Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula

Many infant formulas are fortified with iron at 8–14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf−) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 µg/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status.

Download Full-text

Iron fortification of infant formula

Nutrition Research Reviews ◽

10.1079/095442200108729070 ◽

2000 ◽

Vol 13 (2) ◽

pp. 215-227 ◽

Cited By ~ 10

Author(s):

R. J. D Moy

Keyword(s):

Clinical Trials ◽

Adverse Effects ◽

Immune Function ◽

Infant Formula ◽

Safety Net ◽

Fe Deficiency ◽

Bovine Lactoferrin ◽

Fe Content ◽

The Usa ◽

Made In

AbstractThe purpose of this review is to examine the need for and appropriate level of Fe fortification of infant formula, and to assess any adverse effects of Fe fortification. The appropriate level of Fe fortification of infant formula has been established through studies of Fe absorption or erythrocyte incorporation of Fe, and through clinical trials of formulas with varying levels of Fe that were aimed at preventing the development of Fe deficiency in participating infants. In addition, the effects of varying levels of Fe fortification on the absorption of other minerals and trace elements, and on the incidence of infection and immune function have been studied, as has the effect of adding bovine lactoferrin to formula. Studies of Fe absorption have shown that increasing the level of Fe fortification in formula does not significantly increase the amount absorbed, and that the addition of bovine lactoferrin is unlikely to further increase absorption of Fe. Quite different recommendations for the level of Fe fortification of formula are made in the USA and in Europe. The higher level (12 mg/l) commonly used in the USA is not well supported by the evidence from clinical trials that suggest that lower levels (4 mg/l or less) may be adequate to prevent the development of Fe deficiency. Higher levels of Fe fortification may also interfere with the absorption of other minerals such as Cu and Se. Concerns about potential adverse effects of Fe fortification on immune function and susceptibility to infections have been disproved as have concerns about associated gastrointestinal symptomatology. There are no clearly demonstrated advantages in using ‘follow-on’ formula with high Fe content (up to 13 mg/l) instead of the standard UK formulas with Fe fortification in the range 4–7 mg/l after the age of 6 months, although they may provide an important ‘safety net’ for the prevention of Fe deficiency in communities with weaning diets low in Fe.

Download Full-text

Determination of bovine lactoferrin in infant formula by capillary electrophoresis with ultraviolet detection

Journal of Chromatography A ◽

10.1016/j.chroma.2012.05.004 ◽

2012 ◽

Vol 1244 ◽

pp. 178-183 ◽

Cited By ~ 15

Author(s):

Jia Li ◽

Xiaojing Ding ◽

Yongyan Chen ◽

Baohua Song ◽

Shan Zhao ◽

...

Keyword(s):

Capillary Electrophoresis ◽

Infant Formula ◽

Bovine Lactoferrin ◽

Ultraviolet Detection

Download Full-text

Determination of bovine lactoferrin in lactoferrin-supplemented dairy products and raw milk by an automated latex assay

Journal of Dairy Research ◽

10.1017/s0022029906002081 ◽

2006 ◽

Vol 74 (1) ◽

pp. 100-105 ◽

Cited By ~ 4

Author(s):

Takashi Soejima ◽

Koji Yamauchi ◽

Tomoko Yamamoto ◽

Yasuko Ohara ◽

Eiji Nagao ◽

...

Keyword(s):

Infant Formula ◽

Dairy Products ◽

Standard Addition ◽

Raw Milk ◽

Bovine Lactoferrin ◽

Addition Method ◽

Intermediate Precision ◽

Uht Milk ◽

Agglutination Method

Latex immune agglutination method with a multipurpose auto-analyser (the automated latex assay) was validated for determination of bovine lactoferrin (BLF) in various dairy products. Reproducibility-within-laboratory (intermediate precision) due to day for infant formula, UHT milk and yogurt supplemented with BLF at 50 mg/100 g for infant formula and UHT milk, and at 100 mg/100 g for yogurt were 1·62 to 3·10 mg/100 g. Reproducibility-within-laboratory due to analysis (morning, noon, and evening) for raw milk was 1·59 mg/100 g. Trueness, accuracy in determining known amounts added for BLF-supplemented dairy products was −4·7 to −2·0 mg/100 g. BLF concentration in raw milks was 20·3 to 21·8 mg/100 g. Although interference by the matrixes took place in infant formula and raw milk, BLF assays were accurately carried out by 2000-fold dilution or standard-addition method. Automated latex assay for BLF is simple, rapid, precise and accurate enough for a routine method in various dairy products containing BLF.

Download Full-text

Iron Availability from an Infant Formula Supplemented with Bovine Lactoferrin

Acta Paediatrica ◽

10.1111/j.1651-2227.1991.tb11826.x ◽

1991 ◽

Vol 80 (2) ◽

pp. 155-158 ◽

Cited By ~ 37

Author(s):

G. SCHULZ-LELL ◽

K. DÖRNER ◽

H.-D. OLDIGS ◽

E. SIEVERS ◽

J. SCHAUB

Keyword(s):

Infant Formula ◽

Bovine Lactoferrin ◽

Iron Availability

Download Full-text

Bovine lactoferrin and lactoferricin derived from milk: production and applications

Biochemistry and Cell Biology ◽

10.1139/o01-230 ◽

2002 ◽

Vol 80 (1) ◽

pp. 109-112 ◽

Cited By ~ 131

Author(s):

M Tomita ◽

H Wakabayashi ◽

K Yamauchi ◽

S Teraguchi ◽

H Hayasawa

Keyword(s):

Immune System ◽

Infant Formula ◽

Cheese Whey ◽

Skim Milk ◽

Hydrophobic Interaction Chromatography ◽

Bovine Lactoferrin ◽

Functional Domain ◽

Pepsin Digestion ◽

Repeated Dose Toxicity ◽

Biological Actions

Bovine lactoferrin is produced on an industrial scale from cheese whey or skim milk. The safety of purified lactoferrin has been confirmed from the results of a reverse mutation test using bacteria, a 13-week oral repeated-dose toxicity study in rats, and clinical studies. In order to apply active lactoferrin to various products, a process for its pasteurization was developed. Subsequently, lactoferrin has been used in a wide variety of products since it was first added to infant formula in 1986. A pepsin hydrolysate of lactoferrin is also used in infant formula. This hydrolysate contains a potent antimicrobial peptide named lactoferricin that is derived from the lactoferrin molecule by pepsin digestion. Semilarge-scale purification of lactoferricin can be performed by hydrophobic interaction chromatography. Lactoferricin also exhibits several biological actions and appears to be the functional domain of lactoferrin. Recent studies have demonstrated that oral administration of lactoferrin or lactoferricin exerts a host-protective effect in various animals and in humans. The results of these studies strongly suggest that the effects of oral lactoferrin are mediated by modulation of the immune system. Further elucidation of the clinical efficacy and mechanism of action of lactoferrin will increase the value of lactoferrin-containing products.Key words: bovine, lactoferrin, lactoferricin.

Download Full-text