Lactoferrin is a non-heme iron-binding glycoprotein, and accounts for 15 to 20% of the total protein in breast milk[1]. It is the second most abundant whey protein in human milk, comprising approximately 25% of whey proteins[2] (Rai et al., 2014). Mean lactoferrin levels in mature human milk were reported within a range of 0.44 – 4.4 g/L[2], whereas lower levels have been detected in mature bovine milk at a range of 0.03 – 0.1 g/L[3].

Lactoferrin has been shown to be involved in several physiological functions including the modulation of immune responses; the protection against microbial infection; antiinflammatory effects; antioxidant properties through iron binding; and the regulation of iron absorption in the bowel[4].

Lactoferrin (either alone or in combination with other ingredients) has been clinically shown to enhance resistance to pathogens in preterm very low birth weight neonates[5], healthy infants[6] and children[7].

Lactoferrin has a multimodal mechanism of supporting the gut immune system. Extensive in vitro and animal studies have demonstrated the particular functions of lactoferrin in supporting gut health.

Lactoferrin is found in especially high levels in colostrum, the very early milk a mother produces to provide important immune protection for newborns during their first weeks.

Aspects of lactoferrin related to gastrointestinal health
Animal and cell culture data have shown a beneficial role of lactoferrin in supporting a healthy gastrointestinal system, including:

  • Decreased bacterial translocation[8]
  • Enhanced proliferation and differentiation of enterocytes[9]  Improved intestinal morphology by increasing villus height and decreasing crypt depth[10]  Decreased intestinal permeability[11]
  • Upregulated mucosal defense system and neurotrophic signaling pathway in the gut[12]
  • Promoted the growth of the beneficial lactobacilli and bifidobacteria[13] Immunomodulating properties particularly in the gut

Clinically, lactoferrin (either alone or in combination with other ingredients) was found to exert protection against gastrointestinal infections, and to reduce the incidence of diarrhea in multiple clinical trials.

In young children and children:

  • Lower frequency and duration of vomiting and diarrhea[14]
  • Lower colonization rates with Giardia species[15], and reduced risk of Norovirus-induced gastroenteritis[16]
  • Shorter duration of diarrheal episodes; and reduced longitudinal prevalence of diarrhea, proportion of episodes with moderate/severe dehydration, and liquid stools load/child/year[17]

In preterm very low birth weight neonates:

  • Reduced incidence of necrotizing enterocolitis and associated mortality[18]


[1] Lonnerdal, B. 2014. Infant formula and infant nutrition: bioactive proteins of human milk and implications for composition of infant formulas. Am J Clin Nutr 99(3):712S-717S.
[2] Rai, D., A. S. Adelman, W. Zhuang, G. P. Rai, J. Boettcher, and B. Lonnerdal. 2014.Longitudinal changes in lactoferrin concentrations in human milk: a global systematic review. Crit Rev Food Sci Nutr 54(12):1539-1547.
[3] Lönnerdal, B., R. Jiang, and X. Du. 2011. Bovine lactoferrin can be taken up by the human intestinal lactoferrin receptor and exert bioactivities. J Pediatr Gastroenterol Nutr 53(6):606-614.
[4] Garcia-Montoya, I. A., T. S. Cendon, S. Arevalo-Gallegos, and Q. Rascon-Cruz. 2012. Lactoferrin a multiple bioactive protein: an overview. Biochim Biophys Acta 1820(3):226-236.
[5] Manzoni, P., M. Rinaldi, S. Cattani, L. Pugni, M. G. Romeo, H. Messner, I. Stolfi, L. Decembrino, N. Laforgia, F. Vagnarelli, L. Memo, L. Bordignon, O. S. Saia, M. Maule, E. Gallo, M. Mostert, C. Magnani, M. Quercia, L. Bollani, R. Pedicino, L. Renzullo, P. Betta, F. Mosca, F. Ferrari, R. Magaldi, M. Stronati, D. Farina, and I. S. o. N. Italian Task Force for the Study and Prevention of Neonatal Fungal Infections. 2009. Bovine lactoferrin supplementation for prevention of lateonset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 302(13):1421-1428.
[6] King, J. C., Jr., G. E. Cummings, N. Guo, L. Trivedi, B. X. Readmond, V. Keane, S. Feigelman, and R. de Waard. 2007. A double-blind, placebo-controlled, pilot study of bovine lactoferrin supplementation in bottle-fed infants. J Pediatr Gastroenterol Nutr 44(2):245-251.
[7] Zuccotti, G. V., D. Trabattoni, M. Morelli, S. Borgonovo, L. Schneider, and M. Clerici. 2009.Immune modulation by lactoferrin and curcumin in children with recurrent respiratory infections. J Biol Regul Homeost Agents 23(2):119-123.
[8] Teraguchi, S., K. Shin, T. Ogata, M. Kingaku, A. Kaino, H. Miyauchi, Y. Fukuwatari, and S.Shimamura. 1995. Orally administered bovine lactoferrin inhibits bacterial translocation in mice fed bovine milk. Appl Environ Microbiol 61(11):4131-4134.
[9] Hagiwara, T., I. Shinoda, Y. Fukuwatari, and S. Shimamura. 1995. Effects of lactoferrin and its peptides on proliferation of rat intestinal epithelial cell line, IEC-18, in the presence of epidermal growth factor. Biosci Biotechnol Biochem 59(10):1875-1881.
[10] Wang, Y., T. Shan, Z. Xu, J. Liu, and J. Feng. 2006a. Effect of lactoferrin on the growth performance, intestinal morphology, and expression of PR-39 and protegrin-1 genes in weaned piglets. J Anim Sci 84(10):2636-2641.
[11] Hirotani, Y., K. Ikeda, R. Kato, M. Myotoku, T. Umeda, Y. Ijiri, and K. Tanaka. 2008. Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells. Yakugaku Zasshi 128(9):1363-1368.
[12] Yang, C., X. Zhu, N. Liu, Y. Chen, H. Gan, F. A. Troy, 2nd, and B. Wang. 2014. Lactoferrin upregulates intestinal gene expression of brain-derived neurotrophic factors BDNF, UCHL1 and alkaline phosphatase activity to alleviate early weaning diarrhea in postnatal piglets. J Nutr Biochem 25(8):834-842.
[13] Wang, Y. Z., T. Z. Shan, Z. R. Xu, J. Liu, and J. Feng. 2006b. Effects of the lactoferrin (LF) on the growth performance, intestinal microflora and morphology of weanling pigs. Anim. Feed. Sci. Technol. 135:263-272.
[14] Egashira, M., T. Takayanagi, M. Moriuchi, and H. Moriuchi. 2007. Does daily intake of bovine lactoferrin-containing products ameliorate rotaviral gastroenteritis? Acta Paediatr 96(8):1242- 1244.
[15] Ochoa, T. J., E. Chea-Woo, M. Campos, I. Pecho, A. Prada, R. J. McMahon, and T. G. Cleary. 2008. Impact of lactoferrin supplementation on growth and prevalence of Giardia colonization in children. Clin Infect Dis 46(12):1881-1883.
[16] Egashira, M., M. Moriuchi, and H. Moriuchi. 2009. Prevention of norovirus gastroenteritis in daycare centers with bovine lactoferrin-containing products. Abstract.
[17] 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. J Pediatr 162(2):349-356.
[18] Manzoni, P., M. Meyer, I. Stolfi, M. Rinaldi, S. Cattani, L. Pugni, M. G. Romeo, H. Messner, L.Decembrino, N. Laforgia, F. Vagnarelli, L. Memo, L. Bordignon, M. Maule, E. Gallo, M. Mostert,M. Quercia, L. Bollani, R. Pedicino, L. Renzullo, P. Betta, F. Ferrari, T. Alexander, R. Magaldi, D.Farina, F. Mosca, and M. Stronati. 2014. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. Early Hum Dev 90 Suppl 1:S60-65.