Effects of calcium supplementation and lactation on iron status1–4

Heidi J Kalkwarf and Sonja D Harrast

ABSTRACT Calcium has been shown to inhibit iron of calcium in the supplement (8). Iron status may, therefore, be

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absorption. The consequences of chronic calcium supplementa- compromised by long-term use of calcium supplements or intake
tion on iron status are unclear, however. As part of a randomized of foods high in calcium, particularly in women of reproductive
calcium-supplementation trial in lactating and nonlactating age in whom iron deficiency is common (9).
women in the postpartum period, we determined whether long- The nutritional consequences of long-term calcium supple-
term calcium supplementation and lactation status affected iron mentation in free-living individuals has received little attention.
stores as measured by serum ferritin concentrations. Subjects Yan et al (10) found no effect on serum ferritin concentrations of
(95 lactating and 92 nonlactating) were enrolled at <6 mo post- giving lactating Gambian women (n = 60) a daily dose of 1 g Ca
partum and then randomly assigned to receive either 500 mg Ca as calcium carbonate. However, the supplement was given
as calcium carbonate or a placebo twice daily with meals for 6 between meals so the opportunity for inhibition of iron absorp-
mo. Lactating women weaned their infants <2 mo after enroll- tion was minimized. Sokoll and Dawson-Hughes (11) found no
ment (ie, <8 mo postpartum). Calcium supplementation had no effect on serum ferritin concentrations when healthy pre-
effect on serum ferritin concentrations. At the end of the study, menopausal women (n = 109) were given 250 mg Ca as calcium
geometric mean serum ferritin concentrations were 28.4 mg/L carbonate twice daily with meals for 12 wk.
in the calcium-supplemented group and 27.5 mg/L in the place- As part of a randomized calcium-supplementation trial in lac-
bo group (P > 0.5). Lactation status was significantly related to tating and nonlactating women in the postpartum period, we
serum ferritin concentrations. At baseline, serum ferritin con- determined whether long-term supplementation with 500 mg Ca
centrations were higher in lactating women than in nonlactat- taken twice daily with meals affected iron stores as measured by
ing women (47.7 compared with 31.5 mg/L, P < 0.001). In lac- serum ferritin concentrations. Because of the nature of the study
tating women, serum ferritin concentrations decreased by a population, we also describe the effects of lactation and weaning
mean of 17 mg/L after weaning. By 12 mo postpartum, mean on maternal iron stores. To our knowledge, no reports in the lit-
serum ferritin concentrations in women who were previously erature have specifically evaluated the effects of lactation and
lactating were not significantly higher than those of nonlactat- weaning on maternal iron stores.
ing women (30.5 compared with 25.5 mg/L). These findings
provide reassurance that long-term calcium supplementation
does not impair iron stores. Furthermore, lactation status SUBJECTS AND METHODS
should be considered when assessing iron nutriture of women Study subjects participated in a randomized calcium-supple-
and determinants of iron status in populations. Am J Clin mentation trial in women that was designed to evaluate the effects
Nutr 1998;67:1244–9. of calcium supplementation on changes in bone density postpar-
tum (12, 13). Women were recruited from postpartum hospital
KEY WORDS Lactation, weaning, postpartum period, fer- wards, through newspaper advertisements, and by word of mouth.
ritin, iron stores, iron status, calcium supplementation, calcium Iron status was assessed only in subjects who participated in the
carbonate, randomized trial, women

1
From the Department of Pediatrics, Children’s Hospital Medical Center,
INTRODUCTION Cincinnati.
2
Consumption of calcium supplements has become more com- Presented in part at Experimental Biology ‘97, New Orleans, April 9,
mon as the health and economic consequences of osteoporosis 1997.
3
have come to be better appreciated (1). However, calcium, given Supported in part by grants from the NIH (RO1 AR41366 and MO1
RR08084 from the General Clinical Research Centers Program, National
as a supplement or in the form of dairy products, may reduce
Center for Research Resources).
both heme- and nonheme-iron absorption by 40–60% (2–6). Cal- 4
Address reprint requests to HJ Kalkwarf, Division of General and Com-
cium appears to have the largest effect on iron absorption when munity Pediatrics, Children’s Hospital Medical Center, 3333 Burnet Avenue,
consumed with an iron-containing meal and no effect if con- Cincinnati, OH 45229. E-mail: [email protected].
sumed ≥ 2 h after the meal (7). Consumption of calcium supple- Received August 15, 1997.
ments with meals is recommended to enhance the bioavailability Accepted for publication November 25, 1997.

1244 Am J Clin Nutr 1998;67:1244–9. Printed in USA. © 1998 American Society for Clinical Nutrition
 CALCIUM SUPPLEMENTATION AND IRON STORES 1245

study between <6 and 12 mo postpartum. These women (95 lac- written, informed consent to participate. Of the 187 women who
tating and 92 nonlactating) were enrolled in the study an average enrolled, 158 completed the study successfully. The reasons for
of 5.6 ± 0.8 mo postpartum. Lactating women were breast-feeding subjects being dropped from the study included loss of interest
5.4 ± 1.1 times daily and providing no more than one supplemen- in the study (n = 1), prolonged illness or chronic medication use
tal formula feed per day (111 ± 90 mL) at the time of enrollment. (n = 5), iron supplementation for anemia (n = 1 nonlactating
Lactating women weaned their infants from breast milk in the first woman in the placebo group), use of hormonal contraceptives
2 mo (7 ± 4 wk) after enrollment (ie, <8 mo postpartum). We refer (n = 1), pregnancy (n = 8), not weaning infant within 3 mo (n =
to this group as lactating or previously lactating to reflect their sta- 9), inability to swallow pills (n = 1), and relocation of subject or
tus at the time measurements were obtained. Nonlactating women inability to contact subject (n = 3).
had either fed their infants formula exclusively from birth (n = 86) The effect of calcium supplementation on iron status was
or had breast-fed for ≤ 2 wk (n = 6). determined with repeated-measures analysis of variance, in
Four study groups were created by randomly assigning half of which the primary outcome variable was serum ferritin concen-
the women in each feeding group (lactating and nonlactating) to tration. Similar analyses were performed for the secondary out-
receive either 1 g Ca/d as calcium carbonate (Os-Cal; Marion comes of hemoglobin concentration, MCV, and hematocrit. The
Merrell Dow, Kansas City, MO) or a placebo containing lactose. distribution of serum ferritin concentrations was skewed upward

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Both subjects and study personnel were blinded to calcium treat- so the square roots of the ferritin values were used in all analy-
ment assignment. The supplements were provided as two tablets ses. Potential confounders considered in the analyses included
containing 500 mg Ca each, and subjects were instructed to con- lactation group (lactating or nonlactating), dietary iron and vita-
sume the supplement at two separate meals to facilitate absorption min C intakes during the study, and duration of iron supplement
of the calcium. There was no measure of whether the supplements use before enrollment. Interaction terms with calcium-supple-
were consumed with meals. The calcium supplement and placebo mentation group (supplement or placebo) and baseline iron sta-
were consumed for 6 mo. Compliance with supplementation was tus and lactation group were also tested.
determined by pill counts performed every 3 mo. All women in the The effects of lactation on iron status were evaluated in two
study had low to moderate habitual calcium intakes (≤ 800 mg/d) ways. First, cross-sectional analyses were performed by compar-
as determined by a food-frequency questionnaire (14) as part of ing mean serum ferritin concentrations at baseline (ie, <6 mo
the main trial design. Subjects were also given a standard multivi- postpartum) between lactating and nonlactating women. Analy-
tamin containing 60 mg vitamin C to consume daily throughout sis of covariance was used to adjust for differences in the dura-
the study and were asked to discontinue use of all other vitamin tion of postpartum use of iron-containing supplements between
and mineral supplements before enrollment. groups. Second, we compared the changes in serum ferritin con-
Blood samples were obtained at enrollment (ie, <6 mo post- centrations that occurred in lactating women coincident with
partum) and 12 and 24 wk after calcium supplementation began weaning with the changes observed in nonlactating women over
(ie, 9 and 12 mo postpartum). Hemoglobin, hematocrit, and mean the same time interval by using analysis of covariance. These
corpuscular volume (MCV) were measured immediately in the changes were calculated as the differences between serum fer-
clinical laboratory at Children’s Hospital Medical Center. Serum ritin concentrations at baseline (<6 mo postpartum), when lac-
samples were frozen at 270 °C for ferritin and C-reactive protein tating women were still fully breast-feeding, and serum ferritin
(CRP) determinations so that all samples for a given subject could concentrations at 9 and 12 mo postpartum (all lactating women
be included in the same assay. Serum ferritin was measured by a had completely ceased breast-feeding by 9 mo postpartum).
double-antibody radioimmunoassay (Diagnostic Products Corpo- Duration of postpartum iron supplement use, calcium supple-
ration, Los Angeles). The intraassay and interassay CVs in our ment group, and dietary iron and vitamin C intakes were
laboratory for the low control (35 mg ferritin/L) were 10.5% and included as covariates in the analyses.
17.7% and for the high control (189 mg ferritin/L) were 4.0% and All analyses were performed with and without subjects with
5.3%, respectively. Subjects were classified as having depleted positive CRP results. Because the results were not appreciably
iron stores (ferritin < 12 mg/L), microcytosis (MCV < 80 fL), or altered when subjects with positive CRP results were excluded,
anemia (hemoglobin < 120 g/L) (16). CRP was measured by a only results for the whole sample are presented. Statistical analy-
latex agglutination test (IMMUNEX CRP; Wampole Laboratories, ses were performed with JMP statistical software (version 3;
Cranbury, NJ). This test provided qualitative information: samples SAS Institute Inc, Cary, NC).
were either positive or negative for CRP. Positive and negative
controls were run with each sample. CRP was measured to control
for the potential effects of inflammation and infection on serum RESULTS
ferritin concentrations because ferritin and CRP are both increased There were no significant differences among groups in age,
in these situations (15, 16). parity, dietary iron intake, or vitamin C intake during the study
Subjects kept two 3-d food records during the study, during (Table 1). At enrollment, only 14.5% of lactating women had
the 11th and 23rd study weeks. Nutrient intake was estimated resumed menses whereas 98.8% of nonlactating women had;
with the NUTRITION DATA SYSTEM (University of Min- these proportions did not differ by calcium supplement group.
nesota Coordinating Center, Minneapolis). Information on iron All but one woman in the lactating group had resumed menses by
supplement use before enrollment in the study was recorded. the end of the study (ie, <12 mo postpartum).
Subjects were questioned about brand names, iron content, fre- By design, all women had taken prenatal vitamin and mineral
quency, and duration of use of multivitamins, prenatal vitamins, supplements during pregnancy that contained 60–90 mg Fe. In
and iron supplements. addition to prenatal vitamin and mineral supplements, 25%
The study was approved by the Institutional Review Board at (39/158) of women took supplemental iron during pregnancy for
Children’s Hospital Medical Center and all women provided a mean (± SD) of 6.4 ± 2.6 mo. There was variable use of iron-
1246 KALKWARF AND HARRAST

TABLE 1
Descriptive characteristics of the study subjects1
Lactating women Nonlactating women
Calcium (n = 38) Placebo (n = 38) Calcium (n = 40) Placebo (n = 42)
Age (y) 30 ± 32 31 ± 3 31 ± 3 31 ± 4
Parity 2±1 2±1 2±1 2±1
Height (m) 164.5 ± 6.7 163.9 ± 6.7 165.0 ± 6.9 164.9 ± 6.0
Weight (kg)2 60.7 ± 14.03 61.4 ± 10.83 65.1 ± 11.8 66.4 ± 10.5
Dietary iron intake (mg/d) 13.2 ± 4.7 14.0 ± 4.2 13.3 ± 6.0 12.1 ± 3.7
Dietary vitamin C intake (mg/d) 69 (41, 114) 4 66 (34, 128) 64 (37, 112) 54 (29, 100)
Dietary calcium intake (mg/d) 684 ± 239 776 ± 222 744 ± 214 679 ± 212
Percentage of women who took ≥ 80% of pills (%) 92.1 94.7 87.5 85.7
Menses at enrollment 5/38 5 6/38 5 40/40 41/42
Time to resumption of menses (wk postpartum) 30 ± 7 5 29 ± 9 5 8±2 8±5
Breast-feeding at enrollment (no. of feeds/d) 5.5 ± 1.1 5.3 ± 1.2 — —

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Total duration of lactation (wk) 31.4 ± 5.7 29.7 ± 6.4 — —
Time to complete weaning after enrollment (wk) 7.9 ± 3.7 7.1 ± 3.7 — —
Duration of iron supplement use postpartum,
tertile distribution (%)
0–0.5 mo (n = 49) 133 10.53 45.0 52.4
0.5–4.0 mo (n = 56) 31.63 34.23 35.0 40.5
> 4.0 mo (n = 53) 55.33 52.33 20.0 7.1
1
Women in the calcium and placebo groups received 500 mg Ca as calcium carbonate or placebo twice daily with meals, respectively.
2 –x ± SD.
3, 5
Significantly different from nonlactating women: 3 P < 0.05, 5 P < 0.01 (tested as the main effect of lactation).
4
Geometric mean (± 1 SD). Vitamin C intake does not include the 60 mg contained in the daily multivitamin supplement.

containing supplements postpartum before enrollment into the line, serum ferritin concentrations differed between the lactating
study: 78% reported taking prenatal vitamin and mineral supple- and nonlactating groups (see the next section), but there were no
ments or other multivitamins containing iron postpartum and significant differences between the calcium-supplemented and
15% reported taking iron supplements postpartum. Almost all placebo groups within each lactation group or averaged across
subjects who took supplements reported that they took them lactation groups (P > 0.40). Calcium supplementation did not
daily. Because many women could not remember the brand name significantly affect serum ferritin concentrations. The supple-
or the iron content of the supplement they consumed, subjects ment group 3 time interaction term, which formally tests the
were classified according to the maximum duration of iron or effect of calcium supplementation, was not significant (P = 0.8),
iron-containing supplement use. The tertile distributions of dura- and the three-way interaction term (lactation group 3 supple-
tion of iron-containing supplement use by lactation and calcium ment group 3 time) also was not significant (P = 0.16). At the
supplement groups are given in Table 1. Lactating women were end of the study (<12 mo postpartum), the geometric mean
more likely than nonlactating women to take iron or iron-con- serum ferritin concentrations (21 SD, +1 SD) averaged across
taining supplements postpartum (92% compared with 71%, lactation groups were 28.4 (12.3, 51.0) mg/L in the calcium-sup-
respectively, P < 0.0001) and took them longer. plemented women and 27.5 (9.3, 55.0) mg/L in the placebo-sup-
Overall, 60 of 457 (13%) serum samples tested positive for plemented women (P = 0.7). The results did not change 1) when
CRP, and there were no differences in the proportion testing pos- the outcome variable was expressed as change from baseline (eg,
itive across the four study groups at any sampling time (data not final 2 initial serum ferritin concentration) and dietary iron and
shown). There were insufficient serum samples available to per- vitamin C intakes and iron supplementation use postpartum were
form the CRP test on 17 samples (3.6% of the total). One subject included as covariates in the analyses, or 2) when the sample was
was excluded from all subsequent statistical analyses because restricted to the 142 women whose baseline serum ferritin con-
her initial serum ferritin concentration was 465 mg/L, which was centration was ≥ 12 mg/L. Furthermore, the proportion of sub-
14.5 SDs above the group mean. The mean serum ferritin con- jects with depleted iron stores (serum ferritin < 12 mg/L) at the
centration was higher for samples that tested positive for CRP end of study did not differ between calcium-supplemented
than for those that tested negative (P < 0.01): the geometric (15.6%) and placebo (21.2%) groups (P = 0.4).
means (21 SD, +1 SD) were 40.3 (14.4, 79.2) and 31.9 (13.2, Mean hemoglobin concentrations, MCV, and hematocrit by
59.1) mg/L, respectively. Hemoglobin concentration, MCV, and lactation and calcium-supplementation groups are given in Table
hematocrit did not differ between CRP-positive and CRP-nega- 2. As for serum ferritin, there was no effect of calcium supple-
tive samples (P ≥ 0.3). mentation on these indicators of iron status (P ≥ 0.3).
Effects of calcium supplementation on iron status Effects of lactation on iron status
The mean serum ferritin concentrations of each of the four At baseline, serum ferritin concentrations were significantly
study groups during the study are shown in Figure 1. At base- higher in lactating than in nonlactating women; the geometric
 CALCIUM SUPPLEMENTATION AND IRON STORES 1247

mo postpartum in women who were previously lactating was

17.6 ± 2.3 mg/L compared with 7.1 ± 2.1 mg/L in nonlactating
women (P < 0.01). By the end of the study (12 mo postpartum),
there was no difference in serum ferritin concentrations between
previously lactating women and nonlactating women; the geo-
metric means were 30.5 and 25.5 mg/L, respectively (P = 0.14).
Changes in hemoglobin concentration, MCV, and hematocrit
over the study did not differ between lactating and nonlactating
women whether or not previous postpartum iron supplementa-
tion or iron intake during the study was included in the analyses
(P > 0.2).
We investigated whether the length of postpartum amenorrhea
could account for some of the variability in serum ferritin con-
centration among lactating women and whether it was associated
with the decreased serum ferritin concentrations after weaning.

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There was no difference in baseline serum ferritin concentrations
among lactating women who had resumed menses before enroll-
FIGURE 1. Effects of calcium supplementation and lactation on ment (n = 11) and those who had not (n = 65); the geometric
serum ferritin concentrations. Points represent the geometric mean fer- means were 44.7 and 48.2 mg/L, respectively (P = 0.7). Further-
ritin concentration for each group. Women received 500 mg Ca as calci-
more, the length of postpartum amenorrhea in lactating women
um carbonate or placebo twice daily with meals. Lactating women were
breast-feeding an average of 5.4 times daily at baseline; the arrow
was not associated with the change in serum ferritin concentra-
labeled “weaned” indicates the average time of complete cessation of tion during the 6-mo study (P > 0.3).
breast-feeding. Calcium effect (calcium group 3 time interaction),
P = 0.8; lactation effect (lactation group 3 time interaction), P < 0.001.
Serum ferritin concentrations were significantly greater for lactating DISCUSSION
than for nonlactating women at baseline (P < 0.001) and significantly
Effects of calcium supplementation on iron status
decreased over time (P < 0.01).
The goals of the present study were to determine whether long-
means (21 SD, +1 SD) were 47.7 (22.4, 82.3) and 31.5 (12.6, term calcium supplementation has a deleterious effect on iron sta-
58.9) mg/L, respectively (P < 0.001). There were no significant tus in women in the postpartum period and to describe the effects
differences in baseline hemoglobin concentrations, MCV, or of lactation and weaning on maternal iron status. We found that
hematocrit between lactating and nonlactating women (Table 2; consumption of supplements containing 500 mg Ca twice daily for
P ≥ 0.07). Because the duration of iron supplementation post- 6 mo did not alter serum ferritin concentrations, despite the fact
partum differed between lactating and nonlactating women, it that women were instructed to consume their calcium supplement
was necessary to adjust for this potentially confounding factor in at mealtime, a regimen that should have maximized the potential
the analyses. Categorizing the duration of iron supplement use inhibitory effect of calcium on iron absorption. These findings
into tertiles provided a better statistical fit than did including provide reassurance that consumption of calcium supplements
duration as a continuous variable. The magnitude of the differ- with the goal of optimizing bone health should not have the nega-
ence in serum ferritin concentrations between groups and the sta- tive consequence of compromising iron status.
tistical significance diminished after duration of iron supple- Several studies using radioisotopes to label iron in meals have
mentation use postpartum was controlled for; however, serum shown that calcium inhibits both heme- and nonheme-iron
ferritin concentrations still remained higher in lactating women absorption from a test meal and that the inhibitory effect occurs
than in nonlactating women after this adjustment. The adjusted for a variety of calcium salts (3, 4, 6). Although calcium may
means (21 SEM, +1 SEM) were 44.0 (40.7, 47.5) and 34.5 decrease iron absorption from a test meal, our data indicate that
(31.6, 37.4) mg/L, respectively (P = 0.044). daily calcium supplementation does not significantly reduce
Serum ferritin concentrations decreased significantly in lac- serum ferritin concentrations or result in overt iron deficiency.
tating women after they weaned their infants, and the difference Our sample size was sufficient for detecting a minimum differ-
in serum ferritin concentrations between women who were pre- ence in serum ferritin concentration of <7 mg/L between the cal-
viously lactating and nonlactating women diminished over time. cium-supplemented and placebo groups with 80% power. Our
The mean (± SD) decreases in serum ferritin concentrations at 9 findings are consistent with those from one other study in which
and 12 mo postpartum (1.2 and 4.2 mo after complete weaning, calcium supplements were provided twice daily with meals,
respectively) were 13.9 ± 16.4 and 18.4 ± 17.5 mg/L for lactat- although the calcium dose used in that study was 250 mg Ca
ing women compared with 2.3 ± 17.7 and 6.2 ± 19.1 mg/L for compared with 500 mg Ca in this study (11). In that study, both
nonlactating women. The percentage of lactating women with the iron intake (15.1 mg/d) and vitamin C intake (227 mg/d) of
depleted iron stores (serum ferritin < 12 mg/L) increased from the study subjects were high, which may have overcome any
6.7% at baseline when the women were fully lactating to 19.7% potential inhibitory effect on iron absorption. Our failure to find
at the end of the study, an average of 4.2 mo after weaning an effect of calcium supplements on serum ferritin cannot be
(P = 0.03). The respective percentages for nonlactating women explained by an abundance of dietary iron compensating for
were 11.1% and 17.2% (P = 0.37). After adjustment for postpar- reduced absorption efficiency because serum ferritin concentra-
tum iron supplement use and dietary iron intake during the study, tions decreased among lactating women after weaning when
the mean (± SEM) decrease in serum ferritin concentration by 12 menstrual blood loss resumed.
1248 KALKWARF AND HARRAST

TABLE 2
Effects of calcium supplementation and lactation group on hematologic indicators of iron status1
Lactating women Nonlactating women
Calcium (n = 38) Placebo (n = 38) Calcium (n = 40) Placebo (n = 42)
Hemoglobin (g/L)
Baseline (6 mo) 135 ± 8 133 ± 7 132 ± 7 132 ± 8
9 mo2, 3 134 ± 8 131 ± 6 129 ± 8 131 ± 8
12 mo2 133 ± 7 130 ± 6 129 ± 7 130 ± 8
Mean corpuscular volume (fL)
Baseline (6 mo) 89 ± 4 89 ± 4 88 ± 4 88 ± 4
9 mo2 89 ± 3 89 ± 4 88 ± 4 88 ± 4
12 mo2 90 ± 4 88 ± 4 88 ± 4 88 ± 4
Hematocrit
Baseline (6 mo) 0.39 ± 0.03 0.39 ± 0.02 0.39 ± 0.02 0.39 ± 0.02
9 mo2, 3 0.39 ± 0.02 0.39 ± 0.02 0.38 ± 0.02 0.38 ± 0.02

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12 mo2, 3 0.40 ± 0.03 0.38 ± 0.02 0.38 ± 0.02 0.38 ± 0.02
1 –
x ± SD. Women in the calcium and placebo groups received 500 mg Ca as calcium carbonate or placebo twice daily with meals, respectively.
2
Lactating women had completely weaned their infants and were no longer lactating at these times.
3
Main effect of lactating compared with nonlactating, P < 0.05.

There are several possible reasons we did not find an effect of ered at risk for impaired iron stores, not iron-deficient erythro-
long-term calcium supplementation on serum ferritin concentra- poiesis. We chose to measure serum ferritin concentrations
tions. The moderate amount of calcium in the diet may have been because these are thought to best reflect iron stores and are the
enough to maximally inhibit iron absorption so that no further most sensitive indicator of iron status in well-nourished popula-
inhibition occurred with calcium supplementation. The tions. Furthermore, we measured CRP to rule out potential spu-
inhibitory effect of calcium on iron absorption from test meals rious results due to increases in ferritin secondary to inflamma-
has been shown to be dose dependent up to <165–300 mg, with tion and infection (15, 16).
no further increase in inhibition between 300 and 600 mg Ca (5).
Effects of lactation on iron status
It is also possible that women took their supplements between
meals rather than with their meals as instructed, thereby mini- We found that lactating women had greater serum ferritin con-
mizing the potential for inhibition of iron absorption. centrations, and presumably iron stores, than nonlactating
Alternately, the test meal approach may overestimate the women in the postpartum period and that serum ferritin concen-
inhibitory effect of calcium on iron absorption, and the true trations decreased after weaning. The higher serum ferritin con-
inhibitory effect on iron absorption in the context of a complete centrations at baseline in lactating women may have been due in
diet may be small. Studies using isotopically labeled single test part to the increased use of iron supplements by lactating women
meals have found that calcium reduces iron absorption by <50% before enrollment in the study. However, serum ferritin concen-
(3, 4, 6), whereas the inhibitory effect is <25% when iron trations were still higher in lactating women after prior iron sup-
absorption is measured from the whole diet (17, 18). Further- plement use was statistically controlled for.
more, balance studies in which subjects consume complete Prolonged postpartum amenorrhea in lactating women likely
meals have generally not found an inhibitory effect of calcium contributed to the differences in serum ferritin concentrations
on net iron absorption (19–21). The complex interplay of between lactating and nonlactating women. Only 14.5% of lactat-
enhancing and inhibiting factors in a complete diet makes it dif- ing women had resumed menses by 6 mo postpartum (baseline)
ficult to predict the overall effect of diet on iron absorption (22). whereas 98.8% of nonlactating women had resumed menses by
Last, iron absorption appears to be a highly regulated process, this time. Menstrual blood iron loss is estimated to be 0.5 mg/d
although the exact mechanisms are unknown. Iron absorption is (23) in contrast with iron losses in breast milk of 0.24 mg/d (24).
inversely related to iron stores and the serum ferritin concentra- The drop in serum ferritin concentrations in lactating women after
tion has been shown to be the most important determinant of iron weaning may also have been due to the return of menses, which
absorption from a complete diet (22). It is possible that the ini- occurred in all but one of the participants by the final measurement
tial inhibitory effect of calcium on iron absorption diminishes taken in the study at 12 mo postpartum. We were unable to show
over time in the presence of daily calcium supplementation. Fur- a relation between the length of postpartum amenorrhea and
thermore, it is not known whether low iron absorption at one change in serum ferritin concentration. It is possible that length of
meal enhances absorption at another. postpartum amenorrhea is too crude of a measure to adequately
One limitation of this study is that we measured indicators of quantify the variability in iron loss with menses. Differences in
iron status that best reflect the extremes in iron nutriture (ie, iron volume of menstrual blood loss constitute the largest source of
stores, microcytosis, and anemia) and did not measure indicators variability in iron status in menstruating women (23, 25). The vari-
that reflect iron-deficient erythropoiesis, the intermediate stage ability in menstrual blood loss may be even greater postpartum
of iron deficiency after depletion of iron stores (15). It is possi- because first menstrual cycles in lactating women may be anovu-
ble that we missed an effect of calcium supplementation on iron latory, irregular, and of short duration (26).
status that we could have detected by measuring serum transfer- Whether other hormonal or metabolic changes that accompany
rin receptor concentrations, transferrin saturation, or erythrocyte lactation also contributed to the differences in serum ferritin con-
protoporphyrin. However, the subjects in this study were consid- centration are unknown. Some acute phase proteins (eg, cerulo-
 CALCIUM SUPPLEMENTATION AND IRON STORES 1249

plasmin) are increased in lactation whereas others (eg, CRP and ment of the iron nutritional status of the United States population.
a1-antitrypsin) are not (27). Theoretically, redistribution of iron Am J Clin Nutr 1985;42:1318–30.
among different body pools may also occur to facilitate transfer of 10. Yan L, Prentice A, Dibba B, Jarjou LMA, Stirling DM. The effect of
iron to the mammary glands for milk production. To our knowl- long-term calcium supplementation on indices of iron, zinc, and
magnesium status in lactating Gambian women. Br J Nutr
edge there are no reports that systematically evaluated the effects
1996;76:821–31.
of lactation and weaning on maternal iron status or iron metabo- 11. Sokoll LJ, Dawson-Hughes B. Calcium supplementation and
lism. We presume that the decrease in serum ferritin concentra- plasma ferritin concentrations in premenopausal women. Am J Clin
tions that we observed after weaning was a consequence of wean- Nutr 1992;56:1045–8.
ing because we did not see a comparable decrease in the 12. Kalkwarf HJ, Specker BL. Bone mineral loss during lactation and
nonlactating women at the same time postpartum. However, we recovery after weaning. Obstet Gynecol 1995;86:26–32.
did not follow lactating women who continued to breast-feed after 13. Kalkwarf HJ, Specker BL, Bianchi DC, Ranz J, Ho M. The effect of
9 mo postpartum, so we do not know whether serum ferritin con- calcium supplementation on bone density during lactation and after
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Despite the decrease in serum ferritin concentrations that 14. Cummings SR, Block G, McHenry K, Baron RB. Evaluation of two
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