1,069
Views
9
CrossRef citations to date
0
Altmetric
Review Articles

The application of lactoferrin in infant formula: The past, present and future

, , , , , , , , & show all

References

  • Abe, H., H. Saito, H. Miyakawa, Y. Tamura, S. Shimamura, E. Nagao, and M. Tomita. 1991. Heat stability of bovine lactoferrin at acidic pH. Journal of Dairy Science 74 (1):65–71. doi: 10.3168/jds.S0022-0302(91)78144-7.
  • Adams-Chapman, I. 2012. Long-term impact of infection on the preterm neonate. Seminars in Perinatology 36 (6):462–70. doi: 10.1053/j.semperi.2012.06.009.
  • Akin, I. M., B. Atasay, F. Dogu, E. Okulu, S. Arsan, H. D. Karatas, A. Ikinciogullari, and T. Turmen. 2014. Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells. American Journal of Perinatology 31 (12):1111–20. doi: 10.1055/s-0034-1371704.
  • Aly, E., G. Ros, and C. Frontela. 2013. Structure and functions of lactoferrin as ingredient in infant formulas. Journal of Food Research 2 (4):25–36. doi: 10.5539/jfr.v2n4p25.
  • An, J., Y. Xu, Z. Kong, Y. Xie, D. Tabys, M. Ma, X. Cao, H. Ren, and N. Liu. 2019. Effect of lactoferrin and its digests on differentiation activities of bone mesenchymal stem cells. Journal of Functional Foods 57:202–10. doi: 10.1016/j.j.2019.04.020.
  • Andersson, J., and B. Mattiasson. 2006. Simulated moving bed technology with a simplified approach for protein purification: Separation of lactoperoxidase and lactoferrin from whey protein concentrate. Journal of Chromatography A 1107 (1-2):88–95. doi: 10.1016/j.chroma.2005.12.018.
  • Andersson, Y., M.-L. Hammarström, B. Lönnerdal, G. Graverholt, H. Fält, and O. Hernell. 2009. Formula feeding skews immune cell composition toward adaptive immunity compared to breastfeeding. Journal of Immunology (Baltimore, Md.: 1950) 183 (7):4322–8. doi: 10.4049/jimmunol.0900829.
  • Andrés, M. T., M. Acosta-Zaldívar, and J. F. Fierro. 2016. Antifungal mechanism of action of lactoferrin: Identification of H+-ATPase (P3A-type) as a new apoptotic-cell membrane receptor. Antimicrobial Agents and Chemotherapy 60 (7):4206–16. doi: 10.1128/AAC.03130-15.
  • Andrés, M. T., M. Viejo-Díaz, and J. F. Fierro. 2008. Human lactoferrin induces apoptosis-like cell death in Candida albicans: Critical role of K+-channel-mediated K+ efflux. Antimicrobial Agents and Chemotherapy 52 (11):4081–8. doi: 10.1128/AAC.01597-07.
  • Anghel, L., A. Radulescu, and R. V. Erhan. 2018. Structural aspects of human lactoferrin in the iron-binding process studied by molecular dynamics and small-angle neutron scattering. The European Physical Journal 41:133. doi: 10.1140/epje/i2018-11720-x.
  • Axelsson, I., I. Jakobsson, T. Lindberg, S. Polberger, B. Benediktsson, and N. Raiha. 1989. Macromolecular absorption in preterm and term infants. Acta Paediatrica Scandinavica 78 (4):532–7. doi: 10.1111/j.1651-2227.1989.tb17932.x.
  • Baker, E. N., and H. M. Baker. 2009. A structural framework for understanding the multifunctional character of lactoferrin. Biochimie 91 (1):3–10. doi: 10.1016/j.biochi.2008.05.006.
  • Ballard, O., and A. L. Morrow. 2013. Human milk composition: Nutrients and bioactive factor. Pediatric Clinics of North America 60 (1):49–74. doi: 10.1016/j.pcl.2012.10.002.
  • Banavara, D., J. D. Alvey, J. A. Peters, and J. M. Gonzales. 2019. Expanded bed adsorption methods for isolation of basic milk proteins including lactoferrin. EP Patent 3,021,682 filed July 16, 2013, and issued April 20, 2017.
  • Barrington, K. J., M. A. Assaad, and A. Janvier. 2016. The Lacuna Trial: A double-blind randomized controlled pilot trial of lactoferrin supplementation in the very preterm infant. Journal of Perinatology: Official Journal of the California Perinatal Association 36 (8):666–9. doi: 10.1038/jp.2016.24.
  • Beljaars, L., B. Strate, H. I. Bakker, C. Reker-Smit, A. M. van Loenen-Weemaes, F. C. Wiegmans, M. C. Harmsen, G. Molema, and D. K. F. Meijer. 2004. Inhibition of cytomegalovirus infection by lactoferrin in vitro and in vivo. Antiviral Research 63 (3):197–208. doi: 10.1016/j.antiviral.2004.05.002.
  • Berkhout, B., R. Floris, I. Recio, and S. Visser. 2004. The antiviral activity of the milk protein lactoferrin against the human immunodeficiency virus type 1. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine 17 (3):291–4. doi: 10.1023/B:BIOM.0000027707.82911.be.
  • Björmsjö, M., O. Hernell, B. Lönnerdal, and S. K. Berglund. 2020. Reducing iron content in infant formula from 8 to 2 mg/L does not increase the risk of iron deficiency at 4 or 6 months of age: A randomized controlled trial. Nutrients 13 (1):3. doi: 10.3390/nu13010003.
  • Bode, L. 2018. Human milk oligosaccharides in the prevention of necrotizing enterocolitis: A journey from in vitro and in vivo models to mother-infant cohort studies. Frontiers in Pediatrics 6:385. doi: 10.3389/fped.2018.00385.
  • Bourlieu, C., O. Ménard, K. Bouzerzour, G. Mandalari, A. Macierzanka, A. R. Mackie, and D. Dupont. 2014. Specificity of infant digestive conditions: Some clues for developing relevant in vitro models. Critical Reviews in Food Science and Nutrition 54 (11):1427–57. doi: 10.1080/10408398.2011.640757.
  • Brock, J. H. 2002. The physiology of lactoferrin. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire 80 (1):1–6. doi: 10.1139/o01-212.
  • Buccigrossi, V., G. Marco, E. Bruzzese, L. Ombrato, I. Bracale, G. Polito, and A. Guarino. 2007. Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation. Pediatric Research 61 (4):410–4. doi: 10.1203/pdr.0b013e3180332c8d.
  • Carter, S. A., C. M. Parsons, S. M. Robinson, N. C. Harvey, K. A. Ward, C. Cooper, and E. M. Dennison. 2020. Infant milk feeding and bone health in later life: Findings from the Hertfordshire cohort study. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 31 (4):709–14. doi: 10.1007/s00198-020-05296-1.
  • Castanet, M., C. Costalos, N. Haiden, J.-M. Hascoet, B. Berger, N. Sprenger, D. Grathwohl, H. Brüssow, N. De Groot, P. Steenhout, et al. 2020. Early effect of supplemented infant formulae on intestinal biomarkers and microbiota: A randomized clinical trial. Nutrients 12 (5):1481. doi: 10.3390/nu12051481.
  • Chen, C. C., C. J. Chang, T. Y. Lin, M. W. Lai, H. C. Chao, and M. S. Kong. 2011. Usefulness of fecal lactoferrin in predicting and monitoring the clinical severity of infectious diarrhea. World Journal of Gastroenterology 17 (37):4218–24. doi: 10.3748/wjg.v17.i37.4218.
  • Chen, K., L. Chai, H. Li, Y. Zhang, H. M. Xie, J. Shang, W. Z. Tian, P. Yang, and A. C. Jiang. 2016. Effect of bovine lactoferrin from iron-fortified formulas on diarrhea and respiratory tract infections of weaned infants in a randomized controlled trial. Nutrition (Burbank, Los Angeles County, Calif.) 32 (2):222–7. doi: 10.1016/j.nut.2015.08.010.
  • Chen, K., S. Jin, H. Chen, Y. Cao, X. Dong, H. Li, Z. Zhou, and C. Liu. 2021. Dose effect of bovine lactoferrin fortification on diarrhea and respiratory tract infections in weaned infants with anemia: A randomized, controlled trial. Nutrition (Burbank, Los Angeles County, Calif.) 90:111288. doi: 10.1016/j.nut.2021.111288.
  • Chen, K., G. Zhang, H. Chen, Y. Cao, X. Dong, H. Li, and C. Liu. 2020. Dose effect of bovine lactoferrin fortification on iron metabolism of anemic infants. Journal of Nutritional Science and Vitaminology 66 (1):24–31. doi: 10.3177/jnsv.66.24.
  • Chen, K., L. Zhang, H. Li, Z. Ying, H. Xie, S. Jia, W. Tian, Y. Ping, L. Chai, and M. Meng. 2015. Iron metabolism in infants: Influence of bovine lactoferrin from iron-fortified formula. Nutrition (Burbank, Los Angeles County, Calif.) 31 (2):304–9. doi: 10.1016/j.nut.2014.07.006.
  • Chen, Y., B. Wang, C. Yang, Y. Shi, Z. Dong, and F. A. Troy. 2021. Functional correlates and impact of dietary lactoferrin intervention and its concentration‐dependence on neurodevelopment and cognition in neonatal piglets. Molecular Nutrition & Food Research 65 (8):2001099. doi: 10.1002/mnfr.202001099.
  • Chen, Y., Z. Zheng, X. Zhu, Y. Shi, D. Tian, F. Zhao, N. Liu, P. S. Huppi, F. A. Troy, and B. Wang. 2015. Lactoferrin promotes early neurodevelopment and cognition in postnatal piglets by upregulating the BDNF signaling pathway and polysialylation. Molecular Neurobiology 52 (1):256–69. doi: 10.1007/s12035-014-8856-9.
  • Chichlowski, M., N. Bokulich, C. L. Harris, J. L. Wampler, F. Li, C. L. Berseth, C. Rudolph, and S. S. Wu. 2021. Effect of bovine milk fat globule membrane and lactoferrin in infant formula on gut microbiome and metabolome at four months of age. Current Developments in Nutrition 5 (5):nzab027. doi: 10.1093/cdn/nzab027.
  • Comstock, S. S., E. A. Reznikov, N. Contractor, and S. M. Donovan. 2014. Dietary bovine lactoferrin alters mucosal and systemic immune cell responses in neonatal piglets. The Journal of Nutrition 144 (4):525–32. doi: 10.3945/jn.113.190264.
  • Conesa, C., C. Rota, E. Castillo, M. D. Perez, M. Calvo, and L. Sanchez. 2010. Effect of heat treatment on the antibacterial activity of bovine lactoferrin against three foodborne pathogens. International Journal of Dairy Technology 63 (2):209–15. doi: 10.1111/j.1471-0307.2010.00567.x.
  • Cooper, C. A., E. A. Maga, and J. D. Murray. 2015. Production of human lactoferrin and lysozyme in the milk of transgenic dairy animals: Past, present, and future. Transgenic Research 24 (4):605–14. doi: 10.1007/s11248-015-9885-5.
  • Cooper, C. A., K. M. Nelson, E. A. Maga, and J. D. Murray. 2013. Consumption of transgenic cows’ milk containing human lactoferrin results in beneficial changes in the gastrointestinal tract and systemic health of young pigs. Transgenic Research 22 (3):571–78. doi: 10.1007/s11248-012-9662-7.
  • Cornish, J., and D. Naot. 2010. Lactoferrin as an effector molecule in the skeleton. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine 23 (3):425–30. doi: 10.1007/s10534-010-9320-6.
  • Dong, Y., and C. P. Speer. 2015. Late-onset neonatal sepsis: Recent developments. Archives of Disease in Childhood. Fetal and Neonatal Edition 100 (3):F257–F263. doi: 10.1136/archdischild-2014-306213.
  • DiPalma, J., C. L. Kirk, M. Hamosh, A. R. Colon, S. B. Benjamin, and P. Hamosh. 1991. Lipase and pepsin activities in the gastric mucosa of infants, children and adults. Gastroenterology 101 (1):116–21. doi: 10.1055/s-2007-1010677.
  • Drago-Serrano, M. E., M. Garza-Amaya, J. S. Luna, and R. Campos-Rodríguez. 2012. Lactoferrin-lipopolysaccharide (LPS) binding as key to antibacterial and antiendotoxic effects. International Immunopharmacology 12 (1):1–9. doi: 10.1016/j.intimp.2011.11.002.
  • Van Den Driessche, M., K. Peeters, P. Marien, Y. Ghoos, H. Devlieger, and G. Veereman-Wauters. 1999. Gastric emptying in formula-fed and breast-fed infants measured with the C-13-octanoic acid breath test. Journal of Pediatric Gastroenterology and Nutrition 29 (1):46–51. doi: 10.1097/00005176-199907000-00013.
  • EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) 2012. Scientific opinion on bovine lactoferrin. EFSA Journal 10:2811. doi: 10.2903/j.efsa.2012.2811.
  • El-Hawy, M. A., S. Al-Salam, and W. A. Bahbah. 2021. Comparing oral iron bisglycinate chelate, lactoferrin, lactoferrin with iron and iron polymaltose complex in the treatment of children with iron deficiency anemia. Clinical Nutrition ESPEN 46:367–71. doi: 10.1016/j.clnesp.2021.08.040.
  • Elzoghby, A. O., M. A. Abdelmoneem, I. A. Hassanin, M. M. Abd Elwakil, M. A. Elnaggar, S. Mokhtar, J. Y. Fang, and K. A. Elkhodairy. 2020. Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand. Biomaterials 263:120355. doi: 10.1016/j.biomaterials.2020.120355.
  • Fan, F., M. Liu, P. Shi, S. Xu, W. Lu, and M. Du. 2019. Effects of thermal treatment on the physicochemical properties and osteogenic activity of lactoferrin. Journal of Food Processing and Preservation 43 (9):e14068. doi: 10.1111/jfpp.14068.
  • Fernandes, K. E., and D. A. Carter. 2017. The antifungal activity of lactoferrin and its derived peptides: Mechanisms of action and synergy with drugs against fungal pathogens. Frontiers in Microbiology 8:2. doi: 10.3389/fmicb.2017.00002.
  • Fernández‐Menéndez, S., M. Fernández‐Sánchez, R. R. A. Peixoto, B. Fernandez-Colomer, and A. Sanz-Medel. 2018. In vivo study of the effect of lactoferrin on iron metabolism and bioavailability from different iron chemical species for formula milk fortification. Electrophoresis 39 (13):1702–13. doi: 10.1002/elps.201700231.
  • Fillebeen, C., L. Descamps, M.-P. Dehouck, L. Fenart, M. Benaı̈ssa, G. Spik, R. Cecchelli, and A. Pierce. 1999. Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. Journal of Biological Chemistry 274 (11):7011–7. doi: 10.1046/j.1471-4159.1999.0730260.x.
  • Fischer, R., H. Debbabi, A. Blais, M. Dubarry, M. Rautureau, P. N. Boyaka, and D. Tome. 2007. Uptake of ingested bovine lactoferrin and its accumulation in adult mouse tissues. International Immunopharmacology 7 (10):1387–93. doi: 10.1016/j.intimp.2007.05.019.
  • Fleischmann, C., F. Reichert, A. Cassini, R. Horner, T. Harder, R. Markwart, M. Tröndle, Y. Savova, N. Kissoon, P. Schlattmann, et al. 2021. Global incidence and mortality of neonatal sepsis: A systematic review and meta-analysis. Archives of Disease in Childhood 106 (8):745–52. doi: 10.1136/archdischild-2020-320217.
  • Furtado, G. F., O. Ménard, X. Yu, J. Ossemond, G. Henry, J. Jardin, V. Briard-Bion, A. Deglaire, M. D. Hubinger, and D. Dupont. 2021. In vitro dynamic digestion of model infant formulae containing lactoferrin and medium chain triacylglycerols. Food Hydrocolloids. 118:106787. doi: 10.1016/j.foodhyd.2021.106787.
  • Gan, J., G. M. Bornhorst, B. M. Henrick, and J. B. German. 2018. Protein digestion of baby foods: Study approaches and implications for infant health. Molecular Nutrition & Food Research 62 (1):1700231. doi: 10.1002/mnfr.201700231.
  • Garas, L. C., C. Feltrin, M. K. Hamilton, J. V. Hagey, J. D. Murray, L. R. Bertolini, M. Bertolini, H. E. Raybould, and E. A. Maga. 2016. Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition. Food & Function 7 (2):665–78. doi: 10.1039/C5FO01217A.
  • Ginet, V., Y. van de Looij, V. Petrenko, A. Toulotte, J. Kiss, P. S. Hüppi, and S. V. Sizonenko. 2016. Lactoferrin during lactation reduces lipopolysaccharide-induced brain injury. BioFactors (Oxford, England) 42 (3):323–36. doi: 10.1002/biof.1278.
  • Gleeson, J. P., K. C. Fein, N. Chaudhary, R. Doerfler, A. N. Newby, and K. A. Whitehead. 2021. The enhanced intestinal permeability of infant mice enables oral protein and macromolecular absorption without delivery technology. International Journal of Pharmaceutics 593:120120. doi: 10.1016/j.ijpharm.2020.120120.
  • Goldman, A. S., C. Garza, R. J. Schanler, and R. M. Goldblum. 1990. Molecular forms of lactoferrin in stool and urine from infants fed human milk. Pediatric Research 27 (3):252–5. doi: 10.1203/00006450-199003000-00009.
  • Goldman, I. L., S. G. Georgieva, Y. G. Gurskiy, A. N. Krasnov, A. V. Deykin, A. N. Popov, T. G. Ermolkevich, A. I. Budzevich, A. D. Chernousov, and E. R. Sadchikova. 2012. Production of human lactoferrin in animal milk. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire 90 (3):513–9. doi: 10.1139/o11-088.
  • Goulding, D. A., K. Vidal, L. Bovetto, J. O'Regan, N. M. O'Brien, and J. A. O'Mahony. 2021. The impact of thermal processing on the simulated infant gastrointestinal digestion, bactericidal and anti-inflammatory activity of bovine lactoferrin–an in vitro study. Food Chemistry 362:130142. doi: 10.1016/j.foodchem.2021.130142.
  • Grand View Research. Lactoferrin Market Size, Share & Trends Analysis Report By Function (Iron Absorption, Intestinal Flora Protection), By Application (Personal Care Products, Infant Formula), By Region (APAC, Europe), And Segment Forecasts, 2021-2028. Assessed November 8, 2021. https://www.grandviewresearch.com/industry-analysis/lactoferrin-market.
  • GRAS Notice (GRN) No.669. 2016. Bovine Milk-derived Lactoferrin in Term Infant Formulas. Assessed June 24, 2022. https://www.fda.gov/media/124472/download.
  • Grey, A., Q. Zhu, M. Watson, K. Callon, and J. Cornish. 2006. Lactoferrin potently inhibits osteoblast apoptosis, via an LRP1-independent pathway. Molecular and Cellular Endocrinology 251 (1-2):96–102. doi: 10.1016/j.mce.2006.03.002.
  • Griffiths, J., P. Jenkins, M. Vargova, U. Bowler, E. Juszczak, A. King, L. Linsell, D. Murray, C. Partlett, M. Patel, et al. 2019. Enteral lactoferrin supplementation for very preterm infants: A randomised placebo-controlled trial. The Lancet 393 (10170):423–33. doi: 10.1016/S0140-6736(18)32221-9.
  • Groves, M. L. 1960. The isolation of a red protein from milk. Journal of the American Chemical Society 82 (13):3345–50. doi: 10.1021/ja01498a029.
  • Grzywacz, K., J. Butcher, J. Li, K. Barrington, I. Mohamed, and A. Stintzi. 2020. Bovine lactoferrin supplementation does not disrupt microbiota development in preterm infants receiving probiotics. Journal of Pediatric Gastroenterology and Nutrition 71 (2):216–22. doi: 10.1097/MPG.0000000000002734.
  • Hao, Y., J. Wang, D. Teng, X. Wang, R. Mao, N. Yang, and X. Ma. 2021. A prospective on multiple biological activities of lactoferrin contributing to piglet welfare. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire 99 (1):66–72. doi: 10.1139/bcb-2020-0078.
  • Harada, E., Y. Itoh, K. Sitizyo, T. Takeuchi, Y. Araki, and H. Kitagawa. 1999. Characteristic transport of lactoferrin from the intestinal lumen into the bile via the blood in piglets. Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology 124 (3):321–7. doi: 10.1016/S1095-6433(99)00122-1.
  • Jenssen, H., and R. E. W. Hancock. 2009. Antimicrobial properties of lactoferrin. Biochimie 91 (1):19–29. doi: 10.1016/j.biochi.2008.05.015.
  • He, J., and P. Furmanski. 1995. Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA. Nature 373 (6516):721–4. doi: 10.1038/373721a0.
  • Hernell, O., and B. Lönnerdal. 2002. Iron status of infants fed low-iron formula: No effect of added bovine lactoferrin or nucleotides. The American Journal of Clinical Nutrition 76 (4):858–64. doi:10.1051/rnd:2002047
  • Hu, P., F. Zhao, J. Wang, and W. Zhu. 2020. Lactoferrin attenuates lipopolysaccharide-stimulated inflammatory responses and barrier impairment through the modulation of NF-κB/MAPK/Nrf2 pathways in IPEC-J2 cells. Food & Function 11 (10):8516–26. doi: 10.1039/d0fo01570a.
  • Hu, P., F. Zhao, J. Wang, and W. Zhu. 2020. Early-life lactoferrin intervention modulates the colonic microbiota, colonic microbial metabolites and intestinal function in suckling piglets. Applied Microbiology and Biotechnology 104 (14):6185–97. doi: 10.1007/s00253-020-10675-z.
  • Inubushi, T., A. Kosai, S. Yanagisawa, C. Chanbora, M. Miyauchi, S. Yamasaki, E. Sugiyama, A. Ishikado, T. Makino, and T. Takata. 2020. Bovine lactoferrin enhances osteogenesis through Smad2/3 and p38 MAPK activation. Journal of Oral Biosciences 62 (2):147–54. doi: 10.1016/j.job.2020.05.001.
  • Ip, S., M. Chung, G. Raman, P. Chew, and N. Magula. 2007. Breastfeeding and maternal and infant health outcomes in developed countries. Evidence Report/Technology Assessment 153:1–186. doi: 10.1542/gr.18-2-15.
  • Isaacs, E. B., B. R. Fischl, B. T. Quinn, W. K. Chong, D. G. Gadian, and A. Lucas. 2010. Impact of breast milk on intelligence quotient, brain size, and white matter development. Pediatric Research 67 (4):357–62. doi: 10.1203/PDR.0b013e3181d026da.
  • Jenssen, H. 2005. Anti herpes simplex virus activity of lactoferrin/lactoferricin–an example of antiviral activity of antimicrobial protein/peptide. Cellular and Molecular Life Sciences: CMLS 62 (24):3002–13. doi: 10.1007/s00018-005-5228-7.
  • Jiang, R., V. Lopez, S. L. Kelleher, and B. Lönnerdal. 2011. Apo- and holo-lactoferrin are both internalized by lactoferrin receptor via clathrin-mediated endocytosis but differentially affect ERK-signaling and cell proliferation in Caco-2 cells. Journal of Cellular Physiology 226 (11):3022–31. doi: 10.1002/jcp.22650.
  • Jiang, R., and B. Lönnerdal. 2012. Apo- and holo-lactoferrin stimulate proliferation of mouse crypt cells but through different cellular signaling pathways. The International Journal of Biochemistry & Cell Biology 44 (1):91–100. doi: 10.1016/j.biocel.2011.10.002.
  • Jiang, R., and B. Lönnerdal. 2014. Transcriptomic profiling of intestinal epithelial cells in response to human, bovine and commercial bovine lactoferrins. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine 27 (5):831–41. doi: 10.1007/s10534-014-9746-3.
  • Jiménez-Barrios, P., C. M. Jaén-Cano, R. Malumbres, F. Cilveti-Vidaurreta, A. Bellanco-Sevilla, B. Miralles, I. Recio, and M. Martínez-Sanza. 2022. Thermal stability of bovine lactoferrin prepared by cation exchange chromatography and its blends with authorized additives for infant formulas. Lwt 154:112744. doi: 10.1016/j.lwt.2021.112744.
  • Johansson, B. 1960. Isolation of an iron containing red protein from human milk. Acta Chemica Scandinavica 14:510–2. doi: 10.3891/acta.chem.scand.14-0510.
  • Johnston, W. H., C. Ashley, M. Yeiser, C. L. Harris, S. I. Stolz, J. L. Wampler, A. Wittke, and T. R. Cooper. 2015. Growth and tolerance of formula with lactoferrin in infants through one year of age: Double-blind, randomized, controlled trial. BMC Pediatrics 15 (1):11. doi: 10.1186/s12887-015-0488-3.
  • Karav, S., J. German, C. Rouquié, A. Le Parc, and D. Barile. 2017. Studying lactoferrin N-Glycosylation. International Journal of Molecular Sciences 18 (4):870. doi: 10.3390/ijms18040870.
  • Kell, D. B., E. L. Heyden, and E. Pretorius. 2020. The biology of lactoferrin, an iron-binding protein that can help defend against viruses and bacteria. Frontiers in Immunology 11:1221. doi: 10.3389/fimmu.2020.01221.
  • King, J. C., G. E. Cummings, N. Guo, L. Trivedi, B. X. Readmond, V. Keane, S. Feigelman, and R. Waard. 2007. A double-blind, placebo-controlled, pilot study of bovine lactoferrin supplementation in bottle-fed infants. Journal of Pediatric Gastroenterology and Nutrition 44 (2):245–51. doi: 10.1097/01.mpg.0000243435.54958.68.
  • Kong, X., M. Yang, J. Guo, and Z. Feng. 2020. Effects of bovine lactoferrin on rat intestinal epithelial cells. Journal of Pediatric Gastroenterology and Nutrition 70 (5):645–51. doi: 10.1097/MPG.0000000000002636.
  • Krolitzki, E., S. P. Schwaminger, M. Pagel, F. Ostertag, J. Hinrichs, and S. Berensmeier. 2022. Current practices with commercial scale bovine lactoferrin production and alternative approaches. International Dairy Journal 126:105263. doi: 10.1016/j.idairyj.2021.105263.
  • Kucova, P., L. Kantor, K. Fiserova, J. Lasak, M. Röderová, and M. Kolar. 2021. Bacterial pathogens and evaluation of a cut-off for defining early and late neonatal infection. Antibiotics 10 (3):278. doi: 10.3390/antibiotics10030278.
  • Kumar, B. S. G., and S. Mattad. 2021. Comprehensive analysis of lactoferrin N-glycans with site-specificity from bovine colostrum using specific proteases and RP-UHPLC-MS/MS. International Dairy Journal 119:104999. doi: 10.1016/j.idairyj.2021.104999.
  • Lambert, L. A., H. Perri, and T. J. Meehan. 2005. Evolution of duplications in the transferrin family of proteins. Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology 140 (1):11–25. doi: 10.1016/j.cbpc.2004.09.012.
  • Lee, H. Y., J. H. Park, S. H. Seok, M. W. Baek, D. J. Kim, B. H. Lee, P. D. Kang, Y. S. Kim, and J. H. Park. 2005. Potential antimicrobial effects of human lactoferrin against oral infection with Listeria monocytogenes in mice. Journal of Medical Microbiology 54 (Pt 11):1049–54. doi: 10.1099/jmm.0.45918-0.
  • Legrand, D. 2016. Overview of lactoferrin as a natural immune modulator. The Journal of Pediatrics 173:S10–S15. doi: 10.1016/j.jpeds.2016.02.071.
  • Li, S., H. Zhou, G. Huang, and N. Liu. 2009. Inhibition of HBV infection by bovine lactoferrin and iron-, zinc-saturated lactoferrin. Medical Microbiology and Immunology 198 (1):19–25. doi: 10.1007/s00430-008-0100-7.
  • Li, W., J. Wang, Y. Lin, Y. Li, F. Ren, and H. Guo. 2021a. How far is it from infant formula to human milk? A look at the human milk oligosaccharides. Trends in Food Science & Technology 118:374–87. doi: 10.1016/j.tifs.2021.09.021.
  • Li, F., S. S. Wu, C. L. Berseth, C. L. Harris, J. D. Richards, J. L. Wampler, W. Zhuang, G. Cleghorn, C. D. Rudolph, B. Liu, et al. 2019. Improved neurodevelopmental outcomes associated with bovine milk fat globule membrane and lactoferrin in infant formula: A randomized, controlled trial. The Journal of Pediatrics 215:24–31.e8. doi: 10.1016/j.jpeds.2019.08.030.
  • Li, H.-Y., H.-G. Yang, P. Li, Y.-Z. Wang, G.-X. Huang, L. Xing, J.-Q. Wang, and N. Zheng. 2019. Effect of heat treatment on the antitumor activity of lactoferrin in human colon tumor (HT29) model. Journal of Agricultural and Food Chemistry 67 (1):140–7. doi: 10.1021/acs.jafc.8b05131.
  • Li, Q., W. Hu, J. Zhao, J. Wang, Y. Dai, Y. Zhao, Q. Meng, and N. Li. 2014. Supplementation transgenic cow’s milk containing recombinant human lactoferrin enhances systematic and intestinal immune responses in piglets. Molecular Biology Reports 41 (4):2119–28. doi: 10.1007/s11033-014-3061-5.
  • Li, Q., J. Zhao, W. Hu, J. Wang, T. Yu, Y. Dai, and N. Li. 2018. Effects of recombinant human lactoferrin on osteoblast growth and bone status in piglets. Animal Biotechnology 29 (2):90–9. doi: 10.1080/10495398.2017.1313269.
  • Li, Y., J. Huang, J. Wang, M. Ma, Y. Lu, R. Wang, and H. Guo. 2021b. Lactoferrin is a potential activator of the vitamin D receptor in its regulation of osteogenic activities in C57BL/6J mice and MC3T3-E1 cells. The Journal of Nutrition 151 (8):2105–13. doi: 10.1093/jn/nxab105.
  • Liao, Y., R. Jiang, and B. Lönnerdal. 2012. Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire 90 (3):476–84. doi: 10.1139/O11-075.
  • Liu, K. Y., S. S. Comstock, J. M. Shunk, M. H. Monaco, and S. M. Donovan. 2013. Natural killer cell populations and cytotoxic activity in pigs fed mother’s milk, formula, or formula supplemented with bovine lactoferrin. Pediatric Research 74 (4):402–7. doi: 10.1038/pr.2013.125.
  • Liu, M., M. Du, Y. Kong, W. Xu, W. Song, and L. Zhang. 2013. Influence of heat treatment on the osteoblast-promoting activity of bovine lactoferrin. Food Science 34:301–4. doi: 10.7506/spkx1002-6630-201309061.
  • Liu, Y., M. Perego, Q. Xiao, Y. He, S. Fu, J. He, W. Liu, X. Li, Y. Tang, X. Li, et al. 2019. Lactoferrin-induced myeloid-derived suppressor cell therapy attenuates pathologic inflammatory conditions in newborn mice. Journal of Clinical Investigation 129 (10):4261–75. doi: 10.1172/JCI128164.
  • Liu, Y., W. Zhang, B. Han, L. Zhang, and P. Zhou. 2020. Changes in bioactive milk serum proteins during milk powder processing. Food Chemistry 314:126177. doi: 10.1016/j.foodchem.2020.126177.
  • Lönnerdal, B. 2010. Alternative pathways for absorption of iron from foods. Pure and Applied Chemistry 82 (2):429–36. doi: 10.1351/PAC-CON-09-06-04.
  • Lönnerdal, B. 2009. Nutritional roles of lactoferrin. Current Opinion in Clinical Nutrition and Metabolic Care 12 (3):293–7. doi: 10.1097/mco.0b013e328328d13e.
  • Lu, J., J. D. Francis, M. A. Guevara, R. E. Moore, S. A. Chambers, R. S. Doster, A. J. Eastman, L. M. Rogers, K. N. Noble, S. D. Manning, et al. 2021. Antibacterial and anti-biofilm activity of the human breast milk glycoprotein lactoferrin against group B streptococcus. Chembiochem: A European Journal of Chemical Biology 22 (12):2124–33. doi: 10.1002/cbic.202100016.
  • Ma, Y., Y. Hou, K. Xie, L. Zhang, and P. Zhou. 2021. Digestive differences in immunoglobulin G and lactoferrin among human, bovine, and caprine milk following in vitro digestion. International Dairy Journal 120:105081. doi: 10.1016/j.idairyj.2021.105081.
  • Manzoni, P. 2016. Clinical benefits of lactoferrin for infants and children. The Journal of Pediatrics 173:S43–S52. doi: 10.1016/j.jpeds.2016.02.075.
  • Manzoni, P., E. Jacqz-Aigrain, S. Rizzollo, C. Franco, M. Stronati, M. Mostert, and D. Farina. 2011. Antifungal prophylaxis in neonates. Early Human Development 87:S59–S60. doi: 10.1016/j.earlhumdev.2011.01.013.
  • Manzoni, P., M. Rinaldi, S. Cattani, L. Pugni, M. G. Romeo, H. Messner, I. Stolfi, L. Decembrino, N. Laforgia, F. Vagnarelli, et al. 2009. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: A randomized trial. JAMA-Journal of the American Medical Association 302 (13):1421–8. doi: 10.1001/jama.2009.1403.
  • Manzoni, P., I. Stolfi, H. Messner, S. Cattani, N. Laforgia, M. G. Romeo, L. Bollani, M. Rinaldi, E. Gallo, M. Quercia, et al. 2012. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: A randomized controlled trial. Pediatrics 129 (1):116–23. doi: 10.1542/peds.2011-0279.
  • Manzoni, P., A. Dall’Agnola, D. Tomé, D. A. Kaufman, E. Tavella, M. Pieretto, A. Messina, D. De Luca, M. Bellaiche, A. Mosca, et al. 2018. Role of lactoferrin in neonates and infants: An update. American Journal of Perinatology 35 (6):561–5. doi: 10.1055/s-0038-1639359.
  • Manzoni, P., M. Meyer, I. Stolfi, M. Rinaldi, S. Cattani, L. Pugni, M. G. Romeo, H. Messner, L. Decembrino, N. Laforgia, et al. 2014. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: A randomized clinical trial. Early Human Development 90:S60–S65. doi: 10.1055/s-0032-1321494.
  • Masum, A. K. M., J. Chandrapala, T. Huppertz, B. Adhikari, and B. Zisu. 2021. Production and characterization of infant milk formula powders: A review. Drying Technology 39 (11):1492–512. doi: 10.1080/07373937.2020.1767645.
  • Matsuzaki, T., M. Nakamura, T. Nogita, and A. Sato. 2019. Cellular uptake and release of intact lactoferrin and its derivatives in an intestinal enterocyte model of Caco-2 cells. Biological & Pharmaceutical Bulletin 42 (6):989–95. doi: 10.1248/bpb.b19-00011.
  • Mayeur, S., S. Spahis, Y. Pouliot, and E. Levy. 2016. Lactoferrin, a pleiotropic protein in health and disease. Antioxidants & Redox Signaling 24 (14):813–36. doi: 10.1089/ars.2015.6458.
  • Mccarthy, N. A., A. L. Kelly, J. A. O'Mahony, and M. A. Fenelon. 2014. Sensitivity of emulsions stabilised by bovine β-casein and lactoferrin to heat and CaCl2. Food Hydrocolloids. 35:420–8. doi: 10.1016/j.foodhyd.2013.06.021.
  • Ménard, O., C. Bourlieu, S. C. De Oliveira, N. Dellarosa, L. Laghi, F. Carrière, F. Capozzi, D. Dupont, and A. Deglaire. 2018. A first step towards a consensus static in vitro model for simulating full-term infant digestion. Food Chemistry 240:338–45. doi: 10.1016/j.foodchem.2017.07.145.
  • Moore, M. R., S. J. Schrag, and A. Schuchat. 2003. Effects of intrapartum antimicrobial prophylaxis for prevention of group-B-streptococcal disease on the incidence and ecology of early-onset neonatal sepsis. The Lancet. Infectious Diseases 3 (4):201–13. doi: 10.1016/S1473-3099(03)00577-2.
  • Moore, S. A., B. F. Anderson, C. R. Groom, M. Haridas, and E. N. Baker. 1997. Three-dimensional structure of diferric bovine lactoferrin at 2.8 Å resolution. Journal of Molecular Biology 274 (2):222–36. doi: 10.1006/jmbi.1997.1386.
  • Morel, J., S. N. M. Zain, and R. Archer. 2022. Comparison of drying techniques for bovine lactoferrin: Iron binding and antimicrobial properties of dried lactoferrin. International Dairy Journal 124:105142. doi: 10.1016/j.idairyj.2021.105142.
  • Navarro, F., S. Harouna, M. Calvo, M. D. Pérez, and L. Sánchez. 2015. Kinetic and thermodynamic parameters for thermal denaturation of ovine milk lactoferrin determined by its loss of immunoreactivity. Journal of Dairy Science 98 (7):4328–37. doi: 10.3168/jds.2015-9403.
  • Nguyen, D. N., P. Jiang, A. Stensballe, E. Bendixen, P. T. Sangild, and D. E. W. Chatterton. 2016. Bovine lactoferrin regulates cell survival, apoptosis and inflammation in intestinal epithelial cells and preterm pig intestine. Journal of Proteomics 139:95–102. doi: 10.1016/j.jprot.2016.03.020.
  • Nicolas, P., M. L. Ferreira, and V. Lassalle. 2019. A review of magnetic separation of whey proteins and potential application to whey proteins recovery, isolation and utilization. Journal of Food Engineering 246:7–15. doi: 10.1016/j.jfoodeng.2018.10.021.
  • Ochoa, T. J., J. Zegarra, L. Cam, R. Llanos, A. Pezo, K. Cruz, A. Zea-Vera, C. Cárcamo, M. Campos, and S. Bellomo, NEOLACTO Research Group 2015. Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates <2500 grams. The Pediatric Infectious Disease Journal 34 (6):571–6. doi: 10.1097/INF.0000000000000593.
  • Ochoa, T. J., E. Chea-Woo, N. Baiocchi, I. Pecho, M. Campos, A. Prada, G. Valdiviezo, A. Lluque, D. Lai, and T. G. Cleary. 2013. Randomized double-blind controlled trial of bovine lactoferrin for prevention of diarrhea in children. The Journal of Pediatrics 162 (2):349–56. doi: 10.1016/j.jpeds.2012.07.043.
  • Ochoa, T. J., J. Zegarra, S. Bellomo, C. P. Carcamo, L. Cam, A. Castañeda, A. Villavicencio, J. Gonzales, M. S. Rueda, C. G. Turin, NEOLACTO Research Group, et al. 2020. Randomized controlled trial of bovine lactoferrin for prevention of sepsis and neurodevelopment impairment in infants weighing less than 2000 grams. The Journal of Pediatrics 219:118–25.e5. doi: 10.1016/j.jpeds.2019.12.038.
  • Pammi, M., and G. Suresh. 2020. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. The Cochrane Database of Systematic Reviews 3 (3):CD007137. doi: 10.1002/14651858.CD007137.pub6.
  • Pérez-Cano, F. J., S. Marín-Gallén, M. Castell, M. Rodríguez-Palmero, M. Rivero, C. Castellote, and A. Franch. 2008. Supplementing suckling rats with whey protein concentrate modulates the immune response and ameliorates rat rotavirus-induced diarrhea. The Journal of Nutrition 138 (12):2392–8. doi: 10.3945/jn.108.093856.
  • Prenner, M. L., C. Prgomet, H. Sauerwein, M. W. Pfaffl, J. Broz, and F. J. Schwarz. 2007. Effects of lactoferrin feeding on growth, feed intake and health of calves. Archives of Animal Nutrition 61 (1):20–30. doi: 10.1080/17450390600973675.
  • Rascón-Cruz, Q., E. A. Espinoza-Sánchez, T. S. Siqueiros-Cendón, S. I. Nakamura-Bencomo, S. Arévalo-Gallegos, and B. F. Iglesias-Figueroa. 2021. Lactoferrin: A glycoprotein involved in immunomodulation, anticancer, and antimicrobial processes. Molecules 26 (1):205. doi: 10.3390/molecules26010205.
  • Rastogi, N., A. Singh, P. K. Singh, T. K. Tyagi, S. Pandey, K. Shin, P. Kaur, S. Sharma, and T. P. Singh. 2016. Structure of iron saturated C lobe of bovine lactoferrin at pH 6.8 indicates a weakening of iron coordination. Proteins 84 (5):591–9. doi: 10.1002/prot.25004.
  • Reznikov, E. A., S. S. Comstock, J. L. Hoeflinger, M. Wang, M. J. Miller, and S. M. Donovan. 2018. Dietary bovine lactoferrin reduces Staphylococcus aureus in the tissues and modulates the immune response in piglets systemically infected with S. aureus. Current Developments in Nutrition 2 (4):nzy001. doi: 10.1093/cdn/nzy001.
  • Reznikov, E. A., S. S. Comstock, C. Yi, N. Contractor, and S. M. Donovan. 2014. Dietary bovine lactoferrin increases intestinal cell proliferation in neonatal piglets. The Journal of Nutrition 144 (9):1401–8. doi: 10.3945/jn.114.196568.
  • Rybarczyk, J., E. Kieckens, D. Vanrompay, and E. Cox. 2017. In vitro and in vivo studies on the antimicrobial effect of lactoferrin against Escherichia coli O157:H7. Veterinary Microbiology 202:23–8. doi: 10.1016/j.vetmic.2016.05.010.
  • Salar, S., S. Jafarian, A. Mortazavi, and L. R. Nasiraie. 2021. Effect of hurdle technology of gentle pasteurisation and drying process on bioactive proteins, antioxidant activity and microbial quality of cow and buffalo colostrum. International Dairy Journal 121:105138. doi: 10.1016/j.idairyj.2021.105138.
  • Samson, R. R., C. Mirtle, and D. B. L. Mcclelland. 1980. The effect of digestive enzymes on the binding and bacteriostatic properties of lactoferrin and vitamin B12 binder in human milk. Acta Paediatrica 69 (4):517–23. doi: 10.1111/j.1651-2227.1980.tb07124.x.
  • Sánchez, C., L. Franco, P. Regal, A. Lamas, A. Cepeda, and C. Fente. 2021. Breast milk: A source of functional compounds with potential application in nutrition and therapy. Nutrients 13 (3):1026. doi: 10.3390/nu13031026.
  • Sawale, M., F. Ozadali, C. J. Valentine, P. Benyathiar, R. Drolia, and D. K. Mishra. 2022. Impact of bovine lactoferrin fortification on pathogenic organisms to attenuate the risk of infection for infants. Food Control. 139:109078. doi: 10.1016/j.foodcont.2022.109078.
  • Schanler, R. J., R. M. Goldblum, C. Garza, and A. S. Goldman. 1986. Enhanced fecal excretion of selected immune factors in very low birth weight infants fed fortified human milk. Pediatric Research 20 (8):711–5. doi: 10.1203/00006450-198608000-00002.
  • Shahidi, F., S. Roshanak, A. Javadmanesh, F. T. Yazdi, Z. Pirkhezranian, and M. Azghandi. 2020. Evaluation of antimicrobial properties of bovine lactoferrin against foodborne pathogenic microorganisms in planktonic and biofilm forms (in vitro). Journal of Consumer Protection and Food Safety 15 (3):277–83. doi: 10.1007/s00003-020-01280-3.
  • Shan, T., Y. Wang, Y. Wang, J. Liu, and Z. Xu. 2007. Effect of dietary lactoferrin on the immune functions and serum iron level of weanling piglets. Journal of Animal Science 85 (9):2140–6. doi: 10.2527/jas.2006-754.
  • Shani-Levi, C., S. Levi-Tal, and U. Lesmes. 2013. Comparative performance of milk proteins and their emulsions under dynamic in vitro adult and infant gastric digestion. Food Hydrocolloids. 32 (2):349–57. doi: 10.1016/j.foodhyd.2013.01.017.
  • Sherman, M. P., C. J. Pritzl, C. Xia, M. M. Miller, H. Zaghouani, and B. Hahm. 2015. Lactoferrin acts as an adjuvant during influenza vaccination of neonatal mice. Biochemical and Biophysical Research Communications 467 (4):766–70. doi: 10.1016/j.bbrc.2015.10.067.
  • Shumake, J., D. W. Barrett, M. A. Lane, and A. J. Wittke. 2014. Behavioral effects of bovine lactoferrin administration during postnatal development of rats. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine 27 (5):1039–55. doi: 10.1007/s10534-014-9735-6.
  • Sienkiewicz, M., A. Jaśkiewicz, A. Tarasiuk, and J. Fichna. 2022. Lactoferrin: An overview of its main functions, immunomodulatory and antimicrobial role, and clinical significance. Critical Reviews in Food Science and Nutrition. 62 (22):6016–33. doi: 10.1080/10408398.2021.1895063.
  • Spik, G., B. Brunet, C. Mazurier‐Dehaine, G. Fontaine, and J. Montreuil. 1982. Characterization and properties of the human and bovine lactotransferrins extracted from the faeces of newborn infants. Acta Paediatrica Scandinavica 71 (6):979–85. doi: 10.1111/j.1651-2227.1982.tb09560.x.
  • Srensen, M., and S. P. L. Srensen. 1939. The proteins in whey. Comptes Rendus Des Travaux Du Laboratoire Carlsberg 23:55–99.
  • Sucheta, T. 2018. Lactoferrin: A critical player in neonatal host defense. Nutrients 10:1228. doi: 10.3390/nu10091228xx.
  • Talukder, M., T. Takeuchi, and E. Harada. 2002. Transport of colostral macromolecules into the cerebrospinal fluid via plasma in newborn calves. Journal of Dairy Science 85 (3):514–24. doi: 10.3168/jds.S0022-0302(02)74103-9.
  • Tokle, T., and D. J. Mcclements. 2011. Physicochemical properties of lactoferrin stabilized oil-in-water emulsions: Effects of pH, salt and heating. Food Hydrocolloids. 25 (5):976–82. doi: 10.1016/j.foodhyd.2010.09.012.
  • Troost, F. J., J. Steijns, W. H. M. Saris, and R. J. M. Brummer. 2001. Gastric digestion of bovine lactoferrin in vivo in adults. The Journal of Nutrition 131 (8):2101–4. doi: 10.1093/jn/131.8.2101.
  • Valk-Weeber, R. L., T. E. de-Ruiter, L. Dijkhuizen, and S. S. van Leeuwen. 2020. Dynamic temporal variations in bovine lactoferrin glycan structures. Journal of Agricultural and Food Chemistry 68 (2):549–60. doi: 10.1021/acs.jafc.9b06762.
  • van de Looij, Y., V. Ginet, A. Chatagner, A. Toulotte, E. Somm, P. S. Hüppi, and S. V. Sizonenko. 2014. Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain. Annals of Clinical and Translational Neurology 1 (12):955–67. doi: 10.1002/acn3.138.
  • van Veen, H. A., M. E. J. Geerts, P. H. C. van Berkel, and J. H. Nuijens. 2004. The role of N-linked glycosylation in the protection of human and bovine lactoferrin against tryptic proteolysis. European Journal of Biochemistry 271 (4):678–84. doi: 10.1111/j.1432-1033.2003.03965.x.
  • Velliyagounder, K., W. Alsaedi, W. Alabdulmohsen, K. Markowitz, and D. H. Fine. 2015. Oral lactoferrin protects against experimental candidiasis in mice. Journal of Applied Microbiology 118 (1):212–21. doi: 10.1111/jam.12666.
  • Velliyagounder, K., S. D. Rozario, and D. H. Fine. 2019. The effects of human lactoferrin in experimentally induced systemic candidiasis. Journal of Medical Microbiology 68 (12):1802–12. doi: 10.1099/jmm.0.001098.
  • Venkatesh, M., and S. Abrams. 2009. Can lactoferrin prevent neonatal sepsis and necrotizing enterocolitis. Expert Review of anti-Infective Therapy 7 (5):515–25. doi: 10.1586/eri.09.25.
  • Vogel, H. J. 2012. Lactoferrin, a bird’s eye view. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire 90 (3):233–44. doi: 10.1139/O2012-016.
  • Voswinkel, L., T. Vogel, and U. Kulozik. 2016. Impact of the iron saturation of bovine lactoferrin on adsorption to a strong cation exchanger membrane. International Dairy Journal 56:134–40. doi: 10.1016/j.idairyj.2016.01.008.
  • Wakabayashi, H., T. Hiratani, K. Uchida, and H. Yamaguchi. 1996. Antifungal spectrum and fungicidal mechanism of an N-terminal peptide of bovine lactoferrin. Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy 1 (3):185–9. doi: 10.1007/BF02350646.
  • Wakabayashi, H., M. Kurokawa, K. Shin, S. Teraguchi, Y. Tamura, and K. Shiraki. 2004. Oral lactoferrin prevents body weight loss and increases cytokine responses during herpes simplex virus type 1 infection of mice. Bioscience, Biotechnology, and Biochemistry 68 (3):537–44. doi: 10.1271/bbb.68.537.
  • Wally, J., and S. K. Buchanan. 2007. A structural comparison of human serum transferrin and human lactoferrin. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine 20 (3-4):249–62. doi: 10.1007/s10534-006-9062-7.
  • Wang, B., Y. P. Timilsena, E. Blanch, and B. Adhikari. 2019. Lactoferrin: Structure, function, denaturation and digestion. Critical Reviews in Food Science and Nutrition 59 (4):580–96. doi: 10.1080/10408398.2017.1381583.
  • Wang, B. 2016. Molecular determinants of milk lactoferrin as a bioactive compound in early neurodevelopment and cognition. The Journal of Pediatrics 173:S29–S36. doi: 10.1016/j.jpeds.2016.02.073.
  • Wang, B. 2012. Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition. Advances in Nutrition (Bethesda, Md.) 3 (3):465S–72S. doi: 10.3945/an.112.001875.
  • Wang, B., Y. P. Timilsena, E. Blanch, and B. Adhikari. 2017. Characteristics of bovine lactoferrin powders produced through spray and freeze drying processes. International Journal of Biological Macromolecules 95:985–94. doi: 10.1016/j.ijbiomac.2016.10.087.
  • Wang, W., Z. Cheng, X. Wang, Q. An, K. Huang, Y. Dai, Q. Meng, and Y. Zhang. 2021. Lactoferrin, a critical player in neonate intestinal development: RhLF may be a good choice in formula. Journal of Agricultural and Food Chemistry 69 (31):8726–36. doi: 10.1021/acs.jafc.1c03129.
  • Wang, Y. Z., T. Z. Shan, Z. R. Xu, J. Feng, and Z. Q. Wang. 2007. Effects of the lactoferrin (LF) on the growth performance, intestinal microflora and morphology of weanling pigs. Animal Feed Science and Technology 135 (3-4):263–72. doi: 10.1016/j.anifeedsci.2006.07.013.
  • Wei, Y-s., K. Feng, S-f Li, T-g Hu, R. J. Linhardt, M-h Zong, and H. Wu. 2022. Oral fate and stabilization technologies of lactoferrin: A systematic review. Critical Reviews in Food Science and Nutrition 62 (23):6341–58. doi: 10.1080/10408398.2021.1900774.
  • Wisgrill, L., I. Wessely, A. Spittler, E. Förster-Waldl, A. Berger, and K. Sadeghi. 2018. Human lactoferrin attenuates the proinflammatory response of neonatal monocyte-derived macrophages. Clinical and Experimental Immunology 192 (3):315–24. doi: 10.1111/cei.13108.
  • Xiong, L., S. Boeren, J. Vervoort, and K. Hettinga. 2021. Effect of milk serum proteins on aggregation, bacteriostatic activity and digestion of lactoferrin after heat treatment. Food Chemistry 337:127973. doi: 10.1016/j.foodchem.2020.127973.
  • Xu, Y., T. Zhao, H. Ren, Y. Xie, J. An, J. Shang, D. Tabys, and N. Liu. 2020. Urinary metabolic profiling via LC-MS/MS reveals impact of bovine lactoferrin on bone formation in growing SD rats. Nutrients 12 (4):1116. doi: 10.3390/nu12041116.
  • Yang, Z., R. Jiang, Q. Chen, J. Wang, Y. Duan, X. Pang, S. Jiang, Y. Bi, H. Zhang, B. Lönnerdal, et al. 2018. Concentration of lactoferrin in human milk and its variation during lactation in different Chinese populations. Nutrients 10 (9):1235. doi: 10.3390/nu10091235.
  • Yang, C., X. Zhu, N. Liu, Y. Chen, H. Gan, F. A. Troy, and B. Wang. 2014. Lactoferrin up-regulates intestinal gene expression of brain-derived neurotrophic factors BDNF, UCHL1 and alkaline phosphatase activity to alleviate early weaning diarrhea in postnatal piglets. The Journal of Nutritional Biochemistry 25 (8):834–42. doi: 10.1016/j.jnutbio.2014.03.015.
  • Yang, H.-G., H.-Y. Li, P. Li, X.-Y. Bao, G.-X. Huang, L. Xing, N. Zheng, and J.-Q. Wang. 2020. Modulation activity of heat-treated and untreated lactoferrin on the TLR-4 pathway in anoxia cell model and cerebral ischemia reperfusion mouse model. Journal of Dairy Science 103 (2):1151–63. doi: 10.3168/jds.2019-17002.
  • Yemets, A. I., I. V. Tanasienko, Y. A. Krasylenko, and Y. B. Blume. 2014. Plant-based biopharming of recombinant human lactoferrin. Cell Biology International 38 (9):989–1002. doi: 10.1002/cbin.10304.
  • Yu, T., C. Guo, J. Wang, P. Hao, S. Sui, X. Chen, R. Zhang, P. Wang, G. Yu, L. Zhang, et al. 2011. Comprehensive characterization of the site-specific N-glycosylation of wild-type and recombinant human lactoferrin expressed in the milk of transgenic cloned cattle. Glycobiology 21 (2):206–24. doi: 10.1093/glycob/cwq151.
  • Zhang, J. L., X. Han, Y. J. Shan, L. W. Zhang, M. Du, M. Liu, H. X. Yi, and Y. Ma. 2018. Effect of bovine lactoferrin and human lactoferrin on the proliferative activity of the osteoblast cell line MC3T3-E1 in vitro. Journal of Dairy Science 101 (3):1827–33. doi: 10.3168/jds.2017-13161.
  • Zhao, T., D. Zuo, Y. Xie, Y. Yan, J. Shang, and N. Liu. 2020. Effect of lactoferrin on bone health in juvenile rats. Science and Technology of Food Industry 41:302–9. doi: 10.13386/j.issn1002-0306.2020.15.047.
  • Zlatina, K., and S. P. Galuska. 2021. The N-glycans of lactoferrin: More than just a sweet decoration. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire 99 (1):117–27. doi: 10.1139/bcb-2020-0106.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.