Acta Scientific Nutritional Health (ASNH)(ISSN: 2582-1423)

Review Article Volume 5 Issue 10

A Comprehensive Review on Functional Role and Additive Application of Lactoferrin

Barkha Binyameen1, Muhammad Abdul Rahim2, Waseem Khalid2*, Naqash Nasir2, Saleem Ilyas3, Fareed Afzal2, Muhammad Rehan4, Ravi Prakash Jha5, Anwar Ali6, Muhammad Zubair Khalid2, Zahra Maqbool2, Noman Aslam2, Muhammad Safwan Siddique2 and Hamza Israr2

1Institute of Plant Breeding and Biotechnology, Muhammad Nawaz Shareef University of Agriculture, Multan, Pakistan

2Department of Food Science, Government College University, Faisalabad, Pakistan

3Department of Food Technology, Government College of Technology, Faisalabad

4Institute of Agricultural Sciences, The Punjab University, Lahore, Pakistan

5Department of Community Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

6Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, China

*Corresponding Author: Waseem Khalid, Department of Food Science, Government College University Faisalabad, Pakistan.

Received: August 16, 2021; Published: September 16, 2021


  This review discusses the nutritional and biological properties of the LF. Lactoferrin [LF] is a multifunctional protein naturally present higher amount in milk and the lower amount is evaluated in rice and various secretions such as tears, saliva, pancreatic juice and bile. All existing non-animal LF expression systems have been improved from the point of view of their expression efficiency, purification procedure of target protein as well as the sophisticated cultivation, harvesting and biological activity. LF is used to activate humoral and cellular immune reactions. Therefore, it may be effective against COVID-19 and metabolic diseases. LF is an iron-binding glycoprotein that can be used to regulate iron absorption, also used as an antiviral and antibacterial agent in various food products. Furthermore, LF has been used for the formulation of infant feed and also used in pharmaceutical and nutraceutical industries. Moreover, LF is also used as an antioxidant and to protect against bacterial and viral infections. LF is very effective against many diseases caused by iron deficiency. Concluded that LF may inhibit iron absorption and can be used as a functional ingredient in many food products.

Keywords: Lactoferrin; Milk; COVID-19; Antiviral; Antibacterial


  1. Giansanti Francesco., et al. "Lactoferrin from milk: Nutraceutical and pharmacological properties”. Pharmaceuticals4 (2016): 61.
  2. Shams Homayoun., et al. "Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles”. The Journal of Immunology3 (2004): 1966-1977.
  3. Ashida Kinya., et al. "Cellular internalization of lactoferrin in intestinal epithelial cells”. Biometals3 (2004): 311-315.
  4. Wally Jeremy and Susan K Buchanan. "A structural comparison of human serum transferrin and human lactoferrin”. Biometals3 (2007): 249-262.
  5. El-Loly Mohamed Mansour and Mohamed Bahy Mahfouz. "Lactoferrin in Relation to Biological Functions and Applications: A”. International Journal of Dairy Science2 (2011): 79-111.
  6. Embleton Nicholas D., et al. "Lactoferrin: Antimicrobial activity and therapeutic potential”. Seminars in Fetal and Neonatal Medicine3 (2013).
  7. Chen Hong., et al. "Molecular cloning and functional expression of a chicken intestinal peptide transporter (cPepT1) in Xenopus oocytes and Chinese hamster ovary cells”. The Journal of Nutrition3 (2002): 387-393.
  8. Zarándi Márta and János Szolomájer. "Amino acids: chemistry, diversity and physical properties” (2017): 1-84.
  9. Valenti P and Giovanni Antonini. "Lactoferrin”. Cellular and Molecular Life Sciences22 (2005): 2576-2587.
  10. Mora Lagares Liadys., et al. "Homology modeling of the human p-glycoprotein (Abcb1) and insights into ligand binding through molecular docking studies”. International Journal of Molecular Sciences11 (2020): 4058.
  11. Lallemand Tanguy., et al. "An overview of duplicated gene detection methods: Why the duplication mechanism has to be accounted for in their choice”. Genes9 (2020): 1046.
  12. Bourne Philip E. "Life is three-dimensional, and it begins with molecules”. PLoS Biology3 (2017): e2002041.
  13. Baker Edward N., et al. "Lactoferrin and transferrin: functional variations on a common structural framework”. Biochemistry and Cell Biology1 (2002): 27-34
  14. Baker Heather M and Edward N Baker. "Lactoferrin and iron: structural and dynamic aspects of binding and release”. Biometals3 (2004): 209-216.
  15. Park Young W. “Bioactive components in milk and dairy products”. John Wiley and Sons (2009).
  16. Rodzik Agnieszka., et al. "Interactions of whey proteins with metal ions”. International Journal of Molecular Sciences6 (2020): 2156.
  17. Guo Maolin., et al. "TiIV uptake and release by human serum transferrin and recognition of TiIV-transferrin by cancer cells: understanding the mechanism of action of the anticancer drug titanocene dichloride”. Biochemistry33 (2000): 10023-10033.
  18. Steijns Jan M. "Milk ingredients as nutraceuticals”. International Journal of Dairy Technology3 (2001): 81-88.
  19. Cheng J B., et al. "Factors affecting the lactoferrin concentration in bovine milk”. Journal of Dairy Science3 (2008): 970-976.
  20. Chen L and X D Zeng. "Iron deficiency anemia-related factors and interventions”. Chinese Journal of Current Traditional and Western Medicine5 (2007): 423-424.
  21. Suzuki Yasushi A., et al. "Expression, characterization, and biologic activity of recombinant human lactoferrin in rice”. Journal of Pediatric Gastroenterology and Nutrition2 (2003): 190-199.
  22. Chong Daniel KX and William HR Langridge. "Expression of full-length bioactive antimicrobial human lactoferrin in potato plants”. Transgenic Research1 (2000): 71-78.
  23. Lipman Neil S., et al. "Monoclonal versus polyclonal antibodies: distinguishing characteristics, applications, and information resources”. ILAR Journal3 (2005): 258-268.
  24. Monzani Paulo S., et al. "Transgenic bovine as bioreactors: Challenges and perspectives”. Bioengineered3 (2016): 123-131.
  25. Sfeir Rose Mary., et al. "The mode of oral bovine lactoferrin administration influences mucosal and systemic immune responses in mice”. The Journal of nutrition2 (2004): 403-409.
  26. Chodaczek Grzegorz., et al. "A complex of lactoferrin with monophosphoryl lipid A is an efficient adjuvant of the humoral and cellular immune response in mice”. Medical microbiology and immunology4 (2006): 207-216.
  27. Fischer Romy., et al. "Regulation of physiological and pathological Th1 and Th2 responses by lactoferrin”. Biochemistry and Cell Biology3 (2006): 303-311.
  28. Dhennin‐Duthille Isabelle., et al. "Lactoferrin upregulates the expression of CD4 antigen through the stimulation of the mitogen‐activated protein kinase in the human lymphoblastic T Jurkat cell line”. Journal of Cellular Biochemistry4 (2000): 583-593.
  29. Yamauchi Koji., et al. "Bovine lactoferrin: benefits and mechanism of action against infections”. Biochemistry and Cell Biology3 (2006): 291-296.
  30. Curran Colleen S., et al. "Lactoferrin activates macrophages via TLR4-dependent and-independent signaling pathways”. Cellular Immunology1 (2006): 23-30.
  31. Kai Kenzo., et al. "Lactoferrin stimulates a Staphylococcus aureus killing activity of bovine phagocytes in the mammary gland”. Microbiology and Immunology3 (2002): 187-194.
  32. MAZURIER Joël., et al. "Expression of human lactotransferrin receptors in phytohemagglutinin‐stimulated human peripheral blood lymphocytes: Isolation of the receptors by antiligand‐affinity chromatography”. European Journal of Biochemistry2 (1989): 481-487.
  33. Rochard Elisabeth., et al. "The N-terminal domain I of human lactotransferrin binds specifically to phytohemagglutinin-stimulated peripheral blood human lymphocyte receptors”. FEBS Letters1 (1989): 201-204.
  34. Butler Thomas W., et al. "Immunoreactive lactoferrin in resting, activated, and neoplastic lymphocytes”. Leukemia Research5 (1990): 441-447.
  35. Siqueiros-Cendón Tania., et al. "Immunomodulatory effects of lactoferrin”. Acta Pharmacologica Sinica5 (2014): 557-566.
  36. Actor Jeffrey K., et al. "Lactoferrin as a natural immune modulator”. Current Pharmaceutical Design17 (2009): 1956-1973.
  37. Liu Kilia Y., et al. "Natural killer cell populations and cytotoxic activity in pigs fed mother’s milk, formula, or formula supplemented with bovine lactoferrin”. Pediatric Research4 (2013): 402-407.
  38. Mikogami Takashi., et al. "Effect of intracellular iron depletion by picolinic acid on expression of the lactoferrin receptor in the human colon carcinoma cell subclone HT29-18-C1”. Biochemical Journal2 (1995): 391-397.
  39. Medina Isabel., et al. "Effects of natural phenolic compounds on the antioxidant activity of lactoferrin in liposomes and oil-in-water emulsions”. Journal of Agricultural and Food Chemistry8 (2002): 2392-2399.
  40. Mulder Ann M., et al. "Bovine lactoferrin supplementation supports immune and antioxidant status in healthy human males”. Nutrition Research9 (2008): 583-589.
  41. Ruiz-Gimenez Pedro., et al. "Antihypertensive properties of lactoferricin B-derived peptides”. Journal of Agricultural and Food Chemistry11 (2010): 6721-6727.
  42. Ruiz-Giménez Pedro., et al. "Antihypertensive effect of a bovine lactoferrin pepsin hydrolysate: identification of novel active peptides”. Food Chemistry1 (2012): 266-273.
  43. Hayashida Ken-ichiro., et al. "Bovine lactoferrin has a nitric oxide-dependent hypotensive effect in rats”. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology2 (2004): R359-R365.
  44. Ruiz-Giménez Pedro., et al. "Bovine lactoferrin pepsin hydrolysate exerts inhibitory effect on angiotensin I-converting enzyme-dependent vasoconstriction”. International Dairy Journal10 (2007): 1212-1215
  45. Fernández-Musoles Ricardo., et al. "Lactoferricin B-derived peptides with inhibitory effects on ECE-dependent vasoconstriction”. Peptides10 (2010): 1926-1933.
  46. Pihlanto-Leppälä Anne., et al. "Angiotensin I-converting enzyme inhibitory properties of whey protein digests: concentration and characterization of active peptides”. Journal of Dairy Research1 (2000): 53-64.
  47. Fillebeen Carine., et al. "Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier”. Journal of Biological Chemistry11 (1999): 7011-7017.
  48. Hayashida Ken-ichiro., et al. "Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis”. Journal of Veterinary Medical Science2 (2004): 149-154.
  49. Kawakami Hiroshi., et al. "Effects of iron-saturated lactoferrin on iron absorption”. Agricultural and Biological Chemistry4 (1988): 903-908.
  50. Jenssen Håvard and Robert EW Hancock. "Antimicrobial properties of lactoferrin”. Biochimie1 (2009): 19-29.
  51. García-Montoya Isui Abril., et al. "Lactoferrin a multiple bioactive protein: an overview”. Biochimica et Biophysica Acta (BBA)-General Subjects3 (2012): 226-236.
  52. Reyes-Cortes Ruth., et al. "Antibacterial and cell penetrating effects of LFcin17–30, LFampin265–284, and LF chimera on enteroaggregative Escherichia coli”. Biochemistry and Cell Biology1 (2017): 76-81.
  53. González-Chávez Susana A., et al. "Lactoferrin: structure, function and applications”. International journal of Antimicrobial Agents4 (2009): 301-e1.
  54. Jenssen Håvard and Robert EW Hancock. "Antimicrobial properties of lactoferrin”. Biochimie1 (2009): 19-29.
  55. Redwan Elrashdy M., et al. "Potential lactoferrin activity against pathogenic viruses”. Comptes Rendus Biologies10 (2014): 581-595.
  56. Wakabayashi Hiroyuki., et al. "Lactoferrin for prevention of common viral infections”. Journal of Infection and Chemotherapy11 (2014): 666-671.
  57. Wong Jack Ho., et al. "A study of effects of peptide fragments of bovine and human lactoferrins on activities of three key HIV-1 enzymes”. Peptides62 (2014): 183-188.
  58. Wakabayashi Hiroyuki., et al. "Lactoferrin for prevention of common viral infections”. Journal of Infection and Chemotherapy11 (2014): 666-671.
  59. Vellingiri Balachandar., et al. "COVID-19: A promising cure for the global panic”. Science of the Total Environment725 (2020): 138277.
  60. Lan Jun., et al. "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor”. Nature7807 (2020): 215-220.
  61. Nitulescu George Mihai., et al. "Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies”. International Journal of Molecular Medicine2 (2020): 467-488.
  62. Van der Strate B W A., et al. "Antiviral activities of lactoferrin”. Antiviral Research3 (2001): 225-239.
  63. Redwan Elrashdy M., et al. "Potential lactoferrin activity against pathogenic viruses”. Comptes Rendus Biologies10 (2014): 581-595.
  64. Lang Jianshe., et al. "Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans”. PloS One8 (2011): e23710.
  65. Berlutti Francesca., et al. "Antiviral properties of lactoferrin—a natural immunity molecule”. Molecules8 (2011): 6992-7018.
  66. Legrand Dominique., et al. "Lactoferrin”. Cellular and Molecular Life Sciences22 (2005): 2549-2559.
  67. Giansanti Francesco., et al. "Lactoferrin from milk: Nutraceutical and pharmacological properties”. Pharmaceuticals4 (2016): 61.
  68. Ke Chen., et al. "Iron metabolism in infants: influence of bovine lactoferrin from iron-fortified formula”. Nutrition2 (2015): 304-309.
  69. Ziegler Ekhard E. "Consumption of cow's milk as a cause of iron deficiency in infants and toddlers”. Nutrition Reviews69 (2011): S37-S42.
  70. Eidelman Arthur I and Richard J Schanler. "Breastfeeding and the use of human milk”. Pediatrics (2012).
  71. Wang Xiaodan., et al. "Effects of recombinant human lactoferrin on improving the iron status of IDA rats”. Wei sheng yan jiu= Journal of Hygiene Research1 (2012): 13-17.
  72. Sherman Michael P. "Lactoferrin and necrotizing enterocolitis”. Clinics in Perinatology1 (2013): 79-91.
  73. Ke Chen., et al. "Iron metabolism in infants: influence of bovine lactoferrin from iron-fortified formula”. Nutrition2 (2015): 304-309.
  74. Wakabayashi Hiroyuki., et al. "Lactoferrin research, technology and applications”. International Dairy Journal11 (2006): 1241-1251.
  75. Tomita Mamoru., et al. "Twenty-five years of research on bovine lactoferrin applications”. Biochimie 1 (2009): 52-57.
  76. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). "Scientific Opinion on bovine lactoferrin”. EFSA Journal5 (2012): 2701.
  77. Wang Xiao., et al. "Research and development on lactoferrin and its derivatives in China from 2011–2015”. Biochemistry and Cell Biology1 (2017): 162-170.


Citation: Waseem Khalid., et al. “A Comprehensive Review on Functional Role and Additive Application of Lactoferrin". Acta Scientific Nutritional Health 5.10 (2021): 09-16.


Copyright: © 2021 Waseem Khalid., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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