240:G32-7. 2. Bronner F. Calcium absorption. In: Johnson LR, Christensen J, Jacobson ED, Jackson MI, Walsh IH, eds. Vol 2. New York: Raven Press, 1987:1419-35.
3. Bronner
F, Pansu D, Stein WD. An analysis of calcium transport the rat intestine. Am I Physiol 1986:250:0561-9. 4. Pansu D, Bellaton C, Roche C, Bronner F. Duodenal and ileal calcium absorption in the rat and effects of vitamin D. Am I Physiol across
1983:244:0695-700.
Bronner,
Bernard
ABSTRAC1’
Net
low-birth-weight
preterm
At birth
the
infants
± 0.2 wk and net
± 2 mg
calcium
been
fed low-birth-weight
.
a mean
evaluated
did
not
age
tested
Ofthe
103
significantly,
did
that in proceeds
not
increase
net
calcium
with
D-regulated
mechanism
1992;56:
not
Subjects
34 re-
the
Ethical
four
with
neither
vitamin
vitamin
D and
D
J C/in
Transcellular
transport,
endocytic
fecal
vitamin calcium
calcium
to involve
two
calcium
transport
transport, route,
plementation Fifty-eight
Nutr
cium
absorption
processes:
D (1), and
movement
In newborn
rats,
is as yet
appears to transcellular
in mammals
a paracellular
regulation
by vitamin
intake,
does
not
has
been
movement appear
that
to be subject
a vitamin
.
Table
of study
and
the
consent
was
ob-
by the
for each
is con-
Except for babies with as needed, all subjects
to acute
D-dependent,
the incubator
maintained
trans-
the vitamin
until
rate for
1 wk.
D-dependent (4),
but
transcellular the
passive
by an endocytically calcium absorption
corn-
component
proportion
the developmental
history
intake ofcalcium
in premature infants and to determine whether processes exist in these individuals, we analyzed 1992:56:1037-44.
milk supplereceived sup-
potassium phosphate. formulas and re-
One-hundred content of293
formula,
infants supple-
milliliters of kJ (70 kcal)
and 3.5 g fat, of triglycerides. Cal-
varied
from
60 to 130
data at birth
and
at
group.
Printed
in USA.
of urine and feces, only male subof their beds permitted placement
ready
conditions tubes, after
separation
ofurine
and
apneic spells and treated with were free of detectable disease
the
of thermal
neutrality.
which
were
well
tolerated.
infants
had
been
growing
stool
(5).
xanthine and were They
were
Studies
were
at a constant
mediated in newborn I From the Department of BioStructure and Function, University of Connecticut Health Center, Farmington, CT: the Department of Neonatology, H#{244}pital E Herriot, Universit#{233}Claude Bernard, F-69437 Lyon Cedex 03, France; and the Department of Pediatrics, University Hospital, B-4000 Liege, Belgium. 2 Address reprint requests to F Bronner, Department of Biostructure and Function, University of Connecticut Health Center, Farmington, CT 06030. Received February 19, 1992. Accepted for publication lune 29, 1992.
down regulation of the satuprocess accounting for the of calcium
and
under
not begun
unexpressed
of a fixed
Nuir
were fed human 23 infants also
1 lists anthropometric
inside
(2, 3).
sorption is modulated by up- and rable process, with the nonsaturable
J C/in
Bernard
calcium gluconate and were fed low-birth-weight
as provided d
I
fed via nasogastric
be complemented route (4); as a result,
To evaluate
healthy
Claude
infants D. Ofthese,
shown
rats can exceed 80% (4). By the time the animal is weaned, the endocytic process has become nonfunctional and the saturable process approaches full expression. From then on, calcium ab-
absorption
103
Protocol
and
.4rn
with infants
intake,
mg . kg the time
D, calcium
calcium
in
parental
ceived vitamin D supplementation. the formula had an average energy
paracellular
vitamin
D supplementation,
centration-dependent
ponent
out
age at birth was 3 1 wk. The studies was approved by the
informed
To facilitate the separation jects were used. The design
Intestinal
carried
University
Written
mentation. Thirty-four mented with vitamin
Introduction
cellular
of the
of Liege.
were
gestational balance
tamed for each ofthe premature infants studied. Eleven were fed banked pasteurized human milk without any
cal-
absorption vitamin
Am
studies
Committees
University
it is concluded
infants calcium with the transcellular,
balance
infants whose for the metabolic
and contained 2 g whey as the major protein which 40% was in the form of medium-chain
KEY WORDS supplementation, endogenous
out during the last 1 5 y in the Hospitals of Liege and Lyon.
and methods
premature protocol
1037-44.
calcium
balances carried of the University
Three-day
vitamin
with
yet expressed.
Senterre
58 had
of whom 1 1 infants in
absorption,
preterm low-birth-weight by a nonsaturable route,
of 103
of 30.9
cium affecting percent absorption significantly. Net calcium absorption was a linear function of intake (40-1 30 mg Ca . kg body wt . d’) with a zero intercept. Because vitamin D supplementation
Jacques
cium metabolic neonatal units
an intake
absorption
supplementation
and
results
3 wk later,
infants,
supplemented
Calcium
differ nor
in 103
58 ± 1% with
.d’.
Rigo,
technique.
gestational
received banked human milk, with vitamin D and calcium;
supplementation
Jacques
balance
kg. When
formulas
supplementation.
subgroups
(± SE)
averaged wtt
Piiiei,
was
by a 72-h
1.43 ± 0.03
kg body
D. The remainder were supplemented
Gui’
absorption
absorption
Ca
Salle,
infants
had
of8O
no
calcium
weighed
their
ceived
Louis
infants:
(4). absorption both types of the data of cal-
© 1992 American
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
Society
for Clinical
Nutrition
1037
1038
BRONNER
ET
AL
TABLE I Group characteristics5
Group
1 (human milk, no vitamin D supplement: ii = I 1) 2 (human milk. vitamin D supplement: n = 1 1) 3 (human milk. vitamin D and calcium supplements: n = 23) 4 (low-birth-weight formulas, vitamin D supplement: 11
58)
=
5 (all infants:
n
103)
=
Gestational age at birth
Length
Gestational age at study
uk
tin
d
st’k
g
g
32.6 ± 0.3
43 ± 0.4
18.6 ± 2.0
35.3 ± 0.3
1705 ± 55
1895 ± 77
30.3 ± 0.5
39 ± 0.5
27.5 ± 3.1
34.2 ± 0.5
1355 ± 44
1670 ± 87
30.3 ± 0.4
39 ± 0.5
29.2 ± 1.9
34.5 ± 0.4
1310 ± 38
1700
± 44
30.9 ± 0.3
41 ± 0.3
29.9 ± 1.9
35.2 ± 0.2
1456 ± 45
1927
± 41
30.9 ± 0.2
40 ± 0.3
28.3 ± 1.3
35.0 ± 0.2
1439 ± 30
1846 ± 30
Age at study
Birth weight
Weight
at study
5.±SE.
Milk
intended
for
the
balance
studies
time and sampled for analysis. Milk the amount administered was measured corrected administered mentation.
was
prepared
at one
for the residue in tubing and syringe. Vitamin D was by dropper to the infants who received suppleDaily oral doses ranged from 25 (1000) to 50 sg
(2000 IU) vitamin D from the first week oflife. Fecal specimens were collected as passed for 72 h and kept frozen until analysis. Aliquot at 550
portions
of milk
spectrophotometry Net calcium
(5). absorption
intake
and
fecal
enous
fecal
calcium,
true
amount .
fecal
Because
net calcium
ashed
by atomic-absorption
as the
the
were
latter
difference includes
absorption
the
are
presented
between
the data
were
the indexes
ofcalcium
absorption
up each subgroup one obtains the
figure
3 is such
infants.
The
for the entire
of Figures
1-3
give
by simple
plus
linear
and
minus
t test.
regression
of 103
equations
of the
endog-
slopes
of the five regression
underestimates
by Student’s
infants
between the
As discussed equations
means,
ofthe
population
the
further
equations
in Appendix
represents
the
are also
one
SE.
are not always
Correlations
tion
(7).
reconciled.
equal
net fractional
to the slope
(as in groups
1 , 2, and
listed
A, the slope
ofthe
4) and
disand
in Table
2.
of the regression
absorption.
The question arises why the mean values sorption, calculated from the individual net
was made
as
are plotted as a function of individual graphs displayed in Figures 1 and 2;
a representation legends
in the
considered
regressions drawn through the experimental points in the figures. For ease ofcomparison, the intercepts
(6).
as group
of means
2 summarizes
linear played
ana/i’.si.s
Data
Table
four groups of infants, as well as in all infants, one group. Ifthe individual values ofnet calcium absorption making intakes,
.
Comparison
relevant how
the
of percent absorption
net abvalues,
regression two
values
equacan
be
2
ofcalcium
absorption5
Group
1 (human milk. no vitamin D supplement: a = I 1) 2 (human milk, vitamin D supplement: n = 1 1) 3 (human milk, vitamin D and calcium supplements: n = 23) 4 (low-birth-weight formulas, vitamin D supplement: n = 58) 5 (all infants: n = 103)
Net fractional absorption (slope)
Intercept mg
S
homogenates
for calcium is defined
output.
absorbed
.
Statistical
TABLE Indexes
and
#{176}C for 24 h and analyzed
Results
was given by gavage and with a graduated syringe,
Ca
-
kg’
. d’
-6. 1 ± 13.2
Intake nig
0.55
± 0.22
.
kg’
Net absorbed . d’
tng. kg’
. d’
Percent net absorbed %
59.3 ± 3.0
26.4 ± 2.6
46.7 ± 4.0
7.6 ± 10.9
0.51 ± 0.23
47.9
± 2.4
32.0 ± 2.0
67.2 ± 3.6
0.4 ± 9.4
0.67
± 0.13
75.3 ± 3.1
50.9 ± 2.8
67.7 ± 2.5
0.67 ± 0.12 0.58 ± 0.05
91.4 ± 1.6 79.7 ± 1.9
51.4 ± 1.6 46.6 ± 1.5
56.2 ± 1.5 58.9 ± 1.3
-9.7 ± 10.7 0.8 ± 4.4
SE.
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
CALCIUM
ABSORPTION
IN
A
PREMATURE
1039
INFANTS
B
100.
50. 50
.-
C
0 20
40
60
80
100 Calcium
When
intake,
the
numerical
the
corrects
regression
value
regression
equation,
of the
equation).
for an intercept
or positive intercept 1 and 2, its numerical
relating
intercept
value
ofthe
net
3 and 5, the slope. be arrived (if negative,
this
reason,
sorption-intake none of the relatively slopes
I 7% for infants
4).
rable,
error
,
averaged
1 44%
58%,
with
groups,
transcellular
statistically
pathway. from
appears to have proceeded over the range of intakes A statistically intake
is zero,
significant net
absorption
with the
not
on
net
net
ab-
may
arise
and in Appendix can signify the
entire
None zero.
ofthe Therefore,
3, and group
positive
intercept
is negative,
in the intercepts
intercepts
calcium
was
absorption
pathway, indicates
at least that,
when
ie, calcium-endog-
small
intercept
was not ingested is likely to be
of the relationship
net calcium
that
curved, values
groups from
absorption
1 and 4 the negative zero and no functional
be attributed errors
the
to the
ofeach
error
lines
mean
intercept associated
with
with the degree ofcurvature are clustered. In other words, distributed
over
the
absorptive
entire
process
component,
range
of .v values
when
many
increased
intake.
port
This
process
was
the
line
are
individual values are are and
calcium
the
far from a nonintake
is
(or active) cornwill diminish as
up, ultimately approaching a plateau that fractional absorption of the nonsaturable
component (8). Figure (group 4), the percent creased
The
(intake),
values
of a saturable
because
to
from
a regression
associated with downregulation ofthe saturable ponent (6), then overall fractional absorption calcium intake goes corresponds to the
values.
2) result
a function ofhow when individual
consists
and
negative
(Table
likely
intercepts did significance
4 shows net
that absorption
is further
in the largest group did not decrease
indication
in evidence
in this
that
studied with in-
no saturable
trans-
group.
Discussion
of
A, a statistically presence of a satu-
by a nonsaturable studied. negative
if the
and
individual
different
in the stool that below, that quantity
the experimental
fact
The
significantly
enous fecal calcium-appears in the food. As discussed and
iden-
effect
2, 19% for group for
standard
saturable
of the
the
therefore
large
an SE of 9.3%.
differences
below intercept
significant
associated for group
was
functional discussed positive
slopes
need
If the
equa-
a slope
intake
be close to zero. For not differ significantly
degree ofcurvature is less than the extremes of intake.
1-4. As shown in Table 3, another. One reason is the
absorption
absorption
and
calcium
well
negative
regression
treatment
on the
ofgroups from one
Overall
ifa
individual values for the resulting least-
ofzero
of the
be based
standard
group
differ. As significant
analysis
will
for group
If fractional four
the
appropri-
Even
The
When the by the intercept,
functions slopes differ
large (40%
net absorbed.
have an intercept in Table 2.
absorption
procedure
is not zero.
statistically significant, as in groups must be taken into account to obtain
mean
squares relationships tical with that shown
This
that
is not value
tion does this automatically. Figures 1-3 are corrected
For
d1
.
is therefore
of the
or subtracting if positive) to the mean value of net calcium absorbed and dividing by the mean intake. For example, in group 4, 5 1 .4 + 9.7/9 1.4 = 0.67 (ie, a value equal to the slope calculated
calcium
wr1
intercept
the
the correct
kg body
human and (B)
at by adding
ately
.
1
FIG 1 . Net calcium absorption (v) as a function of calcium intake (.v) in 1 1 premature infants fed banked milk and (A) no vitamin D supplements: i’ = -6.1 ± 13.2 (1 ± SE) + 0.55 ± 0.22x F1191 = 6.18 (P 0.05): vitamin D supplements: y 7.6 ± 10.9 + 0.51 ± 0.23x F1191 5.10 (P 0.05).
absorption to intake, is effectively zero, as in groups the calculated mean of net fractional absorption equals When this is not the case, the value of the slope can
by deriving
mg
_i1
between
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
value
for the net fractional
absorption
ofcalcium
reported
here is probably the result ofthe largest single study. In the 103 infants, with a mean gestational age of 35 wk and a mean body weight of 1 .44 kg, net calcium absorption was 58% for an intake that
ranged
from
of8O mg Ca . of 10 premature whose
calcium
phorus reported
kg
40 to
120
d. infants
In an earlier whose age
.
intake
ratio here.
mg
averaged
.
kg
.
53 mg
1) was 66 ± 14%, Boya and Domenech
d
, with
not
. kg
accordingly
advocated
intake
.
d
(calcium-phos-
different from the value ( 10), studying somewhat
older and heavier premature infants, reported sorption values of57%, 55%, and 67%. Although was statistically higher than the other two, Domenech
a mean
study (9) mean absorption at study was 2 1-27 d and
higher
net calcium abthe latter value and Boya and
calcium-phosphorus
BRONNER
1040
ET
AL
A
B
100
V
100007
V
007’
0
0
0 50
0
V
1150.
V
V (1 I
I
I
I
U
20
40
60
80
100
1140
20
Calcium
FIG 2. Net calcium absorption milk and supplements ofvitamin and in (B) 58 premature infants ±0.l2xF1,561
ratios within
as a means the range
hand,
Barltrop
(v) as a function D and calcium: fed low-birth-weight
ofincreasing reported
here
et al ( 1 1), who
exceed
to net
the
absorption
net calcium
page again
calcium (Table
retention, the values fell 2, Fig 3). On the other
term when
derived
true
and
calcium
estimates.
absorption
True
value
absorption
in Figures they used
1-3. true
absorption
must
by the quantity
in low-birth-weight infants 3, page 108) or “premature”
109), report values that
mean agree
(14) summary ofbalance varied from 29% to 65%, in two
breast-fed
birth
weight
Ca#{149} kg
‘d’.
of en-
data indicates with one ofthe babies whose
Ehrenkranz
46Ca as an extrinsic
tag,
fed either formulas
cow milk (Table 4,
net absorption values of52% with those reported in Table
preterm 1 . 1 kg)
wt’
.
80
100
140
120
-
ofcalcium intake (‘c) in (A) 23 premature y = 0.4 ± 9.9 (1 ± SE) + 0.67 ± 0.l3x formulas and supplements ofvitamin
dogenous calcium in the feces (Appendix A). In humans the endogenous fecal calcium tends to equal urinary calcium output ( 12). Greer and Tsang ( 1 3), in their detailed tabulations of calcium absorption formula (Table
mg . kg body
60
infants fed banked human F11211 = 27.2 (P 0.0001): D: i’ = -9.7 ± 10.7 + 0.67
33.1 (P 80%, with calcium intakes between 44
mg
. kg
ofthose
than
the
These
.
. d
reported
values
absorption
here.
reported
They
values
are also
by Hillman
are
clearly
substantially
et al (16),
who
in
higher gave
44Ca
as a single intravenous bolus and 46Ca orally. Measurements of true calcium absorption in seven infants (gestational age at birth 33 wk, birth weight 1 .5 kg) by Hillman et al (16) averaged 44% at 2 wk of age were retested. Endogenous between
and .
1 wk
calcium net
1 7 mg
TABLE 3 Significance of
53%
fecal
true
averaged
and
later,
output
absorption,
kg
.
of the difference
d
for the
when
three
accounts but
of the
for the
it would
103 preterm
in the net fractional
infants
difference
have
to have
infants
studied
absorption
mg
hand, values
infants tested,
Net . fractional
using in pre-
t
value
between
absorption
Group 100.
I (human milk, no vitamin D supplement) 2 (human milk, vitamin D supplement)
90. a
80.
F
70
E
60
D#{234}8 C
302,..-’-’
0
8#{176}
0
50
0
(slope)
0.55
1 and 2
0.12
0.5 1
0
0
3 (human milk, vitamin D and calcium supplements)
0
9_4_.p00000
20 10
0.42
2 and 3 0.47
40 30
1 and 3
0.67
1 and 4
-0.35
2 and 4 -0.38
3 and 4 0
0
20
40
60
Calcium intake,
80 mg . kg body
100 wt’
120
140
. d’
4 (low-birth-weight formulas, vitamin
FIG 3. Net calcium absorption in 103 premature infants: i’ = 0.8 =
(i’) ±
as a function ofcalcium intake (.v) 44 (.i ± SE) + 0.58 ± 0.05x F11,1011
114.7 (P
0.05.
CALCIUM
ABSORPTION
IN
0
08
0
only
U) U)
0
I,’. -
-
-
n0
0
0
0
over
0
C
a)
However,
a wide
0
0-
II, 20
40 Calcium
.
,
60
80
intake
mg
.
I
kg body
and
I
100
120
140
FIG 4. Percent net calcium absorption as a function ofcalcium intake in 58 premature infants fed low-birth-weight formulas and supplements of vitamin D (group 4, Table 2). The net absorption was corrected on the basis ofthe negative intercept in Figure 2, B, as explained in the text. The least-squares equation describing the relationship between percent net absorption (.i’) and intake (x) is ,t’ = 63.6 ± 1 1.4 ( ± SE) + 0.037 ± 0. 12x; the slope is not significantly different from zero. Mean percent net absorption is 67.0 ± 1.4.
for true
reported
absorption
that
to have
equaled
endogenous
range.
fecal
80%.
Barltrop
calcium
the linear,
et al ( 1 1)
averaged
35-45
findings can
the
1-3
endogenous
calcium
excretion
are comparable
in rats
of 35 wk
at the
2.8 this that
as is true for supplementation
fecal
that
several
excretion
in low-birth-weight
infants
( 1 8), reported
endogenous output intake:
.
calcium
output
of 5.6 rng
of 1 .6 rng kg
d
1
‘
.
kg
that
d
I
was
a value
comparable
previously
reported
(9) for preterm infants with adequate 20). Finally, Abrams et al ( 1 8) report 56 ± 16%,
substantially
of
When
>
80%.
lower
converted
than to
ported by Abrams et al (1 8) is 50%, is comparable with the 58% value Thus,
the
values
reported
here
analysis
beliefthat fractional
of individual calcium calcium
Calcium
supplementation
cause a fraction fraction absorbed
ofcalcium by this
concentration
of soluble
take,
in conditions
especially
intake
and vitamin absorption
with
net
Ehrenkranz
absorption,
generally
groups
et a! value the
value
agree
increase
when
Thus,
re-
the errors, 2.
with
most
net
in the literature and sample. However,
contradicts
absolute
increasing
the transcellular
are
the
general
on
very
high
(Appendix here for
A). preterm
of study
indicate
that
from
vitamin
calcium Two
transport. reports in particular
plasma
3%)
exceeds fluids,
calcium
intakes
to increased
infants
with
a mean
that
vitamin
age
D supple-
failure of vitamin However, there
number
of
is
would this
supplein-
of these
infants
receptors
for
1,25-di-
which
according
dramatically in infants
support
D are
D supplementation
help
to
after birth in 32 wk old, upregulate
inference.
of very-low-birth-weight
active
Cooke
infants,
et al
reported
of 1,25-dihydroxycholecaliferol
to maturity, Salle
of 17 premature
birth weight 1.3 kg) plasma concentrations
in Figure
lead
studies. would be that
concentrations Similarly
mentation
why
to 7 1%. Some
D supplementation
related
sorption.
(>
vitamin
50%
the
so that
linearly
that no saturable why the graphs in
will not
indicate
Halloran and DeLuca (25) increases rats, would also increase dramatically
that
,
et al (9) have reported that babies with 30 pg cholecalciferol/d
hydroxycholecalciferol,
study
only positive inter2, Figure 1 B, and ofthe data reported
effect on calcium absorption. And, capacity to respond to vitamin D,
in the current explanation
in their
process
of calcium ingested calcium in the luminal further
net absorption
(26),
has been
saturable
component,
intake
Thus, Senterre of premature
included The easiest
ofa
newborn rats (4, 24), this is readily understandable. that
This
in ref 2 1) as well to be true of the
but
are
unrelated
et a! (27)
found
infants
(gestational
that
a daily
in a near-linear
ab-
supple-
age 3 1 wk; mean
with 37.5 jtg cholecalciferol of 25-hydroxycholecalciferal
dihydroxycholecalciferol
are
to calcium
fashion
raised and for the
their 1,25
next
30
increase
the
d, plateauing and convert
retention
be-
developmentally, as implied above for the expression of vitamin D receptors. For this reason, a firm conclusion as to whether vitamin D supplementation improves calcium absorption in
is transported paracellularly route is independent of the calcium.
3 ± 1
hospitals
which, considering reported in Table
D supplementation of preterm babies. can
the
our
phosphorus intake (19, a true absorption value of the
creased
Urinary
. d’.
from
absorption values that have been reported are, moreover, based on the largest reported the
. kg
ofthe infants in the Abrams et al (18) study was 2% of this value, applied to the current study, would yield an
output mg
fecal
placed
time
reports
the abprocess
was invariant with calcium intake, and increased linearly with intake in the in-
mentation had no significant in the absence ofa developed
beneficial. mentation
which
net absorption-intake
(8), but the was in group On the basis
no saturable
calcium
an endogenous fecal calcium output of 1.0-1.9 mg. kg’ whereas their urinary calcium varied from 1 . I to mg . kg . d 1 (as calculated by Ehrenkranz et a!, 1 5), but value seems excessive. Available data (12; Table 9) indicate
endogenous fecal calcium output represented 7 ± 4% of calcium intake in 1 2 low-birth-weight infants (gestational age at birth 32 wk, age at test 35 wk, birth weight 1 .43 kg). If this percentage were applied to the present study, it would represent a mean
ofthe
here. If the amount solubility of food
intestinal retention The data reported
fecal
existence
fants studied the maximum
urinary
aged I I y. One recent study, using stable-isotope reported that five healthy children aged 3-14 y had
3. The
absorption retention
increasing
route,
process.
therefore, to conclude This would explain
exhibited
remain
absent or already at a the function of net ab-
intercept
4 the percent why calcium
as is true
and
the
here. it seems reasonable process was in evidence.
mg . kg I d I (as calculated by Ehrenkranz et al, 1 5), but this value seems excessive. Available data (1 2; Table 9) indicate that in people procedures,
transcellular
paracellular
function is significantly positive cept in the groups studied here it was not statistically significant.
(23),
should
have been curvilinear, with of the saturable, curvilinear
in Figure when
can and
in the infants studied here, was independent of intake
the active
nonsaturable,
reported
(4),
absorbed
ofabsorption
D, was either were the case,
should the sum
rats
amount
in adults (6; Figure 3, based on data (22; Figure 5.7), but does not appear
be inferred
Figures
as in newborn
absolute
percentage
Therefore,
vs intake function
observed as in rats
. d’
wt’
in the
by vitamin If the latter
sorption sorption
0 a)
yet expressed,
Figure 4 illustrates that absorption of calcium
is regulated maximum.
I)
1041
to an increase
unchanged. net fractional
-
.-
0
50
or not
lead
retained.
0
E
0
INFANTS
downregulated
100
here
PREMATURE
and the lumenal
calcium route
in-
is either
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
preterm when
thereafter. This implies that the capacity to absorb vitamin D to the active metabolite may be regulated
infants in infants
must the
await number
research
to determine
of intestinal
receptors
whether for
and
vitamin
1042
BRONNER
D increases.
However,
supplemented
with
as recommended ready expressed from
such
if banked a modest
by Greer intestinal Even
but
at intakes
time
the animal
is 3
is difficult premature
transport
to know infants.
argue
sorption
whether A high
in favor
is unlikely
most
of the
paracellular
of such
transcellular, infants.
(Fig
that
(4).
because
hy-
1976:57:16-25.
it
also exists in eg, of 80%, paracellular
abtransit
An absorption value with the possibility
in preterm
infants
by a
15. Ehrenkranz RA, Ackerman BA, Nelli CM, Ianghorbani M. Absorption ofcalcium in premature infants as measured with a stable isotope 46Ca extrinsic tag. Pediatr Res 1985:19:178-84. 16. Hillman LS, Tack E, Covell DO, Vieira NE, Yergey AL. Measurement of true calcium absorption in premature infants using intravenous 46Ca and oral 44Ca. Pediatr Res 1988:23:589-94. 17. Abrams SA. Sidbury lB. Muenzer I, Esteban NV, Vieira NE, Yergey AL. Stable isotope measurement of endogenous fecal calcium excretion in children. I Pediatr Gastroenterol and Nutr 1991:12:469-
or a saturable,
is negligibly
small
AL
contents of calcium and phosphorus. Arch Dis Child 1977:52: 41-9. 12. Bronner F. Dynamics and function of calcium. In: Comar CL, Bronner F, eds. Mineral metabolism-an advanced treatise. Vol 2A. New York: Academic Press 1964:341-444. 13. Greer FR, Tsang RC. Calcium, phosphorus, magnesium and vitamin D requirements for the preterm infant. In: Tsang RC, ed. Vitamin and mineral requirements in preterm infants. New York: Dekker, 1985:99- 136. 14. Shaw ICL. Evidence for defective skeletal mineralization in lowbirth weight infants: the absorption of calcium and fat. Pediatrics
calciumAt present
the intestinal
an endocytic
route
for
an endocytic
the saturable,
(6) and
is absorbed
calcium-specific
73.
in these
18. Abrams
SA, Esteban
NV. Vieira NE. Yergey AL. Dual stable isotopic absorption and endogenous fecal excretion in low birth weight infants. Pediatr Res 1991:29:615-8. 19. Pelegano IF, Rowe IC, Carey DE, et al. Simultaneous infusion of calcium and phosphorus in parenteral nutrition for premature infants: use of physiologic calcium/phosphorus ratio. I Pediatr 1989:114:115-9. 20. Chessex P. Pineault M, Brisson G, Delvin EE, Glorieux FH. Role ofthe source ofphosphate salt in improving the mineral balance of parenterally fed low birth weight infants. I Pediatr 1990:1 16:765-
assessment of calcium
In conclusion,
preterm are capable net calcium
all ofthis nonvitamin
infants,
that
increased
intake
in absolute absorption, with Vitamin D supplementation absorption
in the
when
of absorbing absorption
calcium appears D-dependent,
calcium
a route,
4), and
age of 35 wk, calcium; their
implies
to possess
< 3 h (30-32). 2) is consistent
calcium
had albenefit
D, hypercalcemia
developed
20%/h
were 10 ug
in addition to the paraundergoes closure by the
when
has
to exceed
route
milk D. eg,
be at risk
an endocytic route fractional absorption.
time in newborns is probably of 58 ± 1 (i ± SE) (Table that
rats seem
wk old (29),
transcellular
not
.sg vitamin
by which calcium is absorbed route. The endocytic route
specific
would
would
of3O
does not supervene (28). As indicated above, newborn pathway cellular
or formula of vitamin
and Tsang ( 1 3), babies that vitamin D receptors would
supplementation,
percalcemia.
human amount
ET
tested
at a gestational
substantial quantities of averages 58%. Most if not
to be transported by a nonsaturable, presumably paracellular process. This ofcalcium
leads
no change appeared
in fractional absorption. to be of no benefit
infants
studied
to a linear
here.
increase to
B
72.
21
References I . Pansu D. Bellaton C, Bronner F. The effect of calcium intake on the saturable and non-saturable components of duodenal calcium transport. Am I Physiol 198 1:240:G32-7. 2. Schachter D, Rosen SM. Active transport of45Ca by the small intestine and its dependence on vitamin D. Am I Physiol 1959:196:
22.
23. 24.
357-62.
3. Pansu D, Bellaton C. Roche C, Bronner F. Duodenal and ileal calcium absorption in the rat and effects of vitamin D. Am I Physiol
25.
1983:244:G695-700.
4. Pansu D. Bellaton C, Bronner F. Developmental changes in the mechanisms ofduodenal calcium transport in the rat. Am I Physiol
26.
1983:244:G20-6.
5. Senterre I, Salle B. Calcium and phosphorus economy ofthe preterm infant and its interaction with vitamin D and its metabolites. Acta Paediatr Scand Suppl I 983:296:85-92. 6. Bronner F. Calcium absorption. In: Johnson LR, Christensen I, Jacobson ED, Jackson MI, Walsh JH, eds. Physiology of the gastrointestinal tract. Vol 2. New York: Raven Press, 1987;1419-35. 7. Acton IS. Analysis of straight-line data. New York: John Wiley & Sons. Inc. 1959. 8. Bronner F, Pansu D, Stein WD. An analysis of intestinal calcium transport across the rat intestine. Am I Physiol 1986:250:G56l-9. 9. Senterre I, Putet G, Salle B. Rigo I. Effects of vitamin D and phosphorus supplementation on calcium retention in preterm infants fed banked milk. I Pediatr 1983:103:305-7. 10. Moya M, Domenech E. Role of calcium-phosphate ratio of milk formulae on calcium balance in low birth weight infants during the first three days oflife. Pediatr Res 1982:16:675-81. I I . Barltrop D. Mole RH, Sutton A. Absorption and endogenous faecal excretion ofcalcium by low birth weight infants on feeds with varying
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27.
.
Spencer H. Kramer L, Lesniak M, Debartolo M, Norris C, Osis D. Calcium requirements in humans. Report of original data and a review. Clin Orthop 1984:184:270-80. Bronner F. Gastrointestinal absorption ofcalcium. In: Nordin BEC, ed. Calcium in human biology. London: Springer, 1988;93-123. Duflos C, Pansu D. Bellaton C, Bronner F. Solubility of ingested Ca limits Ca absorption. FASEB I 1992;6:A1945(abstr). Ueng T-H, Golub EE, Bronner F. The effect ofage and 1,25-dihydroxyvitamin D3 treatment on the intestinal calcium-binding protein ofsuckling rats. Arch Biochem Biophys 1979:196:624-30. Halloran BP, DeLuca HF. Appearance of the intestinal cytosolic receptor for 1,25-dihydroxyvitamin D3 during neonatal development in the rat. I Biol Chem 198 1:256:7338-42. Cooke R. Hollis B, Watson D, Werkman 5, Chesney R. Vitamin D and mineral metabolism in the very low birth weight infant receiving 400 IU ofvitamin D. I Pediatr 1990:1 16:423-8. Salle BL, Senterre I, Glorieux FH, Delvin EE, Putet G. Vitamin D metabolism in preterm infants. Biol Neonate 1987;52(suppl l):l 1930.
28. Senterre I, on calcium, parathyroid L, Salle B, New York:
David L, Salle B. Effects of 1,25-dihydroxycholecalciferol phosphorus, and magnesium balance and on circulating hormone and calcitonin in preterm infants. In: Stern Friis-Hansen B, eds. Intensive care in the newborn III. Masson, 1981:1 15-28.
29. Clarke RM, Hardy RN. An analysis ofthe mechanism of cessation of uptake of macromolecular substances by the intestine ofthe young rat (“closure”). I Physiol 1969:204:127-34. 30. Balistreri WF. Anatomic and biochemical ontogeny ofthe gastrointestinal tract and liver. In: Tsang RC, Nichols BL, eds. Nutrition during infancy. Philadelphia: Hanley & Belfus, 1988:48. 31. Weisbroclt NW. Motility ofthe small intestine. In: Johnson LR, ed. Physiology of the gastrointestinal tract. New York: Raven Press, 1987:633.
CALCIUM
ABSORPTION
IN
PREMATURE
.v ‘D)
0)
0)
0)
.
E 0
C 0
0. 0
0. 0
U)
.0
U) .0
C)
0
1043
80
60
E
C
INFANTS
40
20 .
0
Ca intake, FIG 1A. True calcium based on the assumption saturable and nonsaturable process is taken arbitrarily rable process is 0.58/d. as
mg . kg1
Caride VI. Prokop ED. Troncale Fl. Buddoura W. Winchenbach K. McCallum RW. Scintigraphic determination ofsmall intestinal transit time: comparison with the hydrogen breath technique. Gastroenterology 1984:86:714-20.
The tions
purpose
calcium
ofthe
Appendix and
1-3
is to relate to current
to identify
function-intercept,
slope,
tional aspects of the absorption The experimentally derived
the
the regression
equa-
concepts
of intestinal
components
of the
and
plateau-with
va is calcium is the
(in
maximum
ingested per been attained,
unit
mg)
mg.kg1
absorbed
calcium
140
I states that nonsaturable
per
nonsaturable
component.
unit
absorption.
calcium process.
intake. as I 30 mg
>
time
(ie.
v, is calcium of v, when permeability
absorption Note that
Moreover,
itsO
d’
time. Km is the value and B is an apparent
Equation rable and
24
h),
(in mg) has
Vmax/2
constant.
is the sum ofa satuB is the slope of the
equation
1 can
be rewrit-
as
(Vmax
+ v)
A is (Vmax
ab-
large
of true
and
Km
5
the expression when
Vmax,
relatively
small
va is evaluated
the calcium intake, positive intercept.
fol-
component
and this
calcium should is zero.
absorption
ileum
saturable
component
in relation
to large
+ v) approaches at moderate
been
absorption at low at low values ofv, If the intercept in the
as when
calcium
as has
2 indicates
inasmuch
a straight situation
ofintestinal
experimentally, (1)
X vi)/(Km
(Vmas
(2)
+ vi). Equation
equals
IA.
intestinal
+ B(v)
X vi)/(Km
intercept,
Thus
process. ( 1 ) relationship
X vi)/(Km
where ie. the
func-
calcium absorption to calcium intake is shown in Figure This relationship may be represented by an equation ofthe lowing type (2, 3): va
120
100
vaA+B(v))
in Figures
absorption
sorption
80
FIG 3A. True calcium absorption as a function ofcalcium in Figure 2A, but with the added assumption that at intakes Ca . kg . d’. no further absorption occurs.
ten
A
derived
60
Ca intake,
absorption as a function of calcium intake. that absorption is a combined function of a process, as in rats ( 1 ). The Vms,, ofthe saturable as 9 mg . . d . The slope of the nonsatuin Figure 3 of the text.
Vmax
APPENDIX
40
. d1
where 32.
20
values Vmax
This
in rats
values
can
( 1 , 4),
then
one
2A).
for v1,
must
be verified
by measuring
intakes. In this situation, look like that in Fig lA. as is true, for example, (4).
of v,
(Fig
with a significantly with a saturable
absorption. done
A,
v becomes
or high
line results is consistent
that
the for
curve
calcium
conclude
that
no
is present.
1uu
to .
80
‘V
0) 0)
E
.
0)
60
E
0. 0
40
U) .0
(0
60
C 0
C 0 0. 0
80
0)
40
U) .0
20
20
,-“
0
0
U
0
0
4o o o io io ito Ca intake, mg . kg1
160
. d1
FIG 2A. True calcium absorption as a function of calcium intake. shown as if only the slope had been determined experimentally, as in Figure 3. but with an apparent intercept that corresponds to the Vms,, assumed for Figure IA.
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
C
0
4o
o Ca intake,
o mg . kgt
100
120
140
160
. d’
FIG 4A. Theoretical representation of true calcium absorption function of calcium intake on the assumption of a saturable and saturable process acting simultaneously, with no further absorption curringatintakes> 130 mgCa.kg.d.
as a
nonoc-
1044
BRONNER
ET
AL
Over
a very
0)
should
0)
component
.
E
the
C 0
2
made
exists),
in the
up
the curve
for
and
parts:
and
1) the
intake
saturable
component,
which
no
the amount
absorption,
depicting
absorption
nonsaturable
intakes
intestine
intakes, calcium
of three
2) the
of calcium
teaus (Fig 4A). For net calcium
0 U) .0
ofcalcium intestinal
be
(ifit
range
range
between
therefore
solubilized
tO
further that
and
is
is absorbed
5’ a theoretical
3)
calcium
curve
pla-
relating
S
,
to v is drawn in Figure 5A, ie, a small negative intercept that corresponds to the endogenous calcium lost in the stool and a plateau that corresponds to a high calcium intake, ie, where
CO
0 a
z
0
20
40
80
60
100
120
140 160
Ca intake,
mg
.
Net
intestinal
quantity Moreover,
of calcium because
sorption and
absorption,
must
ingested the intestine
equal
endogenous
fecal
vfldO
calcium
negative,
equal
to
vfldO.
typically approximates in the urine. Because in preterm
infants
excretion
. kg
in the
lized,
these which
calcium sponds
circumstances means
absorption, to the
that
the
amount
plateau
at high
feces;
all values
when text,
absorbed
I
d
I),
it is not
calcium
might
v
0,
when
correspond
determined fraction of calcium absorption when all ingested calcium is solubilized.
the
solubility in the lumen has are the practical consequences
not
intakes. be solubiand
that
true corre-
of luminal
sol-
curve relating va to v1 the slope of the curve to the
experimentally
at lower
sulted
increased
calcium. absorption
from
phosphate
Ifthere will
diminished
become from
limiting. the above
intake
leads
consid-
to increases
is no increase in calcium ingestion, decrease. Presumably, this has re-
solubility
in the lumen,
i.e., an effective
decrease in bioavailability; however, the fraction of the solubilized calcium that is absorbed is unchanged and the situation would be as schematized in Figures 4A or 5A. If vitamin D has an effect, in Figure 2A. Because ofthe saturable,
vitamin
the situation would be as depicted induction and/or expression of the
D-dependent
transport,
more
calcium
is ab-
sorbed, but this is added to the amount transported by the nonsaturable, paracellular route, as depicted in Figures lA and 2A. The kind of saturation shown in Figures 3A-SA can only result
if intake
increases
one accepts
equation
about
if calcium,
only
1
without
,
saturation
at high
any as
in
calcium
absorption Figures intakes,
simulating this effect, becomes unavailable If calcium were absorbed by a saturable would
transport dence
be definition has
that
become
calcium
see plateauing saturated.
absorption
There proceeds
occurring. 3A-5A
If come
or in situations
for absorption. process only,
at intakes
at which
is no experimental only
can
by a saturable
then the eviroute.
that
does
not
Suppose
in total fecal net calcium
one
lost small
surprising
a limit limit
in Si is
vfldO in humans
vF will be high
to approach
The theoretical In this situation, should
and
the amount of calcium tends to be relatively
intakes,
va, is likely
ubility has been reached. is shown in Figure 3A. preceding
some
intake,
absorption,
a regression ofS on v, as in the studies reported here, exhibit a statistically significant negative intercept. Let us now consider the situation at very high calcium Under
va,
(3)
in the 3 that
As noted
absorption,
v is calcium
calcium
equation
5 rng
true
absorption,
in quantity this quantity (
the
vfldO
va is true
from
between
vfldO:
v
vF
calcium
calcium
h. It is clear
between excretion,
-
output,
endogenous
is
mg/24
v
=
difference
and that excreted in the feces. does not store calcium, net ab-
calcium
S, is net intestinal
is
is the
the difference
fecal Si
where
S,.
calcium What erations?
kg1 . d1
FIG 5A. Representation ofthe relationship between net calcium absorption and calcium intake. The negative intercept (exaggerated for ready visualization) represents the quantity ofendogenous fecal calcium excreted under conditions ofzero calcium intake.
vF
wide
the relationship
‘0
intakes,
ie,
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/6/1037/4715503 by University of California School of Law (Boalt Hall) user on 26 July 2018
References 1 . Pansu D, Bellaton C. Bronner F. The effect of calcium intake on the saturable and non-saturable components of duodenal calcium transport. Am I Physiol 198 1;240:G32-7. 2. Bronner F. Calcium absorption. In: Johnson LR, Christensen J, Jacobson ED, Jackson MI, Walsh IH, eds. Vol 2. New York: Raven Press, 1987:1419-35.
3. Bronner
F, Pansu D, Stein WD. An analysis of calcium transport the rat intestine. Am I Physiol 1986:250:0561-9. 4. Pansu D, Bellaton C, Roche C, Bronner F. Duodenal and ileal calcium absorption in the rat and effects of vitamin D. Am I Physiol across
1983:244:0695-700.
