Biomedical subjects

Bo Lönnerdal

Publications and source records attributed to Bo Lönnerdal.

At least 19 recordsLinked to original sources

PubMed2006

Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency.

Breast milk normally contains adequate zinc to meet infant requirements up to six months of age; however, transient neonatal zinc deficiency has been documented in exclusively breastfed infants of women with low milk zinc concentration. This condition is not corrected by maternal zinc supplementation, supporting the speculation that it results from an inherited genetic condition. We identified a family in which two exclusively breast-fed infants developed zinc deficiency that was associated with low milk zinc concentration in both women. Sequencing of genomic DNA detected a mis-sense mutation (Ade-->Gua) that substitutes a conserved histidine at amino acid 54 with arginine (H54R) in SLC30A2 (ZnT-2) that is present in both affected subjects and several other siblings. Gene knockdown of SLC30A2 in mammary epithelial cells reduced zinc secretion, illustrating the role of ZnT-2 in zinc secretion from this cell type. Expression of the H54R mutant in human embryonic kidney-293 cells resulted in reduced zinc secretion as a consequence of perinuclear, aggresomal accumulation, whereas co-expression of the H54R mutant and wild-type ZnT-2 did not abrogate increased zinc secretion in cells overexpressing wild-type ZnT-2 alone. Together, these data provide evidence that low milk zinc concentration in some women is a consequence of a genetic disorder resulting from a mutation in SLC30A2 and can result in neonatal zinc deficiency if unrecognized. Further studies are needed to evaluate the incidence and penetrance of this mutation in the human population.

Amino Acid Sequence↗

PubMed2006

Mammary gland copper transport is stimulated by prolactin through alterations in Ctr1 and Atp7A localization.

Milk copper (Cu) concentration declines and directly reflects the stage of lactation. Three Cu-specific transporters (Ctr1, Atp7A, Atp7B) have been identified in the mammary gland; however, the integrated role they play in milk Cu secretion is not understood. Whereas the regulation of milk composition by the lactogenic hormone prolactin (PRL) has been documented, the specific contribution of PRL to this process is largely unknown. Using the lactating rat as a model, we determined that the normal decline in milk Cu concentration parallels declining Cu availability to the mammary gland and is associated with decreased Atp7B protein levels. Mammary gland Cu transport was highest during early lactation and was stimulated by suckling and hyperprolactinemia, which was associated with Ctr1 and Atp7A localization at the plasma membrane. Using cultured mammary epithelial cells (HC11), we demonstrated that Ctr1 stains in association with intracellular vesicles that partially colocalize with transferrin receptor (recycling endosome marker). Atp7A was primarily colocalized with mannose 6-phosphate receptor (M6PR; late endosome marker), whereas Atp7B was partially colocalized with protein disulfide isomerase (endoplasmic reticulum marker), TGN38 (trans-Golgi network marker) and M6PR. Prolactin stimulated Cu transport as a result of increased Ctr1 and Atp7A abundance at the plasma membrane. Although the molecular mechanisms responsible for these posttranslational changes are not understood, transient changes in prolactin signaling play a role in the regulation of mammary gland Cu secretion during lactation.

Adenosine Triphosphatases↗

PubMed2006

Do indicators of maternal iron status reflect placental iron status at delivery?

Indicators of maternal iron (Fe) status were studied in relation to placental Fe (Pl-Fe) status. Placental (Pl) and maternal (M) venous blood samples were obtained from primiparous women (n = 38), with normal delivery at Paroissien Hospital, Argentina. Maternal hemoglobin (M Hb), soluble transferrin receptor (M sTfR) (ELISA) and serum ferritin (M S-Ft) were studied in relation to Pl-Fe, ferritin (Pl-Ft) and transferrin receptor (Pl-TfR). Pl-TfR was measured by dot blot assay, Pl-Ft and M S-Ft by immunoassay (IRMA) and Pl-Fe by atomic absorption spectrometry. Fe status indicators were, respectively, (mean +/- SD): M Hb 113 +/- 16 g/L; M S-Ft 36 +/- 42 microg/L; M sTfR 6.3 +/- 3.1 mg/L; Pl-Fe 170 +/- 56 microg/g placenta; Pl-Ft 33 +/- 18 microg/g placenta; Pl-TfR 18 +/- 18 (range 0-58) microg/g placenta. Pl-Fe, Pl-Ft and Pl-TfR did not correlate to M Hb, M S-Ft and M sTfR. Women with Pl- Fe, Pl-Ft and Pl-TfR above or below the corresponding median values did not show any statistical significant difference in M Hb, M sTfR or M S-Ft values. Pl-Ft concentration was lower in women with Hb < 110 g/L than in women with normal values: 26 +/- 13 vs. 38 +/- 20 microg/g, respectively (p = 0.021). When Pl-TfR, Pl-Ft and Pl-Fe were compared in women with M S-Ft above or below the cut-off point of 10 or 20 microg/L, no significant difference was found for Pl-TfR neither for Pl-Ft nor Pl-Fe. These results suggest that maternal indicators of Fe status, particularly M sTfR and M S-Ft, do not reflect Fe status of the placenta at delivery.

Adolescent↗

PubMed2006

Iron absorption from soybean ferritin in nonanemic women.

BACKGROUND: Dietary ferritin, a protein cage around an iron mineral, is an underestimated source of bioavailable iron. Plant ferritin, the most common dietary ferritin, has not been studied. Iron from animal ferritin is absorbed as well as is iron from FeSO4 in women. OBJECTIVE: The objective was to examine iron absorption from purified soybean ferritin. DESIGN: Healthy, nonanemic women (n = 16) were fed a standardized meal (bagel, cream cheese, and apple juice) containing 1 microCi 59Fe/meal as FeSO4 or (extrinsically labeled) as iron-free soybean ferritin reconstituted with the high phosphate characteristic of plant ferritin (iron:phosphorus = 4:1). Iron-free, apo-soybean ferritin was prepared (with the use of thioglycolic acid and extensive dialysis) from purified ferritin. In a randomized crossover design, the other labeled meal, which contained FeSO4 or ferritin, was given after 4 wk. The subjects received 140 microg Fe as ferritin (2.5 mg) or as FeSO4. After 28 d, whole-body 59Fe and 59Fe in red blood cells were measured before and after dosing. RESULTS: There was no significant difference in whole-body iron absorption from soybean ferritin (29.9 +/- 19.8%) and that from FeSO4 (34.3 +/- 23.6%) or in iron absorption calculated from red blood cell incorporation (33.0 +/- 20.1% for soybean ferritin and 35.3 +/- 23.4% for FeSO4), which confirmed previous results with animal ferritin that was mineralized and labeled similarly. An inverse relation was observed between serum ferritin and iron absorption from both ferritin and FeSO4, which suggested that sensors regulating iron absorption respond similarly to iron provided as ferrous salts or as ferritin mineral. CONCLUSION: Iron from soybean ferritin is well absorbed and may provide a model for novel, utilizable, plant-based forms of iron for populations with a low iron status.

Adult↗

PubMed2006

Absorption of iron from recombinant human lactoferrin in young US women.

BACKGROUND: Lactoferrin is a major protein component of human milk, and it binds iron with high affinity. Because the human small intestine has receptors for lactoferrin, a role for it in iron absorption has been suggested. OBJECTIVE: The objective was to study the absorption of iron from extrinsically labeled purified recombinant human lactoferrin produced in rice and to compare it with the absorption of iron from ferrous sulfate. DESIGN: On 2 occasions 4 wk apart, healthy young women (n = 20) were fed a standardized meal supplemented in randomized order with 59Fe as lactoferrin or as ferrous sulfate. Ten subjects received lactoferrin that had been heat-treated, and 10 subjects received untreated lactoferrin. Iron absorption was measured in a whole-body counter after 14 and 28 d and also was measured by red blood cell incorporation after 28 d. RESULTS: The difference in whole-body iron absorption between heat-treated (24.6 +/- 20.8%; n = 10) and untreated (16.2 +/- 4.4%; n = 10) lactoferrin was not significant. The difference in whole-body iron absorption between the groups given lactoferrin (20.4 +/- 15.3%; n = 20) or ferrous sulfate (18.8 +/- 13.2%; n = 20) also was not significant. Serum ferritin and iron absorption were inversely correlated in subjects when they received either lactoferrin or ferrous sulfate, which suggested that iron is absorbed from the 2 sources by a similar mechanism. CONCLUSIONS: Iron is equally well absorbed from lactoferrin (whether heat-treated or untreated) and ferrous sulfate. Thus, iron provided by dietary lactoferrin is likely to be well utilized in human adults.

Adult↗

PubMed2006

Zinc supplementation does not affect growth, morbidity, or motor development of US term breastfed infants at 4-10 mo of age.

BACKGROUND: It has been documented that growth patterns differ between breastfed and formula-fed infants. Some investigators have suggested that these differences may be related to differences in zinc nutriture. OBJECTIVE: The objective of this study was to examine the effect of zinc supplementation on growth, morbidity, and motor development in healthy, term, breastfed infants. DESIGN: We conducted a randomized double-blind intervention comparing zinc supplementation (5 mg/d as zinc sulfate) with placebo in breastfed infants aged 4-10 mo. Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo. Morbidity data were collected weekly. RESULTS: Eighty-five infants were enrolled, and 70 completed the study. The baseline characteristics, attained weight or length at 10 mo, growth velocity, gross motor development, and morbidity did not differ significantly between groups, even after control for potentially confounding variables. CONCLUSIONS: The dietary zinc intake of these breastfed infants appeared to be adequate, given that zinc supplementation did not affect growth, development, or risk of infection (although sample size for detection of differences in development or infection was limited). Previously described differences in growth between breastfed and formula-fed infants in such populations do not appear to be due to differences in zinc nutriture.

Analysis of Variance↗

PubMed2006

Zinc supplementation reduces iron absorption through age-dependent changes in small intestine iron transporter expression in suckling rat pups.

Zinc (Zn) supplementation negatively affects iron (Fe) absorption; however, the molecular mechanisms are not understood. We determined effects of Zn supplementation during mid- and late infancy on intestinal Fe transport mechanisms using a suckling rat model. Suckled rat pups were supplemented with 0 (control), 300 (low), or 750 (high) microg Zn/d until weaning at postnatal day (PN) 20. At mid-(PN10) and late (PN20) infancy, tissue Fe distribution, Fe absorption, intestine DMT1, ferroportin-1 (FPN) and hephaestin expression, and localization and liver hepcidin expression were measured. During early infancy, DMT1 and FPN were localized intracellularly. Negative effects of Zn supplementation on Fe absorption were associated with increased small intestine Fe retention, decreased hephaestin, and increased FPN expression. During late infancy, both DMT1 and FPN were appropriately localized to the apical and basolateral membrane, respectively, and negative effects of Zn supplementation on Fe absorption were absent. Although FPN protein level was lower in Zn-supplemented pups, hephaestin protein level was increased, which may have facilitated enhanced Fe efflux. These results indicate that Zn supplementation reduced Fe absorption during early infancy as a consequence of increased intestinal Fe retention due to reduced hephaestin levels. These effects were age-dependent, further demonstrating that Fe transport regulation is not fully developed until weaning, which may have important implications regarding the safety and efficacy of Zn supplementation programs for infants.

Animals↗

PubMed2006

Iron deficiency, but not anemia, upregulates iron absorption in breast-fed peruvian infants.

Iron absorption in adults is regulated by homeostatic mechanisms that decrease absorption when iron status is high. There are few data, however, regarding the existence of a similar homeostatic regulation in infants. We studied 2 groups of human milk-fed infants using (57)Fe (given as ferrous sulfate without any milk) and (58)Fe (given at the time of a breast-milk feeding) stable isotopes to determine whether healthy infants at risk for iron deficiency would regulate their iron absorption based on their iron status. We studied 20 Peruvian infants at 5-6 mo of age and 18 infants at 9-10 mo of age. We found no effect of infant hemoglobin concentration on iron absorption with 5-6 mo-old infants absorbing 19.2 +/- 2.1% and 9- to 10-mo-old infants absorbing 25.8 +/- 2.6% of the (57)Fe dose. For (58)Fe, 5- to 6-mo-old infants absorbed 42.6 +/- 5.0% and 9 to 10-mo-old infants absorbed 51.9 +/- 10.3%. Following log transformation, iron absorption from (57)Fe (r = -0.61, P = < 0.001) and (58)Fe (r = -0.61, P = < 0.001) were inversely correlated to serum ferritin (S-Ft). For both the (57)Fe and (58)Fe doses, infants with S-Ft <12 mg/L (n = 11) had significantly higher iron absorption than those with S-Ft >12 mg/L. We concluded that iron absorption in infants is related to iron status as assessed by serum ferritin but not hemoglobin concentration. Infants with low iron status upregulate iron absorption from breast milk at both 5-6 and 9-10 mo of age.

Absorption↗

PubMed2006

Effects of bovine alpha-lactalbumin and casein glycomacropeptide-enriched infant formulae on faecal microbiota in healthy term infants.

OBJECTIVE: Certain milk factors may promote the growth of a host-friendly gastrointestinal microbiota, for example, one that is predominated by bifidobacteria, a perceived health-promoting genus. This may explain why breast-fed infants experience fewer intestinal infections than their formula-fed counterparts who are believed to have a more diverse microbiota, which is similar to that of adults. The effects of formulas supplemented with 2 such ingredients from bovine milk, alpha-lactalbumin (alpha-lac) and casein glycomacropeptide (GMP), on gut flora were investigated in this study. PATIENTS AND METHODS: Six-week-old (4-8 wk), healthy term infants were randomised to a standard infant formula or 1 of 2 test formulae enriched in alpha-lac with higher or lower GMP until 6 months. Faecal bacteriology was determined by the culture-independent procedure fluorescence in situ hybridisation. RESULTS: There was a large fluctuation of bacterial counts within groups with no statistically significant differences between groups. Although all groups showed a predominance of bifidobacteria, breast-fed infants had a small temporary increase in counts. Other bacterial levels varied in formula-fed groups, which overall showed an adult-like faecal microflora. CONCLUSIONS: It can be speculated that a prebiotic effect for alpha-lac and GMP is achieved only with low starting populations of beneficial microbiota (eg, infants not initially breast-fed.

Animals↗

PubMed2006

Ontogenic changes in lactoferrin receptor and DMT1 in mouse small intestine: implications for iron absorption during early life.

It has been proposed that lactoferrin receptor (LfR) may be involved in intestinal iron transport during early life. However, it is known that iron homeostasis is regulated by divalent metal transporter 1 (DMT1; Nramp2/DCT1) in the adult small intestine. To address the hypothesis that LfR may play a role as an alternative iron transport pathway during early life, we used immunohistochemistry (IHC) to examine the localization of mouse LfR (mLfR) and DMT1. In addition to studying the localization and abundance of LfR and DMT1 on the apical membrane, intestinal brush-border membrane vesicles (BBMV) were isolated during the first 3 postnatal weeks (postnatal day (PD) 0, 5, 10, and 20). We found that mLfR is expressed in fetal mice as early as gestational days (GD) 13.5, 15.5, and 18.5. A 34 kD band for mLfR was detected at PD 0 through PD 20 in total intestine homogenate. However, mLfR protein did not appear in the BBMV preparations until PD 5 and was highly expressed at PD 10. By IHC, DMT1 protein was minimally observed at PD 0 and PD 5, but by PD 10 DMT1 was predominantly localized in the apical membrane of the maturing intestine. BBMV fractionation revealed 50-120 kD protein bands for DMT1. In these BBMV preparations, the apical-membrane-associated 120 kD band for DMT1 increased in abundance with age. However, in the corresponding total homogenates, only the deglycosylated form of DMT1 (50 kD) was identified. These results indicate that DMT1 is mislocalized during late gestation, minimally expressed during early life, and predominantly expressed in its deglycosylated form until PD 20. The immunolocalization and abundant protein expression of mLfR suggest that accrual of iron from Lf may be the principal iron uptake pathway at this age. In conclusion, our findings support the notion that until the development-dependent expression of DMT1 in the intestine is induced, mLfR may serve as an alternative iron uptake pathway.

Animals↗

PubMed2006

Recombinant human milk proteins.

Human milk provides proteins that benefit newborn infants. They not only provide amino acids, but also facilitate the absorption of nutrients, stimulate growth and development of the intestine, modulate immune function, and aid in the digestion of other nutrients. Breastfed infants have a lower prevalence of infections than formula-fed infants. Since many women in industrialized countries choose not to breastfeed, and an increasing proportion of women in developing countries are advised not to breastfeed because of the risk of HIV transmission, incorporation of recombinant human milk proteins into infant foods is likely to be beneficial. We are expressing human milk proteins known to have anti-infective activity in rice. Since rice is a normal constituent of the diet of infants and children, limited purification of the proteins is required. Lactoferrin has antimicrobial and iron-binding activities. Lysozyme is an enzyme that is bactericidal and also acts synergistically with lactoferrin. These recombinant proteins have biological activities identical to their native counterparts. They are equally resistant to heat processing, which is necessary for food applications, and to acid and proteolytic enzymes which are needed to maintain their biological activity in the gastrointestinal tract of infants. These recombinant human milk proteins may be incorporated into infant formulas, baby foods and complementary foods, and used with the goal to reduce infectious diseases.

Humans↗

PubMed2005

Effect of suboptimal nutrition during lactation on milk protein gene expression in the rat.

Human milk provides infants with proteins that aid in the prevention of infections and facilitate the digestion and absorption of other nutrients. Maternal diet is not believed to affect the protein concentration of breast milk. However, the maternal factors that regulate the expression of genes for specific milk proteins are not well characterized. We hypothesized that nutrition could be one of the factors. We fed Sprague-Dawley rats five diets representing common nutrient deficiencies and energy deficiency during pregnancy and lactation: low-zinc (Zn; 7 microg/g), low-iron (Fe; 6 microg/g), low-protein (12.5% albumin), pair-fed control diet (lactation only, 20% less kcal) and control diet (Zn, 25 microg/g; Fe, 100 mug/g; protein, 21%) ad libitum. At day 10 of lactation, the mammary gland was removed for RNA extraction. Northern blots of mRNA from the different groups were performed by hybridization with beta-casein and whey acidic protein (WAP) cDNA probes. The expression of beta-casein mRNA in rat mammary gland was significantly (P<.005) increased in the pair-fed group when compared to the control group. The expression of WAP mRNA was also significantly (P<.005) increased in the pair-fed group as well as in the low-Fe group when compared to the control group. The concentration of beta-casein in milk was significantly higher for the low-zinc and the pair-fed groups only. The concentration of WAP in milk was not different among groups. These results suggest that compromised maternal nutrition can affect the expression of two individual milk proteins and may have functional implications with regard to bioactive proteins in milk.

Animals↗

PubMed2005

Viral, nutritional, and bacterial safety of flash-heated and pretoria-pasteurized breast milk to prevent mother-to-child transmission of HIV in resource-poor countries: a pilot study.

BACKGROUND: Heat-treated breast milk of HIV-positive mothers has potential to reduce vertical transmission. This study compared the impact of flash-heating (FH) and Pretoria pasteurization (PP) on HIV, nutrients, and antimicrobial properties in human milk. METHODS: Milk samples were spiked with 1 x 10 (8) copies/mL of clade C HIV-1 and treated with FH and PP. We measured HIV reverse transcriptase (RT) activity before and after heating (n = 5). Heat impact on vitamins A, B6, B12, and C; folate, riboflavin, thiamin, and antimicrobial proteins (lactoferrin and lysozyme) was assessed. Storage safety was evaluated by spiking with Escherichia coli or Staphylococcus aureus. RESULTS: Both methods inactivated > or = 3 logs of HIV-1. FH resulted in undetectable RT activity. Neither method caused significant decrease in any vitamin, although reductions in vitamins C and E were noted. Heat decreased immunoreactive lactoferrin (P < 0.05) but not the proportions of lactoferrin and lysozyme surviving digestion. FH seems to retain more antibacterial activity. Both treatments eliminated spiked bacteria. CONCLUSIONS: FH may be superior to PP in eliminating all viral activity; both methods retained nutrients and destroyed bacterial contamination. Heat-treated breast milk merits further study as a safe and practical infant feeding option for HIV-positive mothers in developing countries.

Developing Countries↗

PubMed2005

Zip3 plays a major role in zinc uptake into mammary epithelial cells and is regulated by prolactin.

During lactation, a substantial amount of Zn(2+) is transferred by the mammary gland from the maternal circulation into milk; thus secretory mammary epithelial cells must tightly regulate Zn(2+) transport to ensure optimal Zn(2+) transfer to the suckling neonate. To date, six Zn(2+) import proteins (Zip1-6) have been identified; however, Zip3 expression is restricted to tissues with unique requirements for Zn(2+), such as the mammary gland, which suggests that it may play a specialized role in this tissue. In the present study, we have used a unique mammary epithelial cell model (HC11) to characterize the role of Zip3 in mammary epithelial cell Zn(2+) transport. Confocal microscopy demonstrated that Zip3 is localized to the cell surface in mammary epithelial cells and transiently relocalized to an intracellular compartment in cells with a secretory phenotype. Total (65)Zn transport was higher in secreting cells, while gene silencing of Zip3 decreased (65)Zn uptake into mammary epithelial cells, particularly in those with a secretory phenotype. Finally, reduced expression of Zip3 ultimately resulted in cell death, indicating that mammary epithelial cells have a unique requirement for Zip3-mediated Zn(2+) import, which may reflect the unique requirement for Zn(2+) of this highly specialized cell type and thus provides a physiological explanation for the restricted tissue distribution of this Zn(2+) importer.

Animals↗

PubMed2005

Detection of a single nucleotide polymorphism in the human alpha-lactalbumin gene: implications for human milk proteins.

Variability in the protein composition of breast milk has been observed in many women and is believed to be due to natural variation of the human population. Single nucleotide polymorphisms (SNPs) are present throughout the entire human genome, but the impact of this variation on human milk composition and biological activity and infant nutrition and health is unclear. The goals of this study were to characterize a variant of human alpha-lactalbumin observed in milk from a Filipino population by determining the location of the polymorphism in the amino acid and genomic sequences of alpha-lactalbumin. Milk and blood samples were collected from 20 Filipino women, and milk samples were collected from an additional 450 women from nine different countries. alpha-Lactalbumin concentration was measured by high-performance liquid chromatography (HPLC), and milk samples containing the variant form of the protein were identified with both HPLC and mass spectrometry (MS). The molecular weight of the variant form was measured by MS, and the location of the polymorphism was narrowed down by protein reduction, alkylation and trypsin digestion. Genomic DNA was isolated from whole blood, and the polymorphism location and subject genotype were determined by amplifying the entire coding sequence of human alpha-lactalbumin by PCR, followed by DNA sequencing. A variant form of alpha-lactalbumin was observed in HPLC chromatograms, and the difference in molecular weight was determined by MS (wild type=14,070 Da, variant=14,056 Da). Protein reduction and digestion narrowed the polymorphism between the 33rd and 77th amino acid of the protein. The genetic polymorphism was identified as adenine to guanine, which translates to a substitution from isoleucine to valine at amino acid 46. The frequency of variation was higher in milk from China, Japan and Philippines, which suggests that this polymorphism is most prevalent in Asia. There are SNPs in the genome for human milk proteins and their implications for protein bioactivity and infant nutrition need to be considered.

Amino Acid Sequence↗

PubMed2005

Trace element nutrition of infants--molecular approaches.

Newborn infants are exposed to widely varying intakes of trace elements, but little is known about their ability to homeostatically adjust to these intakes. Recent discoveries of several metal ion transporters in the small intestine are likely to enhance our understanding of molecular mechanisms regulating trace element absorption. Iron absorption is regulated by divalent metal ion transporter 1 (DMT1) and ferroportin 1 (FPN1). Studies on human infants have shown that young infants cannot regulate iron absorption, whereas older infants can. Our studies on infant rat pups show that there is no regulation of DMT1 and FPN1 at young age, but that this develops at older age. These findings may explain adverse effects of iron supplementation on growth in young human infants. Zinc absorption in the small intestine is regulated by the transporters ZnT1, ZnT2, ZnT4 and Zip-4 and zinc status affects the expression of these transporters in an attempt to achieve zinc homeostasis. Copper absorption is regulated by the transporters Ctrl, Atp7A and Atp7B, and exposure to copper at early age affects the expression and cellular localization of these proteins, affecting copper uptake and transport. To date, most studies on homeostatic regulation of trace mineral absorption have been done in cell systems and animal models; further studies on human infants are needed. The consequences of trace element interactions during infancy also need to be investigated in more detail.

Animals↗

PubMed2005

Iron supplements reduce erythrocyte copper-zinc superoxide dismutase activity in term, breastfed infants.

AIM: To investigate whether iron supplements compromise copper status in infants. METHODS: 214 healthy, term, breastfed Swedish and Honduran infants were randomized to (1) iron supplements (1 mg/kg/d) from 4-9 mo of age, (2) iron supplements from 6-9 mo, or (3) placebo. Blood samples were obtained at 4, 6, and 9 mo and analyzed for plasma copper (p-Cu) and, at 9 mo, for copper/zinc-dependent superoxide dismutase (CuZn-SOD) activity. RESULTS: P-Cu increased with infant age. At 9 mo, Honduran infants had significantly higher p-Cu (1.40+/-0.29 vs 1.09+/-0.22 mg/l, p<0.001) and CuZn-SOD activity (1.09+/-0.29 vs 0.93+/-0.21 U/mg Hb, p<0.001) than Swedish infants. Infants receiving iron supplements from 4-9 mo had significantly lower CuZn-SOD at 9 mo of age (0.95+/-0.27 vs 1.08+/-0.24 U/mg Hb, p=0.023) than those receiving placebo. CONCLUSION: There is a physiologic increase in p-Cu during the first 9 mo of life. Differences in copper status between Swedish and Honduran infants may be due to genetic or nutritional differences. Iron supplementation decreases CuZn-SOD activity, probably due to a negative effect on copper status. Possible clinical implications remain to be elucidated.

Adult↗

PubMed2005

Iron transporters in rat mammary gland: effects of different stages of lactation and maternal iron status.

BACKGROUND: Mechanisms regulating iron transfer from maternal circulation into milk are yet unknown. Whether intestinal iron transporters, divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), are present in the mammary gland and are involved in iron transfer into milk are unknown. OBJECTIVE: The objective was to examine DMT1 and FPN1 in rat mammary gland at different stages of lactation and to evaluate the effects of maternal iron status. DESIGN: Rats were fed either 35 mg Fe (control rats) or 8 mg Fe (low-iron rats) per kg diet for 3 wk and were fed the same diet throughout pregnancy and lactation. Mammary gland DMT1, FPN1, transferrin receptor, and ferritin were examined in control rats on days 1, 5, 10, and 20 of lactation and in low-iron rats on days 10 and 20 of lactation. Tissue and milk iron were measured. RESULTS: Milk iron, DMT1, and FPN1 decreased throughout lactation. Iron status was compromised in low-iron rats, whereas milk iron was maintained. On day 10 of lactation, mammary gland iron and ferritin were lower in the low-iron rats. DMT1, FPN1, and transferrin receptor values were unchanged; however, a smaller-size DMT1 protein was observed in the low-iron rats. On day 20, transferrin receptor increased in the low-iron rats, whereas mammary gland iron, ferritin, DMT1, and FPN1 were unchanged. CONCLUSIONS: The results show that DMT1 and FPN1 concentrations are higher during early lactation and are possibly involved in iron transfer into milk. Mammary gland regulation of DMT and FPN1 during low iron status appears to be different from that in the intestine.

Animals↗