Bovine lactoferrin in infant formula

Bovine lactoferrin in infant formula

This summary is adapted from Growth and tolerance of formula with lactoferrin in infants through one year of age: double-blind, randomized, controlled trial by Johnston et al
This study sought to investigate the addition of bovine lactoferrin as an additive to infant formula. Lactoferrin is an iron-binding protein that is present in human breast milk and has a wide range of function in the body. Involved in the regulation of gene expression, it affects iron status maintenance along with modulating the immune system to encourage healthy host defense systems against disease-causing organisms1. It is made by cells present in the mammary glands and is therefore secreted into breastmilk. Lactoferrin can be absorbed from breast milk into the bloodstream in the gastrointestinal tract. The human form of lactoferrin has been seen to be similar both structurally and functionally to bovine lactoferrin2. However, there is only a very small amount of bovine lactoferrin present in natural cow’s milk, therefore current cow’s milk formulations for infants do not contain a significant amount. Some small previous studies have looked at increasing the concentration of bovine lactoferrin in cow’s milk infant formula3,4,5,6. In full term infants, this was found to be safe, associated with normal growth rate, and give a lower incidence of some infections, likely due to the immune modulation effects. It also reduced the incidence and frequency of vomiting and diarrhea5. This was mirrored in a study conducted in preterm infants6. However, these studies were small and a large sample size was needed to confirm some of these effects. This was the aim of the study described here. In addition to bovine lactoferrin, this trial aimed to investigate some other potentially beneficial compounds as additives to cow’s milk formula. Human milk oligosaccharides are compounds normally present in human breast milk, again have been found to have an immune modulating effect to encourage host defense. In addition, they aid in softening the stool of infants7. Prebiotics are often added to infant formula to mimic their effects as they act in a similar manner. This study investigated the specific prebiotic combination of polydextrose, galactooligosaccharides, and adjusted arachidonic acid. The rationale for this combination was based on a previous study which showed this combination added to cow’s milk infant formula led to normal growth rates and softer stool in preterm infants. Another interesting effect of both this prebiotic combination and lactoferrin is the alteration of the microbiome. In health infants, the prebiotic combination produced a gastrointestinal tract microbiome closer to that seen with breastfeeding compared to standard formula8. Lactoferrin was also seen to affect the gastrointestinal tract microbiome in low-birth-weight infants, although not in a similar way to human breast milk. This larger scale clinical trial of the addition of both lactoferrin and a specific combination of prebiotics was designed to investigate the safety of this formula and potential benefits. The concentration of lactoferrin used here in the cow’s milk formula was similar to what is found in human breast milk, potentially maximizing its benefit. There were 480 infants enrolled in this study, which included 155 in the control group receiving a marketed cow’s milk-based infant formula, and 325 receiving two slightly different concentrations of bovine lactoferrin and the prebiotic blend added to the cow’s milk formula. This trial ran from day 14 after birth to day 365, with 353 infants completing the trial. The infants included were full-term (37-42 weeks), normal weight, with no history of underlying disease, infection/immunodeficiency, formula intolerance or weight loss since birth. The main aim of the study was investigation of weight/growth rate from 14-120 days post birth. Secondary aims included body weight, length, head circumference, formula intake, tolerance, stool characteristics and adverse events. Immune system related effects were not investigated. The results that were reported in this study found no differences in the main aim, growth rate between 14-120 days, between the standard cow’s milk formula and the formula with additives. Little difference was also seen in the secondary aims. There were no differences across the groups in adverse events, growth measures, tolerance as measured by fussiness and gassiness, formula intake and stool frequency. In fact, the only statistically and clinically significant difference was a softer stool consistency in those who received the lactoferrin and prebiotic additive formula compared to control. This difference was only seen in days 30-180, potentially due to the normal increase in feeding and the decrease in formula intake in the infants at this time. From these results we can conclude that the addition of bovine lactoferrin and the specific combination of prebiotics to cow’s milk formula is safe and does not affect the growth of infants. Many of the outcomes such as tolerance and stool characteristics were collected via parent recall, which may have limited the ability to specifically detect differences between the study groups as this is an imprecise measurement. There may be some potential benefits of the additive study formula that were not studied in this trial, such as the aforementioned immune system modulation and microbiome alteration effects. Investigating these areas could clarify whether these substances should be added to standard cow’s milk formula.
References:
  1. Ward, P.P., Paz, E.U.G.E.N.E. and Conneely, O.M., 2005. Lactoferrin. Cellular and molecular life sciences, 62(22), pp.2540-2548.
  2. Tomita, M., Wakabayashi, H., Shin, K., Yamauchi, K., Yaeshima, T. and Iwatsuki, K., 2009. Twenty-five years of research on bovine lactoferrin applications. Biochimie, 91(1), pp.52-57.
  3. King Jr, J.C., Cummings, G.E., Guo, N., Trivedi, L., Readmond, B.X., Keane, V., Feigelman, S. and de Waard, R., 2007. A double-blind, placebo-controlled, pilot study of bovine lactoferrin supplementation in bottle-fed infants. Journal of pediatric gastroenterology and nutrition, 44(2), pp.245-251.
  4. Ochoa, T.J., Chea-Woo, E., Campos, M., Pecho, I., Prada, A., McMahon, R.J. and Cleary, T.G., 2008. Impact of lactoferrin supplementation on growth and prevalence of Giardia colonization in children. Clinical infectious diseases, 46(12), pp.1881-1883.
  5. Egashira, M., Takayanagi, T., Moriuchi, M. and Moriuchi, H., 2007. Does daily intake of bovine lactoferrin‐containing products ameliorate rotaviral gastroenteritis?. Acta Paediatrica, 96(8), pp.1242-1244.
  6. Manzoni, P., Stolfi, I., Messner, H., Cattani, S., Laforgia, N., Romeo, M.G., Bollani, L., Rinaldi, M., Gallo, E., Quercia, M. and Maule, M., 2012. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial. Pediatrics, 129(1), pp.116-123.
  7. Ziegler, E., Vanderhoof, J.A., Petschow, B., Mitmesser, S.H., Stolz, S.I., Harris, C.L. and Berseth, C.L., 2007. Term infants fed formula supplemented with selected blends of prebiotics grow normally and have soft stools similar to those reported for breast-fed infants. Journal of pediatric gastroenterology and nutrition, 44(3), pp.359-364.
  8. Scalabrin, D.M., Mitmesser, S.H., Welling, G.W., Harris, C.L., Marunycz, J.D., Walker, D.C., Bos, N.A., Tölkkö, S., Salminen, S. and Vanderhoof, J.A., 2012. New prebiotic blend of polydextrose and galacto-oligosaccharides has a bifidogenic effect in young infants. Journal of pediatric gastroenterology and nutrition, 54(3), pp.343-352.
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