Browse > Article
http://dx.doi.org/10.22424/jmsb.2019.37.3.167

Clinical Applications of Bioactive Milk Components: A Review  

Han, Rae Hee (Dept. of Animal Science and Technology, Chung-Ang University)
Yoon, Sung Hee (Dept. of Animal Science and Technology, Chung-Ang University)
Kim, Geun-Bae (Dept. of Animal Science and Technology, Chung-Ang University)
Publication Information
Journal of Dairy Science and Biotechnology / v.37, no.3, 2019 , pp. 167-176 More about this Journal
Abstract
Milk contains essential nutrients and functional compounds, such as calcium, fat-soluble vitamins A, D, E, and K, carotenoids, bioactive peptides, and sphingolipids. The bioactive molecules from milk are not expensive and have an added advantage of being derived from food. Therefore, they are more stable and have a broader spectrum than that of other chemicals. Bioactive milk components are useful for treating non-digestive tract disorders, such as cancer, cognitive decline, and hypertension. However, the clinical application of certain breast milk ingredients is limited due to the lack of a large-scale production technology. Once the scaled-up production of lactoferrin became possible, clinical applications were devised and evaluated. Similarly, human alpha-lactalbumin made lethal to tumor cells (HAMLET) can be produced on a large scale as a recombinant protein in microorganisms or in transgenic cattle using suitable separation systems. HAMLET can be used to treat human skin papilloma and cancer. Studies on breast milk that explored the clinical applications of the bioactive components of breast milk have spurred the development of translational medicine and breast milk-derived therapeutics. Some breast-milk derived therapeutic agents are already available to clinicians. Many components of breast milk have shown efficacy in pre-clinical studies and have valid clinical evaluations.
Keywords
milk oligosaccharide; milk fat; bioactive milk components; lactoferrin; ${\alpha}$-lactalbumin; phospholipid;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Nanthakumar N, Meng D, Goldstein AM, Zhu W, Lu L, Uauy R, et al. The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. PLoS One. 2011;6:e17776.   DOI
2 Klement E, Cohen RV, Boxman J, Joseph A, Reif S. Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis. Am J Clin Nutr. 2004;80:1342-1352.   DOI
3 Berlutti F, Pantanella F, Natalizi T, Frioni A, Paesano R, Polineni A, et al. Antiviral properties of lactoferrin: a natural immunity molecule. Molecules. 2011;16:6992-7018.   DOI
4 Brock JH. Lactoferrin: 50 years on. Biochem Cell Biol. 2012;90:245-251.   DOI
5 Hill DR, Newburg DS. Clinical applications of bioactive milk components. Nutr Rev. 2015;73:463-476.   DOI
6 Tawfeek HI, Najim NH, Al-Mashikhi S. Efficacy of an infant formula containing anti-Escherichia coli colostral antibodies from hyperimmunized cows in preventing diarrhea in infants and children: a field trial. Int J Infect Dis. 2003;7:120-128.   DOI
7 Otto W, Najnigier B, Stelmasiak T, Robins-Browne RM. Randomized control trials using a tablet formulation of hyperimmune bovine colostrum to prevent diarrhea caused by enterotoxigenic Escherichia coli in volunteers. Scand J Gastroenterol. 2011;46:862-868.   DOI
8 Ochoa TJ, Chea-Woo E, Baiocchi N, Pecho I, Campos M, Prada A, et al. Randomized double-blind controlled trial of bovine lactoferrin for prevention of diarrhea in children. J Pediatr. 2013;162:349-356.   DOI
9 Laffan AM, McKenzie R, Forti J, Conklin D, Marcinko R, Shrestha R, et al. Lactoferrin for the prevention of post-antibiotic diarrhoea. J Health Popul Nutr. 2011;29:547-51.
10 Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. J Am Med Assoc. 2009;302:1421-1428.   DOI
11 Manzoni P, Stolfi I, Messner H, Cattani S, Laforgia N, Romeo MG, et al. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial. Pediatrics. 2012;129:116-123.   DOI
12 Parente F, Cucino C, Anderloni A, Grandinetti G, Bianchi Porro G. Treatment of Helicobacter pylori infection using a novel antiadhesion compound (3'sialyllactose sodium salt). A double blind, placebo-controlled clinical study. Helicobacter. 2003;8:252-256.   DOI
13 Guntupalli K, Dean N, Morris PE, Bandi V, Margolis B, Rivers E, et al. A phase 2 randomized, double-blind, placebo-controlled study of the safety and efficacy of talactoferrin in patients with severe sepsis. Crit Care Med. 2013;41:706-716.   DOI
14 de Bortoli N, Leonardi G, Ciancia E, Merlo A, Bellini M, Costa F, et al. Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J Gastroenterol. 2007;102:951-956.   DOI
15 Kaito M, Iwasa M, Fujita N, Kobayashi Y, Kojima Y, Ikoma J, et al. Effect of lactoferrin in patients with chronic hepatitis C: combination therapy with interferon and ribavirin. J Gastroenterol Hepatol. 2007;22:1894-1897.   DOI
16 Edde L, Hipolito RB, Hwang FF, Headon DR, Shalwitz RA, Sherman MP. Lactoferrin protects neonatal rats from gut-related systemic infection. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1140-G1150.   DOI
17 King JC Jr, Cummings GE, Guo N, Trivedi L, Readmond BX, Keane V, et al. A double-blind, placebo-controlled, pilot study of bovine lactoferrin supplementation in bottle-fed infants. J Pediatr Gastroenterol Nutr. 2007;44:245-251.   DOI
18 Zavaleta N, Figueroa D, Rivera J, Sanchez J, Alfaro S, Lonnerdal B. Efficacy of rice-based oral rehydration solution containing recombinant human lactoferrin and lysozyme in Peruvian children with acute diarrhea. J Pediatr Gastroenterol Nutr. 2007;44:258-64.   DOI
19 Tung YT, Chen HL, Yen CC, Lee PY, Tsai HC, Lin MF, et al. Bovine lactoferrin inhibits lung cancer growth through suppression of both inflammation and expression of vascular endothelial growth factor. J Dairy Sci. 2013;96:2095-2106.   DOI
20 Vitetta L, Coulson S, Beck SL, Gramotnev H, Du S, Lewis S. The clinical efficacy of a bovine lactoferrin/whey protein Ig-rich fraction (Lf/IgF) for the common cold: a double blind randomized study. Complement Ther Med. 2013;21:164-171.   DOI
21 Digumarti R, Wang Y, Raman G, Doval DC, Advani SH, Julka PK, et al. A randomized, double-blind, placebo-controlled, phase II study of oral talactoferrin in combination with carboplatin and paclitaxel in previously untreated locally advanced or metastatic non-small cell lung cancer. J Thorac Oncol. 2011;6:1098-1103.   DOI
22 Kozu T, Iinuma G, Ohashi Y, Saito Y, Akasu T, Saito D, et al. Effect of orally administered bovine lactoferrin on the growth of adenomatous colorectal polyps in a randomized, placebo-controlled clinical trial. Cancer Prev Res. 2009;2:975-983.   DOI
23 Sun X, Jiang R, Przepiorski A, Reddy S, Palmano KP, Krissansen GW. "Ironsaturated" bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice. BMC Cancer. 2012;12:591.   DOI
24 Engfer MB, Stahl B, Finke B, Sawatzki G, Daniel H. Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am J Clin Nutr. 2000;71:1589-96.   DOI
25 Bode L. Recent advances on structure, metabolism, and function of human milk oligosaccharides. J Nutr. 2006;136:2127-2130.   DOI
26 Newburg DS, Walker WA. Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatr Res. 2007;61:2-8.   DOI
27 Eiwegger T, Stahl B, Schmitt J, Boehm G, Gerstmayr M, Pichler J, et al. Human milk-derived oligosaccharides and plant-derived oligosaccharides stimulate cytokine production of cord blood T-cells in vitro. Pediatr Res. 2004;56:536-540.   DOI
28 Crane JK, Azar SS, Stam A, Newburg DS. Oligosaccharides from human milk block binding and activity of the Escherichia coli heat-stable enterotoxin (STa) in T84 intestinal cells. J Nutr. 1994;124:2358-2364.   DOI
29 Atochina O, Harn D. LNFPIII/LeX-stimulated macrophages activate natural killer cells via CD40-CD40L interaction. Clin Diagn Lab Immunol. 2005;12:1041-1049.   DOI
30 Terrazas LI, Walsh KL, Piskorska D, McGuire E, Harn DA Jr. The schistosome oligosaccharide lacto-N-neotetraose expands Gr1(+) cells that secrete anti-inflammatory cytokines and inhibit proliferation of naive CD4(+) cells: a potential mechanism for immune polarization in helminth infections. J Immunol. 2001;167:5294-5303.   DOI
31 Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22:1147-1162.   DOI
32 Bode L, Kunz C, Muhly-Reinholz M, Mayer K, Seeger W, Rudloff S. Inhibition of monocyte, lymphocyte, and neutrophil adhesion to endothelial cells by human milk oligosaccharides. Thromb Haemost. 2004;92:1402-1410.   DOI
33 Bode L, Rudloff S, Kunz C, Strobel S, Klein N. Human milk oligosaccharides reduce platelet neutrophil complex formation leading to a decrease in neutrophil 2 integrin expression. J Leukoc Biol. 2004;76:820-826.   DOI
34 Thompson AM, Bizzarro MJ. Necrotizing enterocolitis in newborns: pathogenesis, prevention and management. Drugs. 2008;68:1227-1238.   DOI
35 Bollyky PL, Wu RP, Falk BA, Lord JD, Long SA, Preisinger A, et al. ECM components guide IL-10 producing regulatory T-cell (TR1) induction from effector memory T-cell precursors. Proc Natl Acad Sci USA. 2011;108:7938-7943.   DOI
36 Jantscher-Krenn E, Zherebtsov M, Nissan C, Goth K, Guner YS, Naidu N, et al. The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. Gut. 2012;61:1417-1425.   DOI
37 Frey H, Schroeder N, Manon-Jensen T, Iozzo RV, Schaefer L. Biological interplay between proteoglycans and their innate immune receptors in inflammation. Fed Eur Biochem Soc J. 2013;280:2165-2179.
38 Coppa GV, Zampini L, Galeazzi T, Facinelli B, Ferrante L, Capretti R, et al. Human milk oligosaccharides inhibit the adhesion to Caco-2 cells of diarrheal pathogens: Escherichia coli, Vibrio cholerae, and Salmonella fyris. Pediatr Res. 2006;59:377-382.   DOI
39 Russo E, Scicchitano F, Citraro R, Aiello R, Camastra C, Mainardi P, et al. Protective activity of ${\alpha}$-lactoalbumin (ALAC), a whey protein rich in tryptophan, in rodent models of epileptogenesis. Neuroscience. 2012;226:282-288.   DOI
40 Riehl TE, Foster L, Stenson, WF. Hyaluronic acid is radioprotective in the intestine through a TLR4 and COX-2-mediated mechanism. Am J Physiol Gastrointest Liver Physiol. 2012;302:G309-G316.   DOI
41 Citraro R, Scicchitano F, De Fazio S, Raggio R, Mainardi P, Perucca E, et al. Preclinical activity profile of ${\alpha}$-lactoalbumin, a whey protein rich in tryptophan, in rodent models of seizures and epilepsy. Epilepsy Res. 2011;95:60-69.   DOI
42 Hakansson A, Zhivotovsky B, Orrenius S, Sabharwal H, Svanborg C. Apoptosis induced by a human milk protein. Proc Natl Acad Sci USA. 1995;92:8064-8068.   DOI
43 Duringer C, Hamiche A, Gustafsson L, Kimura H, Svanborg C. HAMLET interacts with histones and chromatin in tumor cell nuclei. J Biol Chem. 2003;278:42131-42135.   DOI
44 Gustafsson L, Aits S, Onnerfjord P, Trulsson M, Storm P, Svanborg C. Changes in proteasome structure and function caused by HAMLET in tumor cells. PloS One. 2009;4:e5229.   DOI
45 Mossberg AK, Hun Mok K, Morozova-Roche LA, Svanborg C. Structure and function of human ${\alpha}$-lactalbumin made lethal to tumor cells (HAMLET)-type complexes. Fed Eur Biochem Soc J. 2010;277:4614-4625.
46 Castro-Gomez MP, Holgado F, Rodriguez-Alcala LM, Montero O, Fontecha J. Comprehensive study of the lipid classes of krill oil by fractionation and identification of triacylglycerols, diacylglycerols, and phospholipid molecular species by using UPLC/QToF-MS. Food Anal Methods. 2015;8:2568-2580.   DOI
47 Fischer W, Gustafsson L, Mossberg AK, Gronli J, Mork S, Bjerkvig R, et al. Human ${\alpha}$-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival. Cancer Res. 2004;64:2105-2112.   DOI
48 Mossberg AK, Wullt B, Gustafsson L, Mansson W, Ljunggren E, Svanborg C. Bladder cancers respond to intravesical instillation of HAMLET (human ${\alpha}$-lactalbumin made lethal to tumor cells). Int J Cancer. 2007;121:1352-1359.   DOI
49 Zhang Y, Luo J, Bi J, Wang J, Sun L, Liu Y, et al. Efficient separation of homologous ${\alpha}$-lactalbumin from transgenic bovine milk using optimized hydrophobic interaction chromatography. J Chromatogr A. 2010;1217:3668-3673.   DOI
50 Guo Z, Vikbjerg AF, Xu X. Enzymatic modification of phospholipids for functional applications and human nutrition. Biotechnol Adv. 2005;23:203-259.   DOI
51 Li J, Ren S, Piao HL, Wang F, Yin P, Xu C, et al. Integration of lipidomics and transcriptomics unravels aberrant lipid metabolism and defines cholesteryl oleate as potential biomarker of prostate cancer. Sci Rep. 2016;6:20984.   DOI
52 Zanabria R, Tellez AM, Griffiths M, Corredig M. Milk fat globule membrane isolate induces apoptosis in HT-29 human colon cancer cells. Food Funct. 2013;4:222-230.   DOI
53 Rosqvist F, Smedman A, Lindmark-Mansson H, Paulsson M, Petrus P, Straniero S, et al. Potential role of milk fat globule membrane in modulating plasma lipoproteins, gene expression, and cholesterol metabolism in humans: a randomized study. Am J Clin Nutr. 2015;102:20-30.   DOI
54 Patwardhan GA, Liu YY. Sphingolipids and expression regulation of genes in cancer. Prog Lipid Res. 2011;50:104-114.   DOI
55 Snow DR, Jimenez-Flores R, Ward RE, Cambell J, Young MJ, Nemere I, et al. Dietary milk fat globule membrane reduces the incidence of aberrant crypt foci in Fischer-344 rats. J Agric Food Chem. 2010;58:2157-2163.   DOI