Cow Milk-based Infant Formula Research Articles

Childhood Constipation: Is There New Light in The Tunnel?

IntroductionConstipation is a common phenomenon in childhood worldwide. The symptoms vary from mild and short-lived to severe and chronic with faecal impaction and encopresis. Although our understanding of pathophysiology has grown rapidly in recent decades, the causes and management of constipation

Lower Calcium Absorption in Infants Fed Casein Hydrolysate- and Soy Protein-Based Infant Formulas Containing Palm Olein Versus Formulas without Palm Olein

Objective: Quantitative balance studies were performed to compare fat and calcium absorption in healthy, full term infants fed casein hydrolysate-based (CHF) and soy protein-based (SPF) infant formulas with or without palm olein (PO). Previous studies have reported that PO significantly reduced absorption of both fat and calcium in cow’s milk-based formulas in which most of the calcium is inherent in the milk protein. In both SPF and CHF virtually all calcium is added as calcium salts.Methods: Two randomized, blinded, crossover balance studies were conducted in normal term infants using a three-day home balance method. One study evaluated 10 infants fed commercially available CHF with or without PO, and the other study evaluated 12 infants fed commercially available SPF with or without PO. Fat and calcium absorption were determined based on the weight of formula intake, weight of stools, and measured calcium and fat in formula and stools.Results: Fat and calcium intake did not differ between the groups fed CHF. However, infant’s calcium and fat absorption was less, 41 ± 6% (Mean ± SEM) and 92.0 ± 0.8%, respectively, when fed CHF with PO compared to 66 ± 5% and 96.6 ± 1.1%, respectively, when fed CHF without PO, (p < 0.01). For infants fed SPF, fat and calcium intake did not differ between the feeding groups. Mean calcium absorption was also significantly less when infants were fed SPF with PO, 22 ± 3%, than when fed SPF with no PO, 37 ± 4% (p < 0.05). Fat absorption did not differ between the two SPFs.Conclusion: This study demonstrates that PO, as the predominant fat, is associated with significantly lower absorption of calcium from infant formulas in which calcium salts are the source of calcium. These findings corroborate previous reports of this negative effect of PO in cow milk-based infant formulas in which most of the calcium is a component of the cow milk protein source.

Cow's milk and immune-mediated diabetes.

Cow's milk-based infant formulas and cow's milk consumption in childhood have been suggested to promote the development of type 1 diabetes mellitus and other immune-mediated or neurological diseases. Epidemiological studies in man have led to the hypothesis that introduction of cow's milk-based infant formula within the first 3 months of life is associated with increased risk of type 1 diabetes mellitus. Furthermore, in animal models of type 1 diabetes mellitus, cow's milk proteins have been proven to be 'diabetogenic'. However, the issue seems far from being resolved. Several epidemiological studies and, more importantly, the first prospective trials did not show an association between early exposure to cow's milk and type 1 diabetes mellitus. In animal models, cow's milk proteins are modestly and variably diabetogenic, wheat or soybean proteins in the diet cause higher rates of autoimmune diabetes. In both man and rodents there is increasing evidence that the gut-associated immune system plays a major role in disease development, probably because of disturbed oral tolerance mechanisms. Oral tolerance depends on immunological homeostasis and normal maturation of the gut. These factors are influenced by growth factors and cytokines from breast milk, normal bacterial colonization, infections and diet. All these factors have been proposed as risk factors for type 1 diabetes mellitus. Hence, cow's milk proteins may provide mimicry epitopes relevant in autoimmunity, as well as destabilizing oral tolerance mechanisms by biologically active peptides. The concept of dietary regulation of autoimmunity does not apply only to cow's milk protein, but also to other dietary proteins.

Infant formula ingestion is associated with the development of diabetes in the BB/Wor rat

The association between early exposure to cow's milk products in infancy and risk for insulin dependent diabetes mellitus (IDDM) is controversial. We examined whether the ingestion of cow's milk-based infant formula altered the expression of the diabetic syndrome in the BB/Wor rat, an animal model of IDDM. Pregnant BB/Wor dams were obtained from the NIH contract colony at the University of Massachusetts and housed under semi-barrier conditions. Rat pups were intubated with 1 to 2 ml of commercially available cow's milk-based infant formula (Enfamil® or Nutramigen®) or sham intubated (controls) daily from day 12 to day 25 of life. Pups were weaned at day 25 and monitored for glucosuria daily through 120 days of life. All rats including dams consumed a milk-free rat chow and acidified water ad libitum throughout the study. The mean age of disease onset was 4 to 10 days earlier in Nutramigen®-fed and Enfamil®-fed rats relative to controls (84 ± 3, 78 ± 2 and 88 ± 4 days, respectively); the mean age of disease onset was significantly different between controls and Enfamil®-fed animals (p < 0.05). At 120 days, 60% (12/20) of control rats developed diabetes versus 100% of animals fed either type of infant formula prior to weaning (15/15:Enfamil®-fed; 19/19:Nutramigen®-fed) (p < 0.05). These data indicate that direct, early ingestion of cow's milk-based formula was related to the expression of diabetes in the BB/Wor rat.

Cow's-milk-based Infant Formula: Heterogeneity of Bovine Serum Albumin Content

Type 1 diabetes mellitus is a chronic autoimmune disease that results in destruction of the insulin-producing β-cells of the islets of Langerhans of the pancreas. Although 25% of the population carries genetic markers for type 1 diabetes, only 5% of those with genetic predisposition develop the disease (1). Genetic predisposition alone does not indicate progression to clinical disease; therefore, research has focused on identifying environmental determinants involved in the immunopathogenesis of type 1 diabetes.

Cow's milk and type I diabetes: the gut immune system deserves attention

Early introduction of cow's milk-based infant formula might be a major environmental factor in the development of immune-mediated (type 1) diabetes in humans. A recent meeting * * The Symposium ‘Cow's Milk and Diabetes’ was held at Barcelona, Spain, on 7 September 1998. proposed a critical role for gut immune reactivity in disease pathogenesis.

Analysis of Norwegian milk and infant formulas for ochratoxin A

Samples of organic cow's milk, conventional cow's milk, and cow's milk-based infant formulas were analysed for the occurrence of ochratoxin A by means of an HPLC method. The detection limit was 10ng/l. Ochratoxin A was detected in 6 out of 40 conventional cow's milk samples (range 11–58ng/l), and in 5 out of 47 organic milk samples (range 15–28ng/l). No ochratoxin A was detected in any of the 20 infant formula samples. The ochratoxin A levels in cow's milk found in this investigation are sufficient to cause a higher intake of ochratoxin A than the suggested TDI of 5ng/kg bw/ day, e.g. in small children who consume large quantities of milk.

Polyamines in human and rat milk influence intestinal cell growth in vitro.

Polyamines are required for intestinal growth and development. In this study, we examined whether milk can supply the polyamines needed for growth of IEC-6 cells, a line on non-transformed rat intestinal crypt cells. Human, bovine, and rat milk, and cow's milk-based infant formula were studied. Human, bovine, and rat milk were defatted and sterilized by filtration. IEC-6 cells were stabilized in Dulbecco's modified Eagle's medium (DMEM) containing 0.5% fetal bovine serum, 5 mM L-glutamine, 100 U/mL penicillin and 100 microg/mL streptomycin for 24 h at 37 degrees C. Thereafter, to initiate active growth, cells were placed in fresh DMEM containing 5% FBS (plus the other ingredients) supplemented with 5% (vol/vol) milk or infant formula. In some experiments, cells were also treated with difluoromethylornithine (2.5 mM) (DFMO), an inhibitor of polyamine synthesis, or dialyzed milk plus DFMO. After 44 hours of culture, cells were pulsed with 3H-thymidine (3H-TdR) for 4 hours, harvested and the radioactivity incorporated into DNA was measured. Human and rat milk stimulated proliferation of IEC-6 cells (p < 0.05 compared to controls); addition of DFMO did not reverse the stimulatory effect. Bovine milk and the infant formula did not stimulate proliferation or prevent the growth inhibition induced by DFMO. After dialysis, human milk had less ability to reverse the DFMO inhibition (p < 0.05). These experiments suggest that both human and rat milk, but neither bovine milk nor the infant formula, contain sufficient bioactive polyamines to sustain cell growth during inhibition of polyamine synthesis.

Calcium and phosphorus supplementation of iron-fortified infant formula: no effect on iron status of healthy full-term infants

One objective of this clinical trial was to determine whether calcium and phosphorus supplementation of infant formula affects the iron status of healthy full-term infants. One hundred three infants were randomly assigned to receive iron-fortified, cow milk-based infant formula (465 mg Ca and 317 mg P/L) or the same formula with added calcium glycerophosphate (1800 mg Ca and 1390 mg P/L) for 9 mo. Reported calcium intake for supplemented infants was about four times that of control infants, ranging from a mean of 1741 mg/d at baseline to 1563 mg/d at 9 mo. There was no difference by treatment group in mean or median change from baseline of serum ferritin, total-iron-binding capacity, erythrocyte protoporphyrin, or hematocrit at 4 and 9 mo after enrollment. Incidence of iron deficiency was similar for both groups and no infant developed iron deficiency anemia during the trial. This study indicates that the well-documented inhibitory effect of calcium and phosphorus on iron absorption is not clinically important in infants fed iron-fortified infant formula.

Intestinal oxygenation and mucosal permeability with luminal mother's milk in developing piglets.

We have previously observed a developmental difference in mucosal permeability (i.e. the younger the animal, the greater the increase in permeability) after exposure to luminal nutrients derived from cow's milk-based infant formulas. There has been tremendous speculation and some clinical evidence that mother's milk may be protective against mucosal injury in developing intestine. In this study, we hypothesized that instillation of sow's milk into the intestinal lumen of developing piglets would cause no differences in either intestinal metabolic demand (oxygen uptake) or mucosal permeability among age groups. Intestinal blood flow (total and fractionated), arteriovenous oxygen content difference, venous pressure, and capillary pressure were measured, and vascular resistance and oxygen uptake were calculated, after 30 min of intraluminal instillation of predigested and solubilized sow's milk in 1-d-old, 3-d-old, 2-wk-old, and 1-mo-old piglet jejunoileum. In a separate group of animals, plasma-to-lumen clearance of chromium-51 EDTA was evaluated during luminal perfusion with digested and solubilized sow's milk in 1-d-old, 3-d-old, and 1-mo-old piglet jejunoileum. Intestinal oxygen uptake was similar among age groups of developing piglets, but EDTA clearance was significantly higher for intestinal segments perfused with sow's milk in 1-d-old, compared with older, animals. Thus, luminal perfusion with predigested and bile acid-solubilized sow's milk in 1-d-old piglet jejunoileum, compared with perfusion in older piglets, causes increased mucosal permeability in 1-d-old intestine, but this increased permeability is not due to increased intestinal oxygen uptake (i.e. increased metabolic demand).

Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula.

At present, not much is known about the absorption and metabolism of human milk (HM) oligosaccharides in term and preterm infants. We investigated the renal excretion of lactose and complex oligosaccharides in preterm infants fed HM (n = 9, mean actual body weight 2290 g) or a cow's milk-based infant formula (n = 9, mean actual body weight 2470 g). We found that the renal excretion of lactose in HM-fed infants was slightly lower than in formula-fed infants (14.0 +/- 7.4 versus 20.4 +/- 8.7 mg kg-1 day-1, mean +/- SD). The excretion of neutral sugars deriving from oligosaccharides was similar in HM-fed and formula-fed infants (3.8 +/- 2.1 versus 2.9 +/- 0.9 mg kg-1 day-1); the difference between means was not statistically significant. The separation and characterization of oligosaccharides by high-pH anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) and subsequent analysis by fast atom bombardment-mass spectrometry (FAB-MS) revealed a more complex pattern in HM-fed infants compared to the formula-fed group. Lactose-derived oligosaccharides characteristic for HM (e.g. lacto-N-tetraose, and lacto-N-fucopentaoses I and II) were excreted in HM-fed but not in formula-fed infants. These results indicate that nutrition has a significant impact on the oligosaccharide composition in urine of preterm infants.

The significance of tryptophan in human nutrition

Aside from its role as one of the limiting essential amino acids in protein metabolism, tryptophan (TRP) serves as precursor for the synthesis of the neurotransmitters serotonin and tryptamine as well as for the synthesis of the antipellagra vitamin nicotinic acid and the epiphyseal hormone melatonin.By involvement in so manifold pathways, TRP and its metabolites regulate neurobehavioral effects such as appetite, sleeping-waking-rhythm and pain perception. TRP is the only amino acid which binds to serum albumin to a high degree. Its transport through cell membranes is competetrvely inhibited by large neutral amino acids (NAA). The TRP/NAA ratio in plasma is essential for the TRP availability and thus for the serotonin synthesis in the brain.Due to its high TRP-concentration, human milk protein provides optimal conditions for the availability of the neurotransmitter serotonin. Low protein cow's milk-based infant formulas supplemented withα-lactalbumin - a whey protein fraction containing 5.8% TRP - present themselves as a new generation of formulas, with an amino acid pattern different from the currently used protein mixtures of adapted formulas, resembling that of human milk to a much higher degree.

An animal model of necrotizing enterocolitis induced by infant formula and ischemia in developing piglets

Background/Aims: The lipid component of piglet formula (0.5% fat) causes increased mucosal permeability in 1-day-old piglets after ischemia/reperfusion. The present study examined if luminal exposure to infant formulas (3.5% fat) and ischemia/reperfusion result in an animal model of necrotizing enterocolitis and if injury is dependent on the formula fat composition. Methods: Plasma-to-lumen clearance of 51Cr-ethylenediaminetetraacetic acid was measured, and morphology was evaluated during luminal perfusion with preterm, term, and delipidated preterm cow milk-based infant formulas before and after ischemia/reperfusion in 1-day-old and 1-month-old piglet jejunoileum. In a separate set of experiments, a 1–2-cm segment of ileum was exteriorized and opened to expose the mucosal surface, and the villi were superfused with the above formulas (no ischemia). Results: Before ischemia, clearances were markedly higher for intestinal loops perfused with preterm formula than for loops perfused with term and delipidated formulas in 1-day-old animals. After ischemia, clearances in loops perfused with preterm formula were significantly greater and grossly hemorrhagic and historically necrotic compared with loops perfused with delipidated formula (minimal injury). Superfusion with preterm formula caused diffuse hyperemia and hemorrhage into intestinal villi. Conclusions: Luminal perfusion of 1-day-old piglet jejunoileum with predigested and bile acid-solubilized preterm infant formula, in combination with ischemia/reperfusion, produces an animal model of necrotizing enterocolitis, but only if the lipid fraction of the formula is present.

Comparative metabolic study of older infants fed infant formula, transition formula, or whole cow's milk

“Transition” or “follow-up” formulas are formulas distinct in composition from “starter” infant formulas and are used in feeding infants six months of age or older. We have performed metabolic balance studies in nine children between the ages of six and nine months using a randomized double blind cross- over design. Three diets were fed: a cow's milk-based “follow-up” formula (FUF), a standard cow's milk-based infant formula (IF), or whole cow's milk (WCM). Weight gain (g/day) was equivalent among the three groups. Fecal excretion of energy was higher on WCM than on the other two diets, with the only significant difference being between WCM and IF. Fecal excretion of fat was greater on WCM and FUF than IF (20.4%, 17.8%, and 8.4% respectively). Carbohydrate excretion and nitrogen retention were similar on all 3 formulas. Although always normal, serum albumin significantly decreased at the end of the FUF dietary period. Urine osmolality was abnormally high during the WCM period, but always within normal limits while on FUF or IF. Within the context of this study, the FUF had metabolic advantages when compared to WCM but not to the IF.

Nonclinical testing of formulas containing hydrolyzed milk protein

The allergenic potential of cow milk-based infant formula can be reduced by protein hydrolysis. Controlled clinical studies are necessary to demonstrate conclusively the biologic efficacy of these formulations in human beings. Nonclinical testing programs provide manufacturers with the opportunity to characterize various molecular and immunologic properties of these hydrolysates and their corresponding final product forms. Physicochemical analyses provide data relating to the extent of protein hydrolysis and peptide molecular weight distribution. Immunochemical analyses can semiquantitatively estimate hydrolysate reactivity with preformed antibody. The ability of hydrolysate-based products to induce an immune response can be evaluated by using animal models. It is the responsibility of the manufacturer to choose the appropriate combination of nonclinical tests and use them to document product consistency, thus helping to ensure consistent clinical performance.

Human Breast Milk Contains Bovine lgG. Relationship to Infant Colic?

Previous studies have suggested that an unidentified cow's milk protein, other than β-lactoglobulin and casein, might play a pathogenetic role in infant colic. Therefore, a radioimmunoassay was used to analyze human breast milk and infant formula samples for the presence of bovine IgG. Milk samples from 88 of the 97 mothers tested contained greater than 0.1 µg/mL of bovine IgG. In a study group of 59 mothers with infants in the colic-prone 2- to 17-week age group, the 29 mothers of colicky infants had higher levels of bovine IgG in their breast milk (median 0.42 µg/mL) than the 30 mothers of noncolicky infants (median 0.32 µg/mL) (P &amp;lt; .02). The highest concentrations of bovine IgG observed in human milk were 8.5 and 8.2 µg/mL. Most cow's milk-based infant formulas contained 0.6 to 6.4 µg/mL of bovine IgG, a concentration comparable with levels found in many human milk samples. The results suggest that appreciable quantities of bovine IgG are commonly present in human milk, that significantly higher levels are present in milk from mothers of colicky infants, and that bovine IgG may possibly be involved in the pathogenesis of infant colic.