Emerging Health Properties of Whey Proteins and Their Clinical Implications

REFERENCES

• Murakami K, Lagarde M, Yuki Y: Identification of minor proteins of human colostrum and mature milk by two-dimensional electrophoresis. Electrophoresis19 :2521– 2527,1998 .
   PubMed Web of Science ®Google Scholar
• Yamada M, Murakami K, Wallingford JC, Yuki Y: Identification of low-abundance proteins of bovine colostral and mature milk using two-dimensional electrophoresis followed by microsequencing and mass spectrometry. Electrophoresis23 :1153– 1160,2002 .
   PubMed Web of Science ®Google Scholar
• Palmer DJ, Kelly VC, Smit AM, Kuy S, Knight CG, Cooper GJ: Human colostrum: identification of minor proteins in the aqueous phase by proteomics. Proteomics6 :2208– 2216,2006 .
   PubMed Web of Science ®Google Scholar
• Huth PJ, DiRenzo DB, Miller GD: Major scientific advances with dairy foods in nutrition and health. J Dairy Sci89 :1207– 1221,2006 .
   PubMed Web of Science ®Google Scholar
• Papenburg R, Bounous G, Fleiszer D, Gold P: Dietary milk proteins inhibit the development of dimethylhydrazine-induced malignancy. Tumor Biol11 :129– 136,1990 .
   PubMed Web of Science ®Google Scholar
• Bounous G, Gervais F, Amer V, Batist G, Gold P: The influence of dietary whey protein on tissue glutathione and the diseases of aging. Clin Invest Med12 :343– 349,1989 .
   PubMed Web of Science ®Google Scholar
• Costantino AM, Balzola F, Bounous G: Changes in biliary secretory immunoglobulins A in mice fed whey proteins. Minerva Dietol Gastroenterol35 :241– 245,1989 .
   PubMedGoogle Scholar
• Aoe S, Toba Y, Yamamura J, Kawakami H, Yahiro M, Kumegawa M, Itabashi A, Takada Y: Controlled trial of the effects of milk basic protein (MBP) supplementation on bone metabolism in healthy adult women. Biosci Biotechnol Biochem65 :913– 918,2001 .
   PubMed Web of Science ®Google Scholar
• Kruger MC, Plimmer GG, Schollum LM, Haggarty N, Ram S, Palmano K: The effect of whey acidic protein fractions on bone loss in the ovariectomised rat. Br J Nutr94 :244– 252,2005 .
   PubMedGoogle Scholar
• Bounous G, Kongshavn PA: Differential effect of dietary protein type on the B-cell and T-cell immune responses in mice. J Nutr115 :1403– 1408,1985 .
   PubMed Web of Science ®Google Scholar
• Rosaneli CF, Bighetti AE, Antonio MA, Carvalho JE, Sgarbieri VC: Efficacy of a whey protein concentrate on the inhibition of stomach ulcerative lesions caused by ethanol ingestion. J Med Food5 :221– 228,2002 .
   PubMedGoogle Scholar
• Rosaneli CF, Bighetti AE, Antonio MA, Carvalho JE, Sgarbieri VC: Protective effect of bovine milk whey protein concentrate on the ulcerative lesions caused by subcutaneous administration of indomethacin. J Med Food7 :309– 314,2004 .
   PubMed Web of Science ®Google Scholar
• Frid AH, Nilsson M, Holst JJ, Bjorck IM: Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am J Clin Nutr82 :69– 75,2005 .
   PubMed Web of Science ®Google Scholar
• Wolber FM, Broomfield AM, Fray L, Cross ML, Dey D: Supplemental dietary whey protein concentrate reduces rotavirus-induced disease symptoms in suckling mice. J Nutr135 :1470– 1474,2005 .
   PubMedGoogle Scholar
• Vegarud GE, Langsrud T, Svenning C: Mineral-binding milk proteins and peptides; occurrence, biochemical and technological characteristics. Br J Nutr84(Suppl 1) :S91– 98,2000 .
   Google Scholar
• Perez MD, Sanchez L, Aranda P, Ena JM, Oria R, Calvo M: Effect of beta-lactoglobulin on the activity of pregastric lipase. A possible role for this protein in ruminant milk. Biochim Biophys Acta1123 :151– 155,1992 .
   PubMedGoogle Scholar
• Kushibiki S, Hodate K, Kurisaki J, Shingu H, Ueda Y, Watanabe A, Shinoda M: Effect of beta-lactoglobulin on plasma retinol and triglyceride concentrations, and fatty acid composition in calves. J Dairy Res68 :579– 586,2001 .
   PubMedGoogle Scholar
• Perez MD, Calvo M: Interaction of beta-lactoglobulin with retinol and fatty acids and its role as a possible biological function for this protein: a review. J Dairy Sci78 :978– 988,1995 .
   PubMed Web of Science ®Google Scholar
• Yoshida T, Sasahara Y, Miyakawa S, Hattori M: Reduced T cell response to beta-lactoglobulin by conjugation with acidic oligosaccharides. J Agric Food Chem53 :6851– 6857,2005 .
   PubMed Web of Science ®Google Scholar
• Adel-Patient K, Ah-Leung S, Creminon C, Nouaille S, Chatel JM, Langella P, Wal JM: Oral administration of recombinant Lactococcus lactis expressing bovine beta-lactoglobulin partially prevents mice from sensitization. Clin Exp Allergy35 :539– 546,2005 .
   PubMed Web of Science ®Google Scholar
• Cortes-Perez NG, Ah-Leung S, Bermudez-Humaran LG, Corthier G, Wal JM, Langella P, Adel-Patient K: Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice. Clin Vaccine Immunol14 :226– 233,2007 .
   PubMed Web of Science ®Google Scholar
• Prioult G, Pecquet S, Fliss I: Stimulation of interleukin-10 production by acidic beta-lactoglobulin-derived peptides hydrolyzed with Lactobacillus paracasei NCC2461 peptidases. Clin Diagn Lab Immunol11 :266– 271,2004 .
   PubMedGoogle Scholar
• Meisel H: Biochemical properties of peptides encrypted in bovine milk proteins. Curr Med Chem12 :1905– 1919,2005
   PubMed Web of Science ®Google Scholar
• FitzGerald RJ, Meisel H: Lactokinins: whey protein-derived ACE inhibitory peptides. Nahrung43 :165– 167,1999 .
   PubMedGoogle Scholar
• Sipola M, Finckenberg P, Vapaatalo H, Pihlanto-Leppala A, Korhonen H, Korpela R, Nurminen ML: Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats. Life Sci71 :1245– 1253,2002 .
   PubMed Web of Science ®Google Scholar
• Yamauchi R, Wada E, Yamada D, Yoshikawa M, Wada K: Effect of beta-lactotensin on acute stress and fear memory. Peptides27 :3176– 3182,2006 .
   PubMedGoogle Scholar
• Yamauchi R, Sonoda S, Jinsmaa Y, Yoshikawa M: Antinociception induced by beta-lactotensin, a neurotensin agonist peptide derived from beta-lactoglobulin, is mediated by NT2 and D1 receptors. Life Sci73 :1917– 1923,2003 .
   PubMedGoogle Scholar
• Ohinata K, Sonoda S, Inoue N, Yamauchi R, Wada K, Yoshikawa M: beta-Lactotensin, a neurotensin agonist peptide derived from bovine beta-lactoglobulin, enhances memory consolidation in mice. Peptides28 :1470– 1474,2007 .
   PubMed Web of Science ®Google Scholar
• Yamauchi R, Ohinata K, Yoshikawa M: Beta-lactotensin and neurotensin rapidly reduce serum cholesterol via NT2 receptor. Peptides24 :1955– 1961,2003 .
   PubMed Web of Science ®Google Scholar
• McIntosh GH, Royle P, Le Leu RK, Regester GO, Johnson M, Grinsted RL, Kenward RS, Smithers GW: Whey proteins as functional food ingredients? Int Dairy J8 :425– 434,1998 .
   Web of Science ®Google Scholar
• Thompson MP, Farrell HM, Mohanam S, Liu S, Kidwell WR, Bansal MP, Cook RG, Medina D, Kotts CE, Bano M: Identification of human milk α-lactalbumin as a cell growth inhibitor. Protoplasma167 :134– 144,1992 .
   Web of Science ®Google Scholar
• Wong CW, Seow HF, Husband AJ, Regester GO, Watson DL: Effects of purified bovine whey factors on cellular immune functions in ruminants. Vet Immunol Immunopathol56 :85– 96,1997 .
   PubMed Web of Science ®Google Scholar
• Kayser H, Meisel H: Stimulation of human peripheral blood lymphocytes by bioactive peptides derived from bovine milk proteins. FEBS Lett383 :18– 20,1996 .
   PubMed Web of Science ®Google Scholar
• Jaziri M, Migliore-Samour D, Casabianca-Pignede MR, Keddad K, Morgat JL, Jolles P: Specific binding sites on human phagocytic blood cells for Gly-Leu-Phe and Val-Glu-Pro-Ile-Pro-Tyr, immunostimulating peptides from human milk proteins. Biochim Biophys Acta1160 :251– 261,1992 .
   PubMed Web of Science ®Google Scholar
• Migliore-Samour D, Roch-Arveiller M, Tissot M, Jazziri M, Keddad K, Giroud JP, Jolles P: Effects of tripeptides derived from milk proteins on polymorphonuclear oxidative and phosphoinositide metabolisms. Biochem Pharmacol44 :673– 680,1992 .
   PubMedGoogle Scholar
• Gattegno L, Migliore-Samour D, Saffar L, Jollts P: Enhancement of phagocytic activity of human monocytic-macrophagic cells by immunostimulating peptides from human casein. Immunol Lett18 :27– 32,1988 .
   PubMed Web of Science ®Google Scholar
• Berthou J, Migliore-Samour D, Lifchitz A, Delettre J, Floc'h F, Jolles P: Immunostimulating properties and three-dimensional structure of two tripeptides from human and cow caseins. FEBS Lett218 :55– 58,1987 .
   PubMed Web of Science ®Google Scholar
• Sternhagen LG, Allen JC: Growth rates of a human colon adenocarcinoma cell line are regulated by the milk protein alpha-lactalbumin. Adv Exp Med Biol501 :115– 120,2001 .
   PubMed Web of Science ®Google Scholar
• Svanborg C, Agerstam H, Aronson A, Bjerkvig R, Duringer C, Fischer W, Gustafsson L, Hallgren O, Leijonhuvud I, Linse S, Mossberg AK, Nilsson H, Pettersson J, Svensson M: HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects. Adv Cancer Res88 :1– 29,2003 .
   PubMed Web of Science ®Google Scholar
• Gustafsson L, Hallgren O, Mossberg AK, Pettersson J, Fischer W, Aronsson A, Svanborg C: HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy. J Nutr135 :1299– 1303,2005 .
   PubMed Web of Science ®Google Scholar
• Gustafsson L, Leijonhufvud I, Aronsson A, Mossberg AK, Svanborg C: Treatment of skin papillomas with topical alpha-lactalbumin-oleic acid. N Engl J Med350 :2663– 2672,2004 .
   PubMed Web of Science ®Google Scholar
• Markus CR, Jonkman LM, Lammers JH, Deutz NE, Messer MH, Rigtering N: Evening intake of alpha-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention. Am J Clin Nutr81 :1026– 33,2005 .
   PubMed Web of Science ®Google Scholar
• Orosco M, Rouch C, Beslot F, Feurte S, Regnault A, Dauge V: Alpha-lactalbumin-enriched diets enhance serotonin release and induce anxiolytic and rewarding effects in the rat. Behav Brain Res148 :1– 10,2004 .
   PubMed Web of Science ®Google Scholar
• Matsumoto H, Shimokawa Y, Ushida Y, Toida T, Hayasawa H: New biological function of bovine alpha-lactalbumin: protective effect against ethanol- and stress-induced gastric mucosal injury in rats. Biosci Biotechnol Biochem65 :1104– 1111,2001 .
   PubMed Web of Science ®Google Scholar
• Jazziri M, Tsuruki T, Yoshikawa M: Anti-alopecia effect of Gly-Leu-Phe, an immunostimulating peptide derived from alpha-lactalbumin. Biosci Biotechnol Biochem69 :1633– 1635,2005 .
   PubMed Web of Science ®Google Scholar
• Bruck WM, Kelleher SL, Gibson GR, Graverholt G, Lonnerdal BL: The effects of alpha-lactalbumin and glycomacropeptide on the association of CaCo-2 cells by enteropathogenic Escherichia coli, Salmonella typhimurium and Shigella flexneri. FEMS Microbiol Lett259 :158– 162,2006 .
   PubMed Web of Science ®Google Scholar
• Yvon M, Beucher S, Guilloteau P, Le Huerou-Luron I, Corring T: Effects of caseinomacropeptide (CMP) on digestion regulation. Reprod Nutr Dev34 :527– 537,1994 .
   PubMedGoogle Scholar
• Beucher S, Levenez F, Yvon M, Corring T: Effect of caseinomacropeptide (CMP) on cholecystokinin (CCK) release in rat. Reproduction Nutr Dev34 :613– 614,1994 .
   Google Scholar
• Corring T, Beaufrere B, Maubois JL: Release of cholecystokinin in humans after ingestion of glycomacropeptide (GMP). Paper presented at the 1997 International Whey Conference, Rosemont, IL.
   Google Scholar
• Gustafson DR, McMahon DJ, Morrey J, Nan R: Appetite is not influenced by a unique milk peptide: caseinomacropeptide (CMP). Appetite36 :157– 163,2001 .
   PubMed Web of Science ®Google Scholar
• Otani H, Monnai M, Kawasaki Y, Kawakami H, Tanimoto M: Inhibition of mitogen-induced proliferative responses of lymphocytes by bovine k-caseinoglycopeptides having different carbohydrate chains. J Dairy Res62 :349– 357,1995 .
   PubMed Web of Science ®Google Scholar
• Monnai M, Otani H: Effect of bovine k-caseinoglycopeptide on secretion of interleukin-1 family cytokines by P388D1 cells, a line derived from mouse monocyte/macrophage. Milchwissenschaft52 :192– 196,1997 .
   Web of Science ®Google Scholar
• Daddaoua A, Puerta V, Zarzuelo A, Suarez MD, Sanchez de Medina F, Martinez-Augustin O: Bovine glycomacropeptide is anti-inflammatory in rats with hapten-induced colitis. J Nutr135 :1164– 1170,2005 .
   PubMed Web of Science ®Google Scholar
• Li EW, Mine Y: Immunoenhancing effects of bovine glycomacropeptide and its derivatives on the proliferative response and phagocytic activities of human macrophagelike cells, U937. J Agric Food Chem52 :2704– 2708,2004 .
   PubMed Web of Science ®Google Scholar
• Kelleher SL, Chatterton D, Nielsen K, Lonnerdal B: Glycomacropeptide and alpha-lactalbumin supplementation of infant formula affects growth and nutritional status in infant rhesus monkeys. Am J Clin Nutr77 :1261– 1268,2003 .
   PubMed Web of Science ®Google Scholar
• Brody EP: Biological activities of bovine glycomacropeptide. Br J Nutr84(Suppl 1) :S39– 46,2000 .
   Google Scholar
• Nakajima K, Tamura N, Kobayashi-Hattori K, Yoshida T, Hara-Kudo Y, Ikedo M, Sugita-Konishi Y, Hattori M: Prevention of intestinal infection by glycomacropeptide. Biosci Biotechnol Biochem69 :2294– 2301,2005 .
   PubMed Web of Science ®Google Scholar
• Wang B, Yu B, Karim M, Hu H, Sun Y, McGreevy P, Petocz P, Held S, Brand-Miller J: Dietary sialic acid supplementation improves learning and memory in piglets. Am J Clin Nutr85 :561– 569,2007 .
   PubMed Web of Science ®Google Scholar
• Sorensen ES, Petersen TE: Purification and characterization of three proteins isolated from the proteose peptone fraction of bovine milk. J Dairy Res60 :189– 197,1993 .
   PubMedGoogle Scholar
• Sugahara T, Onda H, Shinohara Y, Horii M, Akiyama K, Nakamoto K, Hara K: Immunostimulation effects of proteose-peptone component 3 fragment on human hybridomas and peripheral blood lymphocytes. Biochim Biophys Acta1725 :233– 240,2005 .
   PubMedGoogle Scholar
• Campagna S, Mathot AG, Fleury Y, Girardet JM, Gaillard JL: Antibacterial activity of lactophoricin, a synthetic 23-residues peptide derived from the sequence of bovine milk component-3 of proteose peptone. J Dairy Sci87 :1621– 1626,2004 .
   PubMed Web of Science ®Google Scholar
• Korhonen H, Marnila P, Gill HS: Bovine milk antibodies for health. Br J Nutr84(Suppl 1) :S135– 146,2000 .
   Google Scholar
• Zenk JL, Helmer TR, Kuskowski MA: The effects of milk protein concentrate on the symptoms of osteoarthritis in adults: An exploratory, randomized, double-blind, placebo-controlled trial. Curr Ther Res63 :430– 442,2002 .
   Web of Science ®Google Scholar
• Laursen I, Briand P, Lykkesfeldt AE: Serum albumin as a modulator on growth of the human breast cancer cell line, MCF-7. Anticancer Res10 :343– 352,1990 .
   PubMed Web of Science ®Google Scholar
• Bosselaers IEM, Caessens PWJR, van Boekel MAJS, Alink GM: Differential effects of milk proteins, BSA and soy protein on 4NQO- or MNNG-induced SCEs in V79 cells. Food Chem Toxicol32 :905– 909,1994 .
   PubMed Web of Science ®Google Scholar
• Ohinata K, Inui A, Asakawa A, Wada K, Wada E, Yoshikawa M: Albutensin A and complement C3a decrease food intake in mice. Peptides23 :127– 133,2002 .
   PubMed Web of Science ®Google Scholar
• Rogers ML, Goddard C, Regester GO, Ballard FJ, Belford DA: Transforming growth factor beta in bovine milk: concentration, stability and molecular mass forms. J Endocrinol151 :77– 86,1996 .
   PubMed Web of Science ®Google Scholar
• Kelly GS: Bovine colostrums: a review of clinical uses. Altern Med Rev8 :378– 394,2003 .
   PubMedGoogle Scholar
• Ward PP, Paz E, Conneely OM: Multifunctional roles of lactoferrin: a critical overview. Cell Mol Life Sci62 :2540– 2548,2005 .
   PubMed Web of Science ®Google Scholar
• Cornish J, Callon KE, Naot D, Palmano KP, Banovic T, Bava U, Watson M, Lin JM, Tong PC, Chen Q, Chan VA, Reid HE, Fazzalari N, Baker HM, Baker EN, Haggarty NW, Grey AB, Reid IR: Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo. Endocrinology145 :4366– 4374,2004 .
   PubMed Web of Science ®Google Scholar
• Zimecki M, Mazurier J, Spik G, Kapp JA: Lactoferrin inhibits proliferative response and cytokine production of TH1 but not TH2 cell lines. Arch Immunol Ther Exp (Warsz)44 :51– 56,1996 .
   PubMedGoogle Scholar
• Zimecki M, Mazurier J, Spik G, Kapp JA: Human lactoferrin induces phenotypic and functional changes in murine splenic B cells. Immunology86 :122– 127,1995 .
   PubMed Web of Science ®Google Scholar
• Szuster-Ciesielska A, Kaminska T, Kandefer-Szerszen M: Phagocytosis-enhancing effect of lactoferrin on bovine peripheral blood monocytes in vitro and in vivo. Arch Vet Pol35 :63– 71,1995 .
   PubMedGoogle Scholar
• Miyauchi H, Hashimoto S, Nakajima M, Shinoda I, Fukuwatari Y, Hayasawa H: Bovine lactoferrin stimulates the phagocytic activity of human neutrophils: identification of its active domain. Cell Immunol187 :34– 37,1998 .
   PubMed Web of Science ®Google Scholar
• Shinoda I, Takase M, Fukuwatari Y, Shimamura S, Koller M, Konig W: Effects of lactoferrin and lactoferricin on the release of interleukin 8 from human polymorphonuclear leukocytes. Biosci Biotechnol Biochem60 :521– 523,1996 .
   PubMed Web of Science ®Google Scholar
• Wong CW, Liu AH, Regester GO, Francis GL, Watson DL: Influence of whey and purified whey proteins on neutrophil functions in sheep. J Dairy Res64 :281– 288,1997 .
   PubMedGoogle Scholar
• Sakai T, Banno Y, Kato Y, Nozawa Y, Kawaguchi M: Pepsin-digested bovine lactoferrin induces apoptotic cell death with JNK/SAPK activation in oral cancer cells. J Pharmacol Sci98 :41– 48,2005 .
   PubMed Web of Science ®Google Scholar
• Mader JS, Salsman J, Conrad DM, Hoskin DW: Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Mol Cancer Ther4 :612– 624,2005 .
   PubMed Web of Science ®Google Scholar
• Wakabayashi H, Takakura N, Yamauchi K, Tamura Y: Modulation of immunity-related gene expression in small intestines of mice by oral administration of lactoferrin. Clin Vaccine Immunol13 :239– 245,2006 .
   PubMed Web of Science ®Google Scholar
• Yamauchi K, Wakabayashi H, Hashimoto S, Teraguchi S, Hayasawa H, Tomita MR: Effects of orally administered bovine lactoferrin on the immune system of healthy volunteers. Adv Exp Med Biol443 :261– 265,1998 .
   PubMed Web of Science ®Google Scholar
• Zimecki M, Spiegel K, Wlaszczyk A, Kubler A, Kruzel ML: Lactoferrin increases the output of neutrophil precursors and attenuates the spontaneous production of TNF-alpha and IL-6 by peripheral blood cells. Arch Immunol Ther Exp (Warsz)47 :113– 118,1999 .
   PubMedGoogle Scholar
• Wakabayashi H, Takakura N, Teraguchi S, Tamura Y: Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Microbiol Immunol47 :37– 43,2003 .
   PubMed Web of Science ®Google Scholar
• Zimecki M, Artym J, Chodaczek G, Kocieba M, Kruzel M: Effects of lactoferrin on the immune response modified by the immobilization stress. Pharmacol Rep57 :811– 817,2005 .
   PubMed Web of Science ®Google Scholar
• Ushida Y, Sekine K, Kuhara T, Takasuka N, Iigo M, Maeda M, Tsuda H: Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat. Jpn J Cancer Res90 :262– 267,1999 .
   PubMedGoogle Scholar
• Iigo M, Kuhara T, Ushida Y, Sekine K, Moore MA, Tsuda H: Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice. Clin Exp Metastasis17 :35– 40,1999 .
   PubMed Web of Science ®Google Scholar
• Artym J, Zimecki M, Kuryszko J, Kruzel ML: Lactoferrin accelerates reconstitution of the humoral and cellular immune response during chemotherapy-induced immunosuppression and bone marrow transplant in mice. Stem Cells Dev14 :548– 555,2005 .
   PubMedGoogle Scholar
• Artym J, Zimecki M, Kruzel ML: Effect of lactoferrin on the methotrexate-induced suppression of the cellular and humoral immune response in mice. Anticancer Res24 :3831– 3836,2004 .
   PubMedGoogle Scholar
• Artym J, Zimecki M, Paprocka M, Kruzel ML: Orally administered lactoferrin restores humoral immune response in immunocompromised mice. Immunol Lett89 :9– 15,2003 .
   PubMed Web of Science ®Google Scholar
• Artym J, Zimecki M, Kruzel ML: Reconstitution of the cellular immune response by lactoferrin in cyclophosphamide-treated mice is correlated with renewal of T cell compartment. Immunobiology207 :197– 205,2003 .
   PubMed Web of Science ®Google Scholar
• Kuhara T, Iigo M, Itoh T, Ushida Y, Sekine K, Terada N, Okamura H, Tsuda H: Orally administered lactoferrin exerts an antimetastatic effect and enhances production of IL-18 in the intestinal epithelium. Nutr Cancer38 :192– 199,2000 .
   PubMed Web of Science ®Google Scholar
• Wang WP, Iigo M, Sato J, Sekine K, Adachi I, Tsuda H: Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin. Jpn J Cancer Res91 :1022– 1027,2000 .
   PubMedGoogle Scholar
• Varadhachary A, Wolf JS, Petrak K, O'Malley BW Jr, Spadaro M, Curcio C, Forni G, Pericle F: Oral lactoferrin inhibits growth of established tumors and potentiates conventional chemotherapy. Int J Cancer111 :398– 403,2004 .
   PubMed Web of Science ®Google Scholar
• Lee WJ, Farmer JL, Hilty M, Kim YB: The protective effects of lactoferrin feeding against endotoxin lethal shock in germfree piglets. Infect Immun66 :1421– 1426,1998 .
   PubMed Web of Science ®Google Scholar
• Broxmeyer HE, Williams DE, Hangoc G, Cooper S, Gentile P, Shen RN, Ralph P, Gillis S, Bicknell DC: The opposing actions in vivo on murine myelopoiesis of purified preparations of lactoferrin and the colony stimulating factors. Blood Cells13 :31– 48,1987 .
   PubMedGoogle Scholar
• Guillen C, McInnes IB, Vaughan D, Speekenbrink AB, Brock JH: The effects of local administration of lactoferrin on inflammation in murine autoimmune and infectious arthritis. Arthritis Rheum43 :2073– 2080,2000 .
   PubMed Web of Science ®Google Scholar
• Zimecki M, Miedzybrodzki R, Szymaniec S: Oral treatment of rats with bovine lactoferrin inhibits carrageenan-induced inflammation; correlation with decreased cytokine production. Arch Immunol Ther Exp (Warsz)46 :361– 365,1998 .
   PubMedGoogle Scholar
• Griffiths CE, Cumberbatch M, Tucker SC, Dearman RJ, Andrew S, Headon DR, Kimber I: Exogenous topical lactoferrin inhibits allergen-induced Langerhans cell migration and cutaneous inflammation in humans. Br J Dermatol144 :715– 725,2001 .
   PubMed Web of Science ®Google Scholar
• Zimecki M, Dawiskiba J, Zawirska B, Krawczyk Z, Kruzel M: Bovine lactoferrin decreases histopathological changes in the liver and regulates cytokine production by splenocytes of obstructive jaundiced rats. Inflamm Res52 :305– 310,2003 .
   PubMedGoogle Scholar
• Haversen LA, Baltzer L, Dolphin G, Hanson LA, Mattsby-Baltzer I: Anti-inflammatory activities of human lactoferrin in acute dextran sulphate-induced colitis in mice. Scand J Immunol57 :2– 10,2003 .
   PubMed Web of Science ®Google Scholar
• Elrod KC, Moore WR, Abraham WM, Tanaka RD: Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep. Am J Respir Crit Care Med156 :375– 381,1997 .
   PubMed Web of Science ®Google Scholar
• Andersen JH: Technology evaluation: rh lactoferrin, Agennix. Curr Opin Mol Ther6 :344– 349,2004 .
   PubMedGoogle Scholar
• Shimizu K, Matsuzawa H, Okada K, Tazume S, Dosako S, Kawasaki Y, Hashimoto K, Koga Y: Lactoferrin-mediated protection of the host from murine cytomegalovirus infection by a T-cell-dependent augmentation of natural killer cell activity. Arch Virol141 :1875– 1889,1996 .
   PubMed Web of Science ®Google Scholar
• Shin K, Wakabayashi H, Yamauchi K, Teraguchi S, Tamura Y, Kurokawa M, Shiraki K: Effects of orally administered bovine lactoferrin and lactoperoxidase on influenza virus infection in mice. J Med Microbiol54 :717– 723,2005 .
   PubMed Web of Science ®Google Scholar
• Weng TY, Chen LC, Shyu HW, Chen SH, Wang JR, Yu CK, Lei HY, Yeh TM: Lactoferrin inhibits enterovirus 71 infection by binding to VP1 protein and host cells. Antiviral Res67 :31– 37,2005 .
   PubMed Web of Science ®Google Scholar
• Groot F, Geijtenbeek TB, Sanders RW, Baldwin CE, Sanchez-Hernandez M, Floris R, van Kooyk Y, de Jong EC, Berkhout B: Lactoferrin prevents dendritic cell-mediated human immunodeficiency virus type 1 transmission by blocking the DC-SIGN--gp120 interaction. J Virol79 :3009– 3015,2005 .
   PubMed Web of Science ®Google Scholar
• Iwasa M, Kaito M, Ikoma J, Takeo M, Imoto I, Adachi Y, Yamauchi K, Koizumi R, Teraguchi S: Lactoferrin inhibits hepatitis C virus viremia in chronic hepatitis C patients with high viral loads and HCV genotype 1b. Am J Gastroenterol97 :766– 767,2002 .
   PubMed Web of Science ®Google Scholar
• Teraguchi S, Wakabayashi H, Kuwata H, Yamauchi K, Tamura Y: Protection against infections by oral lactoferrin: evaluation in animal models. Biometals17 :231– 234,2004 .
   PubMed Web of Science ®Google Scholar
• Zimecki M, Wlaszczyk A, Wojciechowski R, Dawiskiba J, Kruzel M: Lactoferrin regulates the immune responses in post-surgical patients. Arch Immunol Ther Exp (Warsz)49 :325– 333,2001 .
   PubMed Web of Science ®Google Scholar
• Shin K, Wakabayashi H, Yamauchi K, Teraguchi S, Tamura Y, Kurokawa M, Shiraki K: Effects of orally administered bovine lactoferrin and lactoperoxidase on influenza virus infection in mice. J Med Microbiol54 :717– 723,2005 .
   PubMed Web of Science ®Google Scholar
• Rayner TE, Cowin AJ, Robertson JG, Cooter RD, Harries RC, Regester GO, Smithers GW, Goddard C, Belford DA: Mitogenic whey extract stimulates wound repair activity in vitro and promotes healing of rat incisional wounds. Am J Physiol Regul Integr Comp Physiol278 :R1651– 1660,2000 .
   Google Scholar
• Fell JM, Paintin M, Arnaud-Battandier F, Beattie RM, Hollis A, Kitching P, Donnet-Hughes A, MacDonald TT, Walker-Smith JA: Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn's disease. Aliment Pharmacol Ther14 :281– 289,2000 .
   PubMed Web of Science ®Google Scholar
• Donnet-Hughes A, Duc N, Serrant P, Vidal K, Schiffrin EJ: Bioactive molecules in milk and their role in health and disease: the role of transforming growth factor-beta. Immunol Cell Biol78 :74– 79,2000 .
   PubMed Web of Science ®Google Scholar
• Fell JM: Control of systemic and local inflammation with transforming growth factor beta containing formulas. JPEN J Parenter Enteral Nutr29(4 Suppl) :S126– 128,2005 .
   Google Scholar
• Harsha WT, Kalandarova E, McNutt P, Irwin R, Noel J: Nutritional supplementation with transforming growth factor-beta, glutamine, and short chain fatty acids minimizes methotrexate-induced injury. J Pediatr Gastroenterol Nutr42 :53– 58,2006 .
   PubMed Web of Science ®Google Scholar
• Tsai WY, Chang WH, Chen CH, Lu FJ: Enchancing effect of patented whey protein isolate (Immunocal) on cytotoxicity of an anticancer drug. Nutr Cancer38 :200– 208,2000 .
   PubMed Web of Science ®Google Scholar
• Furlong SJ, Mader JS, Hoskin DW: Lactoferricin-induced apoptosis in estrogen-nonresponsive MDA-MB-435 breast cancer cells is enhanced by C6 ceramide or tamoxifen. Oncol Rep15 :1385– 1390,2006 .
   PubMed Web of Science ®Google Scholar
• Di Mario F, Aragona G, Bo ND, Ingegnoli A, Cavestro GM, Moussa AM, Iori V, Leandro G, Pilotto A, Franze A: Use of lactoferrin for Helicobacter pylori eradication. Preliminary results. J Clin Gastroenterol36 :396– 398,2003 .
   PubMed Web of Science ®Google Scholar
• Andersen JH, Jenssen H, Gutteberg TJ: Lactoferrin and lactoferricin inhibit Herpes simplex 1 and 2 infection and exhibit synergy when combined with acyclovir. Antiviral Res58 :209– 215,2003 .
   PubMedGoogle Scholar
• Marshall K: Therapeutic applications of whey protein. Altern Med Rev9 :136– 156,2004 .
   PubMedGoogle Scholar
• Ajello M, Greco R, Giansanti F, Massucci MT, Antonini G, Valenti P: Anti-invasive activity of bovine lactoferrin towards group A Streptococci. Biochem Cell Biol80 :119– 124,2002 .
   PubMed Web of Science ®Google Scholar
• Petitclerc D, Lauzon K, Cochu A, Ster C, Diarra MS, Lacasse P: Efficacy of a lactoferrin-penicillin combination to treat {beta}-lactam-resistant Staphylococcus aureus mastitis. J Dairy Sci90 :2778– 2787,2007 .
   PubMed Web of Science ®Google Scholar
• Chimura T, Hirayama T, Nakahara M: In vitro antimicrobial activities of lactoferrin, its concomitant use with cefpodoxime proxetil and clinical effect of cefpodoxime proxetil. Jpn J Antibiot46 :482– 485,1993 .
   PubMedGoogle Scholar
• Kennedy RS, Konok GP, Bounous G, Baruchel S, Lee TD: The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I–II clinical study. Anticancer Res15 :2643– 2649,1995 .
   PubMed Web of Science ®Google Scholar
• Bounous G, Batist G, Gold P: Whey proteins in cancer prevention. Cancer Lett57 :91– 94,1991 .
   PubMed Web of Science ®Google Scholar
• Watanabe A, Okada K, Shimizu Y, Wakabayashi H, Higuchi K, Niiya K, Kuwabara Y, Yasuyama T, Ito H, Tsukishiro T, Kondoh Y, Emi N, Kohri H: Nutritional therapy of chronic hepatitis by whey protein (non-heated). J Med31 :283– 302,2000 .
   PubMedGoogle Scholar
• Hayes TG, Falchook GF, Varadhachary GR, Smith DP, Davis LD, Dhingra HM, Hayes BP, Varadhachary A: Phase I trial of oral talactoferrin alfa in refractory solid tumors. Invest New Drugs24 :233– 240,2006 .
   PubMed Web of Science ®Google Scholar
• McBride D: Talactoferrin alpha receives fast-track designation for the treatment of non-small cell lung cancer. ONS Connect22 :14 ,2007 .
   Google Scholar
• Lyons TE, Miller MS, Serena T, Sheehan P, Lavery L, Kirsner RS, Armstrong DG, Reese A, Yankee EW, Veves A: Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study. Am J Surg193 :49– 54,2007 .
   PubMed Web of Science ®Google Scholar
• Colker CM, Swain M, Lynch L, Gingerich DA: Effects of a milk-based bioactive micronutrient beverage on pain symptoms and activity of adults with osteoarthritis: a double-blind, placebo-controlled clinical evaluation. Nutrition18 :388– 392,2002 .
   PubMedGoogle Scholar
• Pins JJ, Keenan JM: Effects of whey peptides on cardiovascular disease risk factors. J Clin Hypertens (Greenwich)8 :775– 782,2006 .
   Google Scholar
• 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 Nutr44 :258– 264,2007 .
   PubMed Web of Science ®Google Scholar
• Chabance B, Marteau P, Rambaud JC, Migliore-Samour D, Boynard M, Perrotin P, Guillet R, Jolles P, Fiat AM: Casein peptide release and passage to the blood in humans during digestion of milk or yogurt. Biochimie80 :155– 165,1998 .
   PubMed Web of Science ®Google Scholar