Biomedical subjects

Bo Lönnerdal

Publications and source records attributed to Bo Lönnerdal.

At least 73 records · Page 4Linked to original sources

PubMed2003

Marginal maternal Zn intake in rats alters mammary gland Cu transporter levels and milk Cu concentration and affects neonatal Cu metabolism.

Marginal zinc intake is common and leaves women particularly vulnerable to Zn deficiency due to increased demand for Zn as a consequence of reproduction. Zn deficiency during pregnancy and lactation has been associated with secondary affects on copper metabolism in the offspring; however, the underlying mechanisms are unknown. The effects of marginal maternal Zn intake on maternal and neonatal Cu metabolism were determined in rats. Plasma, milk and tissue Cu and Zn concentrations and plasma and milk ceruloplasmin (Cp) activity were measured in dams fed a control (CON, 25 mg Zn/kg diet) or a marginal Zn diet (ZD, 10 mg Zn/kg diet) and their suckling pups. There was no effect on maternal tissue Cu or Zn or milk Zn concentration; however, plasma Cp activity was higher in dams fed ZD, suggesting that Cp activity may be a useful marker for identifying marginal Zn status. Rats fed ZD had high mammary gland Ctr1, Atp7A and Atp7B levels, milk Cp activity and Cu concentration. Immunostaining and differential centrifugation indicated that ZD also altered Ctr1 and Atp7A localization in the mammary gland. Pups from dams fed ZD had higher small intestine Cu and lower plasma Cu than CON pups. These results suggest that marginal maternal Zn intake during pregnancy and lactation increase mammary gland Cu transporter levels and alter their localization, resulting in high milk Cu levels, possibly in response to transiently elevated plasma Cu levels. The combination of high milk Cu concentration and immature neonatal Cu transport exposes the suckling neonate to excess Cu; however, whether this occurs in humans is not yet known.

Amino Acid Sequence↗

PubMed2003

Expression, characterization, and biologic activity of recombinant human lactoferrin in rice.

BACKGROUND: Lactoferrin has been suggested to have many biologic activities, such as facilitating iron absorption and having antimicrobial and antiinflammatory effects. In humans, several of these activities are likely to only be facilitated by human lactoferrin because they depend on the binding of human lactoferrin to specific receptors. Rice may be a useful vehicle to introduce recombinant human lactoferrin to infant foods because it has low allergenicity and is likely to be safer than using microorganisms or transgenic animals. METHODS: Recombinant human lactoferrin was expressed in the rice cell culture system, and its biologic activity was assessed by iron-binding and -releasing properties, antimicrobial activity, and binding and uptake to Caco-2 cells. The authors also compared the stability of recombinant and native human lactoferrins against heat, low pH, and in vitro digestion. RESULTS: Biologic activity of rice-expressed recombinant human lactoferrin was similar to that of native human lactoferrin. Heat-treated proteins retained their functional activities except with severe treatment at 100 degrees C for 8 seconds, which disturbed the iron-binding capacity of recombinant human lactoferrin. Both types of proteins retained their functional activities between pH 2 and 7.4. After in vitro digestion, 50% of both proteins were detectable by enzyme linked immunosorbent assay. The remaining native and recombinant lactoferrins retained antimicrobial and Caco-2 binding and uptake activities. CONCLUSIONS: The results indicate recombinant human lactoferrin has stability similar to native human lactoferrin when exposed to thermal treatment, pH treatment, and in vitro digestion, suggesting it may be active when added to infant formula.

Amino Acid Sequence↗

PubMed2003

rRNA probes used to quantify the effects of glycomacropeptide and alpha-lactalbumin supplementation on the predominant groups of intestinal bacteria of infant rhesus monkeys challenged with enteropathogenic Escherichia coli.

OBJECTIVES: Certain milk factors may help to promote the growth of a host-friendly colonic microflora (e.g. bifidobacteria, lactobacilli) and explain why breast-fed infants experience fewer and milder intestinal infections than those who are formula-fed. The effects of supplementation of formula with two such milk factors was investigated in this study. MATERIALS AND METHODS: Infant rhesus macaques were breast-fed, fed control formula, or formula supplemented with glycomacropeptide (GMP) or alpha-lactalbumin (alpha-LA) from birth to 5 months of age. Blood was drawn monthly and rectal swabs were collected weekly. At 4.5 months of age, 10(8) colony-forming units of enteropathogenic E.coli O127, strain 2349/68 (EPEC) was given orally and the response to infection assessed. The bacteriology of rectal swabs pre- and post-infection was determined by culture independent fluorescence in situ hybridization. RESULTS: Post-challenge, breast-fed infants and infants fed alpha-LA-supplemented formula had no diarrhea, whilst those infants fed GMP-supplemented formula had intermittent diarrhea. In infants fed control formula the diarrhea was acute. CONCLUSIONS: Supplementation of infant formula with appropriate milk proteins may be useful for improving the infant's ability to resist acute infection caused by E.coli.

Animals↗

PubMed2003

Detecting Candida albicans in human milk.

Procedures for diagnosis of mammary candidosis, including laboratory confirmation, are not well defined. Lactoferrin present in human milk can inhibit growth of Candida albicans, thereby limiting the ability to detect yeast infections. The inhibitory effect of various lactoferrin concentrations on the growth of C. albicans in whole human milk was studied. The addition of iron to the milk led to a two- to threefold increase in cell counts when milk contained 3.0 mg of lactoferrin/ml and markedly reduced the likelihood of false-negative culture results. This method may provide the necessary objective support needed for diagnosis of mammary candidosis.

Candida albicans↗

PubMed2003

Nutritional and physiologic significance of alpha-lactalbumin in infants.

alpha-Lactalbumin is the major protein in breast milk (20-25% of total protein) and has been described to have several physiologic functions in the neonatal period. In the mammary gland, it participates in lactose synthesis, thereby creating an osmotic "drag" to facilitate milk production and secretion. alpha-Lactalbumin binds divalent cations (Ca, Zn) and may facilitate the absorption of essential minerals, and it provides a well-balanced supply of essential amino acids to the growing infant. During its digestion, peptides appear to be transiently formed that have antibacterial and immunostimulatory properties, thereby possibly aiding in the protection against infection. A novel folding variant ("molten globule state") of multimeric alpha-lactalbumin has recently been discovered that has anti-infective activity and enhances apoptosis, thus possibly affecting mucosal cell turnover and proliferation. Cow milk also contains alpha-lactalbumin, albeit less than human milk (2-5% of total protein in bovine milk), and protein fractions enriched with alpha-lactalbumin may now be added to infant formula to provide some of the benefits of human alpha-lactalbumin.

Amino Acids, Essential↗

PubMed2002

Effects of neonatal dietary manganese exposure on brain dopamine levels and neurocognitive functions.

Neonatal exposure to high levels of manganese (Mn) has been indirectly implicated as a causal agent in attention deficit hyperactivity disorder (ADHD), since Mn toxicity and ADHD both involve dysfunction in brain dopamine (DA) systems. This study was undertaken to examine this putative relationship in an animal model by determining if levels of neonatal dietary Mn exposure were related to brain DA levels and/or behavioral tests of executive function (EF) when the animals reached maturity. We used 32 newborn male Sprague-Dawley rats and randomly assigned them to one of the four dietary Mn supplementation conditions: 0, 50, 250 and 500 microg per day, administered daily in water from postnatal days 1-21. During days 50-64, the animals were given a burrowing detour test and a passive avoidance test. At day 65, the animals were killed and brains were assayed for DA. There was a statistically significant relationship (P = 0.003) between dietary Mn exposure and striatal DA. On the burrowing detour and passive avoidance, greater deficits were observed for animals subjected to higher Mn exposure, but these differences did not reach statistical significance. However, tests for heterogeneity of variance between groups were statistically significant for all measures, with positive relationship between Mn exposure and degree of within-group behavioral variability. Kendall's nonparametric test of the relationship between the three behavioral measures and striatal DA levels was also statistically significant (P = 0.02). These results lend support to the hypothesis that neonatal Mn exposure is related to brain DA levels and neurocognitive deficit in the rodent.

Animals↗

PubMed2002

Effect of high dietary manganese intake of neonatal rats on tissue mineral accumulation, striatal dopamine levels, and neurodevelopmental status.

Mn is an essential element, but may become neurotoxic at high levels. Recent reports of high Mn levels in hair of children with neurodevelopmental deficits suggest that these deficits could be due to Mn-induced neurotoxic effects on brain dopamine (DA) systems, although the mechanism is not well understood. Infant formulas contain considerably higher concentrations of Mn than human milk. Thus, formula-fed infants are exposed to high levels of Mn at a time when Mn homeostasis is incompletely developed. We studied the effects of dietary Mn supplementation of rat pups on tissue Mn accumulation, brain dopamine levels, infant neurodevelopmental status, and behavior at maturity. Newborn rats were supplemented daily with 0, 50, 250, or 500 microg Mn given orally from day 1 to day 20. Mineral analysis of small intestine and brain at day 14 showed a significant increase of tissue Mn in supplemented rats. Neurodevelopmental tests conducted at various ages showed significant delays as a function of Mn supplementation. At day 32, there was a significant positive relationship between passive avoidance errors and Mn supplementation levels. Brains of animals killed on day 40 showed a significant inverse relationship between Mn supplementation level and striatal dopamine concentration. These observations suggest that dietary exposure to high levels of Mn during infancy can be neurotoxic to rat pups and result in developmental deficits.

Animals↗

PubMed2002

Expression of human milk proteins in plants.

Human milk proteins are believed to have a multitude of biological activities benefiting the newborn infant. Such functions include antibacterial and antiviral activities, enhancement of the immune system and increased nutrient absorption. To date, only breast-fed infants have been exposed to these proteins. However, by using genetic engineering it is now possible to express these proteins in plants, such as rice, at very high levels. Recombinant human milk proteins can subsequently be added to infant formula and baby foods. Prior to such addition, safety tests and efficacy trials need to be conducted. The safety tests will initially be done in rats and then in humans. The efficacy trials should also evaluate stability against heat treatment (processing), pH (stomach conditions) and proteolytic enzymes (digestion). To date, we have expressed recombinant human lactoferrin, lysozyme and alpha1-antitrypsin in rice at very high expression levels. These recombinant proteins showed a stability and activities similar to those of the native milk proteins, suggesting that they may be able to exert biological activities in infants when added to formula or baby foods.

Humans↗

PubMed2002

Iron absorption in breast-fed infants: effects of age, iron status, iron supplements, and complementary foods.

BACKGROUND: Iron supplements are often recommended for older breast-fed infants, but little is known about factors affecting iron absorption from human milk or supplements. OBJECTIVE: We investigated the effects of age, iron status, and iron intake on iron absorption in healthy, term, breast-fed infants. DESIGN: Twenty-five infants were randomly assigned to receive either 1) iron supplements (1 mg x kg(-1) x d(-1)) from 4 to 9 mo of age, 2) placebo from 4 to 6 mo and iron supplements from 6 to 9 mo, or 3) placebo from 4 to 9 mo. Infants were exclusively breast-fed to 6 mo and partially breast-fed to 9 mo of age. Iron absorption was assessed by giving (58)Fe with mother's milk at 6 and 9 mo. Blood samples were obtained at 4, 6, and 9 mo, and complementary food intake was recorded at 9 mo. RESULTS: At 6 mo, mean (+/-SD) fractional iron absorption from human milk was relatively low (16.4 +/- 11.4%), with no significant difference between iron-supplemented and unsupplemented infants. At 9 mo, iron absorption from human milk remained low in iron-supplemented infants (16.9 +/- 9.3%) but was higher (P = 0.01) in unsupplemented infants (36.7 +/- 18.9%). Unexpectedly, iron absorption at 9 mo was not correlated with iron status but was significantly correlated with intake of dietary iron, including supplemental iron. CONCLUSIONS: Changes in the regulation of iron absorption between 6 and 9 mo enhance the infant's ability to adapt to a low-iron diet and provide a mechanism by which some, but not all, infants avoid iron deficiency despite low iron intakes in late infancy.

Absorption↗

PubMed2002

Age and copper intake do not affect copper absorption, measured with the use of 65Cu as a tracer, in young infants.

BACKGROUND: Copper homeostasis involves a high degree of regulation in which changes in absorption and biliary excretion are the main mechanisms. Whether neonates and small infants can make these changes efficiently is unknown. OBJECTIVE: We evaluated the effect of age and copper intake on copper absorption in infants during the first 3 mo of life. DESIGN: Thirty-nine healthy infants (19 infants aged 1 mo and 20 infants aged 3 mo) were selected. One-half of the subjects were randomly assigned to receive oral supplementation of 80 mg Cu (as copper sulfate). kg body wt(-1). d(-1) for 15 d. At the end of the trial, copper absorption was measured by using orally administered (65)Cu as a tracer and fecal monitoring of recovered (65)Cu. RESULTS: Mean (+/- SD) copper absorption at 1 mo of age was 83.6 +/- 5.8% and 74.8 +/- 9.1% for the unsupplemented and supplemented infants, respectively. The corresponding figures at 3 mo of age were 77.6 +/- 15.2% and 77.7 +/- 11.3%. A two-way analysis of variance showed that age, copper supplementation, and the interaction between age and copper supplementation did not have a significant effect on copper absorption. There was an inverse correlation between total fecal copper and the percentage of (65)Cu absorption (r = -0.50, P < 0.003). CONCLUSION: Copper absorption in young infants is high but does not respond to copper intake within the range tested.

Aging↗

PubMed2002

Alpha(1)-antitrypsin and antichymotrypsin in human milk: origin, concentrations, and stability.

BACKGROUND: The protease inhibitors alpha(1)-antitrypsin and antichymotrypsin are present in human milk, but little is known about their roles in protein digestion during infancy. It has been hypothesized that alpha(1)-antitrypsin and antichymotrypsin may modulate digestion in the infant gut. OBJECTIVE: We determined whether the mammary gland expresses alpha(1)-antitrypsin and antichymotrypsin, measured alpha(1)-antitrypsin and antichymotrypsin throughout lactation, assessed the resistance of alpha(1)-antitrypsin to proteolysis, and determined the potential of alpha(1)-antitrypsin to affect the survival of other milk proteins. DESIGN: A pool of complementary DNA from the human mammary gland was analyzed with polymerase chain reaction to detect genes for alpha(1)-antitrypsin and antichymotrypsin. alpha(1)-Antitrypsin and antichymotrypsin concentrations were measured in milk samples obtained longitudinally (days 4-47) from 8 women. An in vitro model of infant digestion was used to assess the digestive stability of alpha(1)-antitrypsin against pepsin and pancreatin. Lactoferrin, with alpha(1)-antitrypsin present, was digested by pancreatin, and the digested proteins were separated. RESULTS: Alpha(1)-antitrypsin and antichymotrypsin concentrations were high in early milk and decreased throughout lactation. Polymerase chain reaction products were detected for both genes. After in vitro digestion, much of the alpha(1)-antitrypsin was still intact, whereas many other milk proteins were digested. Much of the lactoferrin was still intact after digestion, but only when alpha(1)-antitrypsin was added. CONCLUSIONS: The results suggest that alpha(1)-antitrypsin and antichymotrypsin are produced by the mammary gland and are present in milk in relatively high amounts in early lactation. alpha(1)-Antitrypsin may survive digestion and may affect the survival of other proteins.

Breast↗

PubMed2002

Iron status of infants fed low-iron formula: no effect of added bovine lactoferrin or nucleotides.

BACKGROUND: The appropriate level of iron fortification in infant formula remains undetermined. OBJECTIVES: We compared hematologic indexes and iron-status indicators in infants who were either breast-fed or fed formula with concentrations of 2 or 4 mg Fe/L and evaluated the effects of providing part of the iron as bovine lactoferrin and of adding nucleotides. DESIGN: Healthy term infants were exclusively breast-fed (n = 16) or fed formula (n = 10-12) from age 4 +/- 2 wk to 6 mo. Anthropometric measures were taken monthly, and blood samples were taken at 1, 4, and 6 mo. Hematologic indexes; indicators of iron, zinc, and copper status; and erythrocyte fatty acids were assessed. RESULTS: No significant differences in hematology or iron status were observed between groups at 4 and 6 mo of age. Although 34% of all infants had a hemoglobin concentration <110 g/L at 6 mo, the absence of iron deficiency or defective erythropoiesis suggests that this hemoglobin cutoff is too high for this age group. Neither the source or the concentration of iron in formula nor fortification with nucleotides had any significant effect on serum zinc or copper, and nucleotide fortification did not affect erythrocyte fatty acids. CONCLUSIONS: A concentration of 1.6 mg Fe/L formula meets the iron requirement of healthy term infants aged </=6 mo, and providing more iron does not benefit iron stores. Fortification with bovine lactoferrin or nucleotides did not benefit either iron status or erythrocyte fatty acids. Additional studies are needed to establish age-appropriate cutoffs for iron deficiency and iron deficiency anemia in infancy.

Animals↗

PubMed2002

Efficacy and trial effectiveness of weekly and daily iron supplementation among pregnant women in rural Bangladesh: disentangling the issues.

BACKGROUND: According to our current understanding, iron absorption with weekly iron supplements is not higher than that with daily supplements (ie, there is no mucosal block). However, community-based trials have repeatedly shown that a weekly regimen is as effective as a daily one. Furthermore, when differences in absorption are found, they are commonly smaller than would be expected on the basis of differences in the amount of iron provided. The possibility of differential compliance between the regimens needs to be evaluated to explain these findings. OBJECTIVE: Taking compliance into account, we compared the efficacy and trial effectiveness of weekly and daily iron supplementation during pregnancy. DESIGN: In Bangladesh, 50 antenatal centers were randomly assigned to prescribe either 2 doses of 60 mg Fe once weekly or 1 dose of 60 mg Fe/d. Compliance was monitored by using a pill bottle equipped with an electronic counting device. Hemoglobin concentrations were measured at baseline and after 4, 8, and 12 wk of supplementation. RESULTS: There was no differential effect per iron tablet between weekly and daily regimens. A 12-wk daily regimen (68% compliance) produced a small but significantly greater hemoglobin response than did the weekly regimen (104% compliance). The first 20 tablets consumed produced most of the effect; after 40 tablets, there was no further response. CONCLUSIONS: There was no evidence of a mucosal block in the daily regimen. Over 12 wk, 50% of the amount of iron in a daily regimen was sufficient for maximum hemoglobin effect. The weekly regimen provided a large part of this amount, explaining the limited difference in effect. It appears that the current international recommendation for iron supplementation in pregnancy is higher than necessary.

Adult↗

PubMed2002

Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras.

Iron supplements are often prescribed during infancy but their benefits and risks have not been well documented. We examined whether iron supplements affect growth or morbidity of breast-fed infants. Full-term infants in Sweden (n = 101) and Honduras (n = 131) were randomly assigned to three groups at 4 mo of age: 1) placebo from 4 to 9 mo; 2) placebo from 4 to 6 mo and iron supplements [1 mg/(kg. d)] from 6 to 9 mo; or 3) iron supplements from 4 to 9 mo. All infants were exclusively or nearly exclusively breast-fed to 6 mo and continued to be breast-fed to at least 9 mo. Growth was measured monthly and morbidity data were collected every 2 wk. Among the Swedish infants, gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo. The same effect on length was seen in Honduras, but only at 4-6 mo among those with initial hemoglobin (Hb) > or =110 g/L. There was no significant main effect of iron supplementation on morbidity, nor any significant interaction between iron supplementation and site, but for diarrhea (with both sites combined), there was an interaction between iron supplementation and initial Hb. Among infants with Hb < 110 g/L at 4 mo, diarrhea was less common among those given iron than in those given placebo from 4-9 mo, whereas the opposite was true among those with Hb > or = 110 g/L (P < 0.05). We conclude that routine iron supplementation of breast-fed infants may benefit those with low Hb but may present risks for those with normal Hb.

Anemia↗

PubMed2002

Zinc transporters in the rat mammary gland respond to marginal zinc and vitamin A intakes during lactation.

Marginal intake of zinc and vitamin A is common during lactation and a deficiency of one micronutrient can result in a secondary deficiency of the other. However, the resistance of milk zinc (Zn) concentration to changes in dietary Zn or vitamin A indicates tight regulation of mammary gland Zn transport. Although several mammalian proteins have been identified and implicated in Zn transport, the mechanisms responsible for mammary gland Zn transport and their regulation by dietary Zn and vitamin A are unknown. In this study, we identified mammary gland Zn transporters and determined effects of marginal Zn and vitamin A intakes on their levels. Rats were fed a control [25 mg Zn/kg, 4 retinol equivalents (RE)/g], a low Zn (10 mg Zn/kg), a low vitamin A (0.4 RE/g), or a low Zn (10 mg Zn/kg) and vitamin A (0.4 RE/g) diet throughout lactation. ZnT-1, ZnT-2 and ZnT-4 were identified in the mammary gland and localized to the serosal membrane (ZnT-1) or intracellularly (ZnT-2 and ZnT-4) by immunostaining. Rats fed a low Zn or low vitamin A diet had lower ZnT-1 protein and higher ZnT-4 mRNA expression and protein levels compared with controls. There was a significant interaction between dietary Zn and vitamin A on zinc transporter mRNA expression and protein levels. Although total mammary gland Zn was not affected, mammary gland metallothionein levels were lower in rats fed low Zn and higher in rats fed low vitamin A, suggesting different mechanisms regulating zinc transporter levels. These results indicate that milk Zn level is maintained through coordinated regulation of mammary gland zinc transporters and documents an effect of vitamin A on zinc homeostasis at the molecular level during lactation.

Animals↗

PubMed2002

The diagnostic criteria for iron deficiency in infants should be reevaluated.

Diagnostic criteria for iron deficiency (ID) and iron deficiency anemia (IDA) in infants are poorly defined. Our aim was to establish appropriate cut-off values for hemoglobin (Hb), plasma ferritin, erythrocyte mean cell volume (MCV), zinc protoporphyrin (ZPP) and soluble transferrin receptors (TfR) in infancy. Exclusively breast-fed infants (n = 263) in Honduras and Sweden were randomly assigned to receive iron supplementation or placebo, and blood samples were obtained at 4, 6 and 9 mo of age. Reference ranges were determined using three different approaches for defining iron-replete infants. The usefulness of several variables for predicting the Hb response to iron was evaluated. We found the following 2 SD cut-off values in iron-replete infants: Hb <105 g/L at 4-6 mo and <100 g/L at 9 mo; ZPP >75 micro mol/mol heme at 4-6 mo and >90 micro mol/mol heme at 9 mo; ferritin <20 micro g/L at 4 mo, <9 micro g/L at 6 mo and <5 micro g/L at 9 mo; and TfR >11 mg/L at 4-9 mo. The Hb response to iron was not a useful definition of IDA at 4 mo of age. Hb, MCV and ZPP at 6 mo as well as growth variables predicted the Hb response at 6-9 mo, but ferritin and TfR at 6 mo did not. We conclude that there is need for a reevaluation of the definitions of ID and IDA in infants.

Anemia, Iron-Deficiency↗

PubMed2002

Supplementation of infant formula with the probiotic lactobacillus reuteri and zinc: impact on enteric infection and nutrition in infant rhesus monkeys.

UNLABELLED: Gut colonization by may have beneficial effects on infant health or capacity to resist infectious disease. Zinc supplementation has also been proposed to increase infants' resistance to disease; however, many studies have yielded conflicting results. OBJECTIVES: To study effects of probiotic supplementation of infant formula (with or without supplemental zinc) on nutritional status, gut colonization and the ability to resist gastrointestinal infection in an infant rhesus monkey model. METHODS: Infant monkeys were fed control infant formula (5 mg Zn/L), control formula with or control formula with and supplemental zinc (15 mg Zn/L) from birth to 4 months. Growth, nutritional status, mineral absorption, intestinal colonization and frequency and severity of enteropathogenic -induced gastroenteritis were monitored. RESULTS: Gastrointestinal colonization was achieved and was associated with increased ileal villous surface area and improved hematocrit, with no adverse effects on growth or nutritional indices. Fortification to 15 mg Zn/L reduced plasma copper, erythrocyte Cu/Zn-superoxide dismutase, hemoglobin, and iron absorption. Infants fed -supplemented formula had reduced diarrhea severity throughout the study period and recovered more rapidly from acute diarrhea than the other groups. CONCLUSION: -supplementation of infant formula is safe, improves iron status and decreases diarrhea severity in infant rhesus monkeys and thus may help protect formula-fed human infants from infection and nutritional deficiencies.

Animals↗

PubMed2002

Mechanisms of vitamin B(12) absorption in breast-fed infants.

OBJECTIVES: The mechanisms of vitamin B(12) absorption in infants are unknown. We investigated whether haptocorrin (HC), a vitamin B(12) -binding protein in human milk, facilitates vitamin B(12) absorption during the neonatal period or if it occurs by a process similar to that in adults involving another vitamin B(12) -binding protein, intrinsic factor (IF). METHODS: To determine whether HC or IF can deliver vitamin B(12) to the enterocyte, binding studies using Caco-2 intestinal cells in culture and purified human milk HC-[ (57)Co]vitamin B(12) or [(125)I]IF-vitamin B(12) were performed. Determination of IF secretion by infant stomach was investigated by a competitive ELISA on fecal extracts from breast-fed infants. Determination of receptors specific for IF-vitamin B(12) or HC-vitamin B(12) in infant intestine was achieved by ligand blot analysis using isolated brush border membrane vesicles (BBMV) from fetal and adult intestine and Caco-2 cells. PCR was performed to identify the IF receptor gene transcript in Caco-2 cells and fetal intestine. RESULTS: Limited binding of both HC and IF to Caco-2 cells was observed; however, HC displayed affinity to low molecular weight proteins in BBMV from fetal intestine and Caco-2 cells while IF showed affinity for a 240 kDa protein in BBMV from fetal intestine and Caco-2 cells. IF receptor gene transcript was identified in fetal intestine and Caco-2 cells. An increase in IF excretion from breast-fed infants throughout early life was observed. CONCLUSIONS: An IF-dependent vitamin B(12) absorption mechanism appears to be in place in breast-fed infants. However, IF levels may be too low in early life to participate in vitamin B(12) absorption; therefore, haptocorrin may mediate vitamin B(12) absorption until the absorption function can be taken over by a more mature IF system.

Asialoglycoprotein Receptor↗