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Aspectos nutricionais da caseína - referências

 
1: Am J Clin Nutr. 2006 Nov;84(5):1070-9. Related Articles, Links
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Compared with casein or total milk protein, digestion of milk soluble proteins is too rapid to sustain the anabolic postprandial amino acid requirement.

Lacroix M, Bos C, Léonil J, Airinei G, Luengo C, Daré S, Benamouzig R, Fouillet H, Fauquant J, Tomé D, Gaudichon C.

UMR INRA 914, Physiology of Nutrition and Feeding Control Unit, Institut National Agronomique Paris-Grignon, Paris, France.

BACKGROUND: The in vivo quality of milk protein fractions has seldom been studied in humans. OBJECTIVE: Our objective was to compare the postprandial utilization of dietary nitrogen from 3 [(15)N]-labeled milk products: micellar caseins (MC), milk soluble protein isolate (MSPI), and total milk protein (TMP). DESIGN: The macronutrient intakes of 23 healthy volunteers were standardized for 1 wk, after which time the subjects ingested a meal containing MC (n = 8), MSPI (n = 7), or TMP (n = 8). [(15)N] was measured for an 8-h period in plasma amino acids, proteins, and urea and in urinary urea. RESULTS: The transfer of dietary nitrogen to urea occurred earlier after MSPI ingestion than after MC and TMP ingestion, and concentrations remained high for 8 h, concomitantly with higher but transient hyperaminoacidemia and a higher incorporation of dietary nitrogen into plasma amino acids. In contrast, deamination, postprandial hyperaminoacidemia, and the incorporation of dietary nitrogen into plasma amino acids were lower in the MC and TMP groups. Finally, total postprandial deamination values were 18.5 +/- 2.9%, 21.1 +/- 2.8%, and 28.2 +/- 2.9% of ingested nitrogen in the TMP, MC, and MSPI groups, respectively. CONCLUSIONS: Our results confirm the major role of kinetics in dietary nitrogen postprandial utilization and highlight the paradox of MSPI, which, despite its high Protein Digestibility Corrected Amino Acid Score, ensures a rate of amino acid delivery that is too rapid to sustain the anabolic requirement during the postprandial period. Milk proteins had the best nutritional quality, which suggested a synergistic effect between soluble proteins and caseins.

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PMID: 17093159 [PubMed - indexed for MEDLINE]

 
2: Am J Clin Nutr. 2007 Apr;85(4):1031-40. Related Articles, Links
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Consumption of fluid skim milk promotes greater muscle protein accretion after resistance exercise than does consumption of an isonitrogenous and isoenergetic soy-protein beverage.

Wilkinson SB, Tarnopolsky MA, Macdonald MJ, Macdonald JR, Armstrong D, Phillips SM.

Exercise Metabolism Research Group, Department of Kinesiology, McMaster University, Hamilton, Canada.

BACKGROUND: Resistance exercise leads to net muscle protein accretion through a synergistic interaction of exercise and feeding. Proteins from different sources may differ in their ability to support muscle protein accretion because of different patterns of postprandial hyperaminoacidemia. OBJECTIVE: We examined the effect of consuming isonitrogenous, isoenergetic, and macronutrient-matched soy or milk beverages (18 g protein, 750 kJ) on protein kinetics and net muscle protein balance after resistance exercise in healthy young men. Our hypothesis was that soy ingestion would result in larger but transient hyperaminoacidemia compared with milk and that milk would promote a greater net balance because of lower but prolonged hyperaminoacidemia. DESIGN: Arterial-venous amino acid balance and muscle fractional synthesis rates were measured in young men who consumed fluid milk or a soy-protein beverage in a crossover design after a bout of resistance exercise. RESULTS: Ingestion of both soy and milk resulted in a positive net protein balance. Analysis of area under the net balance curves indicated an overall greater net balance after milk ingestion (P < 0.05). The fractional synthesis rate in muscle was also greater after milk consumption (0.10 +/- 0.01%/h) than after soy consumption (0.07 +/- 0.01%/h; P = 0.05). CONCLUSIONS: Milk-based proteins promote muscle protein accretion to a greater extent than do soy-based proteins when consumed after resistance exercise. The consumption of either milk or soy protein with resistance training promotes muscle mass maintenance and gains, but chronic consumption of milk proteins after resistance exercise likely supports a more rapid lean mass accrual.

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PMID: 17413102 [PubMed - indexed for MEDLINE]

 
3: Am J Clin Nutr. 2004 Nov;80(5):1246-53. Related Articles, Links
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Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins.

Nilsson M, Stenberg M, Frid AH, Holst JJ, Björck IM.

Department of Applied Nutrition and Food Chemistry, Lund University, Sweden. mikael.nilsson@inl.lth.se

BACKGROUND: Milk products deviate from other carbohydrate-containing foods in that they produce high insulin responses, despite their low GI. The insulinotropic mechanism of milk has not been elucidated. OBJECTIVE: The objective was to evaluate the effect of common dietary sources of animal or vegetable proteins on concentrations of postprandial blood glucose, insulin, amino acids, and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1] in healthy subjects. DESIGN: Twelve healthy volunteers were served test meals consisting of reconstituted milk, cheese, whey, cod, and wheat gluten with equivalent amounts of lactose. An equicarbohydrate load of white-wheat bread was used as a reference meal. RESULTS: A correlation was found between postprandial insulin responses and early increments in plasma amino acids; the strongest correlations were seen for leucine, valine, lysine, and isoleucine. A correlation was also obtained between responses of insulin and GIP concentrations. Reconstituted milk powder and whey had substantially lower postprandial glucose areas under the curve (AUCs) than did the bread reference (-62% and -57%, respectively). Whey meal was accompanied by higher AUCs for insulin (90%) and GIP (54%). CONCLUSIONS: It can be concluded that food proteins differ in their capacity to stimulate insulin release, possibly by differently affecting the early release of incretin hormones and insulinotropic amino acids. Milk proteins have insulinotropic properties; the whey fraction contains the predominating insulin secretagogue.

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PMID: 15531672 [PubMed - indexed for MEDLINE]

 
4: J Nutr. 2003 Sep;133(9):2733-40. Related Articles, Links
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Increasing habitual protein intake accentuates differences in postprandial dietary nitrogen utilization between protein sources in humans.

Morens C, Bos C, Pueyo ME, Benamouzig R, Gausserès N, Luengo C, Tomé D, Gaudichon C.

Institut National de la Recherche Agronomique, Unité de Physiologie de la Nutrition et du Comportement Alimentaire, Institut National Agronomique Paris-Grignon, 75005 Paris, France.

It is appropriate to characterize the nutritional value of dietary proteins in humans through the specific study of dietary nitrogen metabolism during the postprandial period. However, the influence of the habitual protein intake on this variable has not been studied. We aimed to describe the influence of prior protein intake on the specific metabolic utilization of dietary nitrogen in humans. Healthy men and women were adapted for 7 d to two diets with a normal [NP, 1 g/(kg x d)] and high protein content [HP, 2 g/(kg x d)]. After each period, they were studied for an 8-h postmeal period after ingesting a single (15)N-labeled mixed meal (0.41 g/kg protein) containing either milk (n = 12) or soy protein (n = 8). The HP diet reduced the peak of dietary N incorporation into free serum amino acids in the soy group but had no effect in the milk group. The incorporation of dietary N into plasma protein was higher after soy than after milk protein, but habitual protein level had no effect. The postprandial retention of milk protein was reduced by the HP diet compared with the NP diet by only 5% and that of soy protein was diminished by 13% (protein source: P < 0.0001, protein level: P < 0.0001, interaction: P < 0.001). In conclusion, the efficiency of the meal N postprandial retention was lower after HP adaptation, but this decrease was much more pronounced for soy than for milk protein, indicating that increasing the habitual protein intake accentuates differences in metabolic utilization among dietary proteins.

PMID: 12949358 [PubMed - indexed for MEDLINE]
 
5: J Dairy Sci. 1998 Apr;81(4):909-17. Related Articles, Links
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The digestible amino acid composition of several milk proteins: application of a new bioassay.

Rutherfurd SM, Moughan PJ.

Monogastric Research Centre, College of Sciences, Massey University, Palmerston North, New Zealand.

The aim of the present study was to determine the composition of amino acids that were truly digestible in the ileum. Several bovine milk products and two soy protein products were tested using the newly developed enzymatically hydrolyzed casein-ultrafiltration (UF) method. This method provides a novel approach for determining endogenous flows of amino acids at the terminal ileum, which are required for correcting apparent ileal digestibility values to true digestibility values. Digestibility was determined by sampling digesta of Sprague-Dawley male rats at the end of the small intestine (ileum). Chromic oxide was used as an indigestible marker. The traditional protein-free method for determining endogenous losses of amino acids was also used for comparison with the enzymatically hydrolyzed casein-UF method. Flows of endogenous amino acids at the terminal ileum of the rat following peptide alimentation were generally higher (1.8-fold) than those determined after a protein-free diet was fed. Compared with values for true amino acid digestibility, apparent values underestimated digestibility by 2 to 30%. True amino acid digestibility was high (79 to 102%) for all of the protein sources. The digestible amounts of methionine and lysine were 2 and 1.3 times higher, respectively, in dairy proteins than in soy proteins. The enzymatically hydrolyzed casein-UF method provides a physiological estimate of endogenous amino acid flow and appeared to be an appropriate method for correcting apparent digestibility values to true digestibility values. The data for true ileal digestibility of amino acids obtained using this technique demonstrated the high quality of bovine milk proteins.

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PMID: 9594381 [PubMed - indexed for MEDLINE]

 
6: Br J Nutr. 2003 Feb;89(2):239-48. Related Articles, Links
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Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite.

Hall WL, Millward DJ, Long SJ, Morgan LM.

Centre for Nutrition and Food Safety, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH. w.hall@surrey.ac.uk

Protein, generally agreed to be the most satiating macronutrient, may differ in its effects on appetite depending on the protein source and variation in digestion and absorption. We investigated the effects of two milk protein types, casein and whey, on food intake and subjective ratings of hunger and fullness, and on postprandial metabolite and gastrointestinal hormone responses. Two studies were undertaken. The first study showed that energy intake from a buffet meal ad libitum was significantly less 90 min after a 1700 kJ liquid preload containing 48 g whey, compared with an equivalent casein preload (P<0.05). In the second study, the same whey preload led to a 28 % increase in postprandial plasma amino acid concentrations over 3 h compared with casein (incremental area under the curve (iAUC), P<0.05). Plasma cholecystokinin (CCK) was increased by 60 % (iAUC, P<0.005), glucagon-like peptide (GLP)-1 by 65 % (iAUC, P<0.05) and glucose-dependent insulinotropic polypeptide by 36 % (iAUC, P<0.01) following the whey preload compared with the casein. Gastric emptying was influenced by protein type as evidenced by differing plasma paracetamol profiles with the two preloads. Greater subjective satiety followed the whey test meal (P<0.05). These results implicate post-absorptive increases in plasma amino acids together with both CCK and GLP-1 as potential mediators of the increased satiety response to whey and emphasise the importance of considering the impact of protein type on the appetite response to a mixed meal.

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PMID: 12575908 [PubMed - indexed for MEDLINE]

 
1: Curr Pharm Des. 2003;9(16):1257-75. Related Articles, Links
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Antibacterial and antiviral effects of milk proteins and derivatives thereof.

Florisa R, Recio I, Berkhout B, Visser S.

Department of Product Technology, NIZO food research, P.O. Box 20, 6710 BA Ede, The Netherlands.

Milk forms a rich source of biologically interesting components. In particular, its protein fraction is known to encompass many kinds of biological functions. In this review we focus on antibacterial and antiviral properties of milk proteins and milk protein derivatives. The latter include chemically modified proteins and enzymatically induced peptides. If such peptides are released by enzymes present within the digestive tract (e.g. trypsin or pepsin), it is likely that they play a role in the health defense system. This is especially the case when the active fragments can survive the intestinal conditions long enough to arrive at the right place to exert their beneficial function. In the first part of this paper attention is paid to the antibacterial proteins lactoferrin, lactoperoxidase, and lysozyme. Furthermore, antibacterial peptides originating from caseins and whey proteins are described. The second part reports on studies of antiviral effects of milk proteins and derivatives thereof. Special focus is directed to the antiviral action towards the human immunodeficiency virus (HIV) and the human cytomegalovirus (HCMV). Unmodified milk proteins are generally not active against these viruses. An exception is lactoferrin, which shows significant antiviral activity against both HIV and HCMV. Several other milk proteins tested showed strong antiviral effects only after chemical modification, i.e. by making them polyanionic (for anti-HIV activity) or polycationic (for anti-HCMV activity). In a number of cases, conclusions are drawn concerning possible relationships between antibacterial/antiviral activity and molecular structure of the components described.

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PMID: 12769735 [PubMed - indexed for MEDLINE]

 
2: J Exp Ther Oncol. 2007;6(2):89-106. Related Articles, Links

Milk-derived proteins and peptides of potential therapeutic and nutritive value.

Zimecki M, Kruzel ML.

Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.

Milk and colostrum are rich in proteins and peptides which play a crucial role in development of the immune system in mammalian offspring. Immunotropic properties of these compounds prompted investigators to search for their utility in prevention and therapy of various disorders in humans. The following constituents of milk are of particular interest: 1) Lactoferrin (LF)--exhibits antibacterial, antifungal, antiviral, antiparasite and antitumor activities. It is protective with regard to intestinal epithelium, promotes bone growth and accelerates recovery of the immune system function in immunocompromised animal; 2) A Proline-Rich Polypeptide (PRP) shows a variety of immunotropic functions, including promotion of T-cell maturation and inhibition'of autoimmune disorders. PRP was recently found to improve or stabilize the Instrumental Activity of Daily Living status in Alzheimer's disease patients. 3) Casein--has been protective in experimental bacteremia by eliciting myelopoiesis. Casein hydrolyzates were also protective in diabetic animals, reduced the tumor growth and diminished colicky symptoms in infants. Casein-derived peptides have been found to have antihypertensive effects. Glycomacropeptide (GMP)--a peptide derived from kappa casein, exhibits antibacterial and antithrombotic activities. 4) Alpha lactalbumin (LA)--demonstrates antiviral, antitumor and anti-stress properties. LA-enriched diets were anxiolytic, lowered blood pressure in rats, prevented diarrhea and led to a better weight gain in malnourished children. 5) Lysozyme--is effective in treatment of periodentitis and prevention of tooth decay. Milk enriched in lysozyme was used in feeding premature infants suffering from concomitant diseases. 6) Lactoperoxidase--shows antibacterial properties. In conclusion, milk-derived proteins and peptides are bio-accessible and safe for the prevention and treatment of numerous disorders in humans.

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PMID: 17407968 [PubMed - indexed for MEDLINE]

 
3: Life Sci. 2000 Oct 20;67(22):2745-52. Related Articles, Links
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First demonstration of an inhibitory activity of milk proteins against human immunodeficiency virus-1 reverse transcriptase and the effect of succinylation.

Wang H, Ye X, Ng TB.

Department of Microbiology, China Agricultural University, Beijing.

A variety of milk proteins including lactoferrin, angiogenin-1, alpha-lactalbumin, beta-lactoglobulin, lactoperoxidase, casein and the novel whey proteins lactogenin and glycolactin were tested for inhibitory activity toward human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT), alpha-glucosidase, beta-glucosidase and beta-glucuronidase. Lactoferrin exerted the most potent inhibitory action with an IC50 of about 6 microM. Lactoperoxidase, lactogenin, angiogenin-1 and glycolactin inhibited HIV-1 RT activity with decreasing potencies. Beta-lactoglobulin, alpha-lactalbumin and casein displayed little or no inhibitory effect. Succinylation with succinic anhydride augmented the inhibitory effect of glycolactin, beta-lactoglobulin, alpha-lactalbumin, casein and human lactoferrin. The inhibitory effect of the various milk proteins on the activities of alpha-glucosidase, beta-glucosidase and beta-glucuronidase was meager. Succinylation tended to increase the alpha-glucosidase-inhibitory effect of milk proteins but neither their beta-glucosidase-inhibitory nor beta-glucuronidase-inhibitory effect was affected.

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PMID: 11105990 [PubMed - indexed for MEDLINE]

 
4: Curr Pharm Des. 2003;9(16):1239-55. Related Articles, Links
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Biodefense properties of milk: the role of antimicrobial proteins and peptides.

Clare DA, Catignani GL, Swaisgood HE.

Southeast Dairy Foods Research Center, Department of Food Science, North Carolina State University, Raleigh, NC 27695-7624, USA. debra_clare@ncsu.edu

Mammary fluids, colostrum and milk, deliver nature's first host defense systems upon birth, and these essential liquids are critical for survival of the neonate. The identification and characterization of anti-infectious proteins were among the early scientific discoveries and this group of proteins has long been recognized for promoting health benefits in both newborns and adults. Among the more widely studied are the immunoglobulins, lactoperoxidase, lysozyme, and lactoferrin. Recently, it was shown that alpha--lactalbumin may also function in a protective capacity dependent upon its folding state. Some of these, especially lactoferrin, also display an immunomodulatory role in which case a totally separate cascade of host defense responses is initiated. It was noted that the mechanism of action for this cluster of sentry proteins does vary; thus, this protective strategy provides for a broad range of responsive reactions to infection. Presently, there is a major focus on the discovery of novel peptides that can be generated from existing milk proteins via proteolytic reactions. To date, this substrate list includes alpha--lactalbumin, beta-lactoglobulin, all casein fractions, and lactoferrin. Again, the immunoregulatory effects prompted as a result of the appearance of these peptides are currently being defined. Herein, we review the principal biological properties associated with each of these contributing milk components with a special emphasis on the role of biodefensive milk peptides. We envision future contributions emerging from this research field as an opportunity to develop effective new therapies to be used in treating infectious diseases and promoting health benefits in vivo.

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PMID: 12769734 [PubMed - indexed for MEDLINE]

 
5: Curr Pharm Des. 2006;12(13):1637-43. Related Articles, Links
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Emerging therapeutic potential of whey proteins and peptides.

Yalçin AS.

Department of Biochemistry, School of Medicine, Marmara University, Istanbul, Turkey. asyalcin@marmara.edu.tr

Whey is a natural by-product of cheese making process. Bovine milk has about 3.5% protein, 80% of which are caseins and the remaining 20% are whey proteins. Whey proteins contain all the essential amino acids and have the highest protein quality rating among other proteins. Advances in processing technologies have led to the industrial production of different products with varying protein contents from liquid whey. These products have different biological activities and functional properties. Also recent advances in processing technologies have expanded the commercial use of whey proteins and their products. As a result, whey proteins are used as common ingredients in various products including infant formulas, specialized enteral and clinical protein supplements, sports nutrition products, products specific to weight management and mood control. This brief review intends to focus on scientific evidence and recent findings related to the therapeutic potential of whey proteins and peptides.

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PMID: 16729875 [PubMed - indexed for MEDLINE]

 
6: Food Chem Toxicol. 1996 Jan;34(1):131-45. Related Articles, Links
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Antibacterial and immunostimulating casein-derived substances from milk: casecidin, isracidin peptides.

Lahov E, Regelson W.

Medical College of Virginia/Virginia Commonwealth University, Richmond 23298, USA.

Apart from immunoglobulin A and G antibodies and plasma cells, milk also contains antibiotic/host protective peptides that are of value not only for maintenance of its nutritional integrity but also for protection of the newborn and, possibly, protection of the lactating mother. Among the first such peptides identified with casecidin; following chymosin digestion of casein at pH 6 or 7, casecidin inhibited in vitro staphylococci, sarcina, Bacillus subtilis, Diplococcus pneumoniae and Streptococcus pyogenes. Inhibition occurred at high concentrations, in vitro, compared with commercial antibiotics, and thus interest in casecidin languished. Work with casecidin was followed by investigation of a related refined non-immunogenic product of chymosin digestion of alpha s1-casein. This product consisted of the N -terminal segment (1-23) of alpha s1-casein B, named "isracidin", and was significantly effective in vivo at concentrations that were competitive with known antibiotics, as seen in the protection of mice against lethal infection by Staphylococcus aureus strain Smith. Field trials showed that injection of isracidin into the udder gave protection against mastitis in sheep and cows. Isracidin was both therapeutic and prophylactic and responses to its therapeutic effect produced long-term immune resistance. Isracidin protected mice against Candida albicans, by stimulation of both phagocytosis and immune responses. However, like other recently described milk-derived peptides, despite its clinical value, isracidin was overlooked because of the lack of commercial interest in the 1970s and early 1980s, in host-mediated non-specific resistance as a therapeutic approach to infection. Another problem that impeded commercial interest was the isomeric variation in isracidin peptides seen on a large-scale batch production for commercial use. It is hoped that this review of previous studies of the activity of isracidin action will revive interest in milk as an antibiotic source.

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PMID: 8603791 [PubMed - indexed for MEDLINE]

 
7: Biopolymers. 1997;43(2):99-117. Related Articles, Links
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Milk protein-derived opioid receptor ligands.

Teschemacher H, Koch G, Brantl V.

Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität, Giessen, Germany.

Milk is mammalian characteristic and is of particular importance for humans: Mother's milk or its substitutes from cows' milk are absolutely essential nutriments for the neonate and cows' milk also represents a basic foodstuff for adults. However, in addition to their well-known nutritive role, milk constituents apparently are also able to carry specific information from the milk producer's to the milk receiver's organism: Thus, a number of milk protein fragments has been shown to behave like opioid receptor ligands able to address opioidergic systems in the adult's or in the neonate's organism. With respect to the proteins, which they are derived off these peptides have been named alpha-casein exorphins or casoxin D (alpha-casein), beta-casomorphins or beta-casorphin (beta-casein), casoxin or casoxin A, B, or C (k-casein), alpha-lactorphins (alpha-lactalbumin), beta-lactorphin (beta-lactoglobulin) or lactoferroxins (lactoferrin). Only casoxins and lactoferroxins display antagonistic properties; the other peptides behave like opioid receptor agonists. Most of the information available so far has been collected about beta-casomorphins. These peptides obviously can be released from beta-casein in the adult's or in the neonate's organism, where they might elicit opioid effects in the frame of a regulatory role as "food hormones". Several synthetic beta-casomorphin derivatives have been shown to be highly specific and potent mu-type opioid receptor ligands which frequently have been used as standard tools in opioid research.

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PMID: 9216246 [PubMed - indexed for MEDLINE]

 
8: Postepy Hig Med Dosw (Online). 2006;60:352-69. Related Articles, Links
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[Antitumor and chemopreventive activity of lactoferrin]

[Article in Polish]

Artym J.

Zakład Terapii Doświadczalnej Instytutu Immunologii i Terapii Doświadczalnej PAN, im. Ludwika Hirszfelda we Wrocławiu. limbiol@iitd.pan.wroc.pl

Lactoferrin, an evolutionarily old protein of the transferrin family, is among the proteins constituting the system of innate immunity; its action, however, also extends to the regulation of acquired immunity and other immunological phenomena. The actions of LF, confirmed in numerous in vitro and in vivo models, include participation in iron homeostasis, immunoregulatory properties, anti-inflammatory, anti-tumor, and analgesic actions, regulation of bone metabolism, participation in embryonic development, reproductive functions, and others. LF plays an important role in the normal development of a newborn. The anti-tumor properties of LF were discovered about a decade ago and have been confirmed in many laboratory, preclinical, and clinical studies. The immunomodulatory properties of LF play a major role in its anti-tumor actions. Such actions of LF appeared particularly effective in cancer patients with impaired immunity. The growth of tumors is facilitated by low expressions of MHC and co-stimulatory antigens on tumor cells and the induction of suppressor cells and other inhibitory products by tumors. Enhancement of an anti-tumor immunological response may, therefore, restrict tumor growth. Studies showed that LF elevates the number and increases the activity of T and B lymphocytes and NK cells, stimulates the release of a number of cytokines (IL-1, -6, -8, -18, IFN-gamma, TNF alpha), increases phagocytic activity and cytotoxicity of monocytes/macrophages, accelerates the maturation of T and B cells, and elevates the expression of several types of cellular receptors, such as CD4, zeta chain of the CD3 complex, LFA-1, CD11, ICAM-1, and selectin P. Apart from its immunomodulatory properties, LF exhibits direct anti-tumor actions, such as lytic, pro-apoptotic, anti-proliferative, anti-angiogenic, anti-oxidant activity and the chelation of iron ions. LF also possesses chemo-preventive properties, regulates the activity of phase I and II enzymes participating in the activation and detoxification of carcinogens, and regulates the composition of the intestinal microflora. In this way it prevents the generation of tumors and their development at early stages of carcinogenesis.

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PMID: 16885906 [PubMed - indexed for MEDLINE]

 
9: Biol Neonate. 1998;74(2):163-76. Related Articles, Links
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Protective function of proteins and lipids in human milk.

Hamosh M.

Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA. hamoshp@medlib.georgetown.edu

Human milk provides the infant with protection against infectious diseases. This protection is conferred through several mechanisms: specific antibody targeted protection against pathogens in the infant's environment (through milk IgA, IgG, and IgM) and broad-spectrum, nonspecific protection provided through several distinct mechanisms. These are: bactericidal effects (lactoferrin), bacteriostatic action (lactoferrin, lysozyme), lysis of microorganisms (lysozyme), antiviral effects (lactoferrin, products of milk fat digestion), antiprotozoan activity (free fatty acids produced during gastric and intestinal digestion of milk fat), and ligand action (inhibition of Helicobacter pylori adhesion to gastric mucosa by kappa-casein). In addition to these protective functions of the proteins and lipids of human milk, several enzymes present in human milk might provide protection by generating components that are bactericidal (bile salt dependent lipase, peroxidase), prevent inflammatory reactions (platelet-activating factor acetylhydrolase), or protect the integrity of milk proteins (antiproteases).

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PMID: 9691157 [PubMed - indexed for MEDLINE]

 
10: J Nutr. 2005 Jun;135(6):1438-43. Related Articles, Links
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Substitution of casein by beta-casein or of whey protein isolate by alpha-lactalbumin does not affect mineral balance in growing rats.

Van Dael P, Kastenmayer P, Clough J, Jarret AR, Barclay DV, Maire JC.

Nestlé Research Centre, Vers-chez-les-Blanc, CH-1000 Lausanne, Switzerland.

Bovine milk protein fractions that enable modification of the protein composition and amino acid profile of infant formulas to mimic those of human milk have recently become available. To determine the effects on protein quality and mineral bioavailability of replacing casein by beta-casein and of whey protein isolate by alpha-lactalbumin, 4 groups of growing rats were fed for 3 wk diets containing 10% protein as 1) casein (control); 2) beta-casein; 3) casein:whey (40:60); or 4) beta-casein:alpha-lactalbumin (40:60). Protein quality, determined as protein efficiency ratio (PER), net protein utilization (NPU), biological value (BV) and protein digestibility (PD), as well as body weight gain, were higher (P < 0.05) with consumption of the whey-adapted diets [casein:whey (40:60); beta-casein:alpha-lactalbumin (40:60)] compared with the casein diets (casein; beta-casein); however, there were no differences between the 2 casein diets or between the 2 whey-adapted diets. Apparent absorption of minerals (Ca, P, Fe, Zn) from the whey-adapted diets was higher than that from the casein diets (P < 0.05); but again, no differences were observed when casein or whey protein isolate were replaced by beta-casein or alpha-lactalbumin, respectively. Thus, substitution of casein by beta-casein or of whey protein isolate by alpha-lactalbumin does not affect protein quality or mineral bioavailability as determined in growing rats.

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PMID: 15930449 [PubMed - indexed for MEDLINE]

 
11: Biopolymers. 1997;43(2):119-28. Related Articles, Links
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Biochemical properties of regulatory peptides derived from milk proteins.

Meisel H.

Federal Dairy Research Centre, Institute for Chemistry and Physics, Kiel, Germany.

Biologically active peptides derived from milk proteins are inactive within the sequence of the precursor proteins but can be released by enzymatic proteolysis. Based on structure-activity studies, peptides with a defined bioactivity show common structural features. Moreover, many milk protein-derived peptides reveal multifunctional bioactivities. Bioactive peptide fragments originating from milk proteins should be taken into account as potential modulators of various regulatory processes in the body. Opioid peptides are opioid receptor ligands with agonistic or antagonistic activities. Angiotensin converting enzyme (ACE) inhibitory peptides can exert an antihypertensive effect. Immunomodulating casein peptides have been found to stimulate the proliferation of human lymphocytes and the phagocytic activities of macrophages. Antimicrobial peptides have been shown to kill sensitive microorganisms. Antithrombotic peptides inhibit the fibrinogen binding to a specific receptor region on the platelet surface and also inhibit aggregation of platelets. Casein phosphopeptides can form soluble organophosphate salts and may function as carriers for different minerals, especially calcium. In relation to their mode of action, bioactive peptides may reach target sites (e.g., receptors, enzymes) at the luminal side of the intestinal tract or after absorption, in peripheral organs. The physiological significance of bioactive peptides as exogenous regulatory substances is not yet fully understood. Nevertheless, several bioactive peptides derived from milk proteins have been shown to exert beneficial physiological effects. Milk-derived peptides were already produced on an industrial scale and as a consequence these peptides have been considered for application both as dietary supplements in "functional foods" and as drugs.

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PMID: 9216247 [PubMed - indexed for MEDLINE]

 
12: Altern Med Rev. 2004 Jun;9(2):136-56. Related Articles, Links
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Therapeutic applications of whey protein.

Marshall K.

Whey, a protein complex derived from milk, is being touted as a functional food with a number of health benefits. The biological components of whey, including lactoferrin, beta-lactoglobulin, alpha-lactalbumin, glycomacropeptide, and immunoglobulins, demonstrate a range of immune-enhancing properties. In addition, whey has the ability to act as an antioxidant, antihypertensive, antitumor, hypolipidemic, antiviral, antibacterial, and chelating agent. The primary mechanism by which whey is thought to exert its effects is by intracellular conversion of the amino acid cysteine to glutathione, a potent intracellular antioxidant. A number of clinical trials have successfully been performed using whey in the treatment of cancer, HIV, hepatitis B, cardiovascular disease, osteoporosis, and as an antimicrobial agent. Whey protein has also exhibited benefit in the arena of exercise performance and enhancement.

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PMID: 15253675 [PubMed - indexed for MEDLINE]

 
13: Antiviral Res. 2002 Aug;55(2):341-55. Related Articles, Links
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Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides.

Berkhout B, van Wamel JL, Beljaars L, Meijer DK, Visser S, Floris R.

Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands. b.berkhout@amc.uva.nl

In a search for natural proteins with anti-HIV activity, we screened a large set of purified proteins from bovine milk and peptide fragments thereof. Because several charged proteins and peptides are known to inhibit the process of virus entry, we selected proteins with an unusual charge composition or hydrophobicity profile. In contrast with some chemically modified (strongly negative) milk proteins, unmodified alpha(s2)-, beta- and kappa-casein, as well as several negatively and positively charged fragments thereof, did not show significant inhibition of virus replication. In fact, HIV-1 replication was elevated in the presence of beta-casein or amphiphilic fragments thereof. Bovine lactoferrin (bLF), a milk protein of 80 kDa, showed considerable inhibitory activity against HIV-1 with an IC50 of 0.4 microM. Modest inhibition was obtained with lactoferricin, a highly positively charged loop domain of bLF, indicating that other domains within the native bLF protein may also be required for inhibition. bLF blocked HIV-1 variants that use either the CXCR4 or the CCR5 coreceptor. In order to obtain further insight into the mechanism of action of this antiviral protein, we selected a bLF-resistant HIV-1 variant. The bLF-resistance phenotype is mediated by the viral envelope protein, which contains two interesting mutations that have previously been associated with an altered virus-host interaction and a modified receptor-coreceptor interaction. These results demonstrate that bLF targets the HIV-1 entry process. Copyright 2002 ElsevierScience BV.

Publication Types:


PMID: 12103434 [PubMed - indexed for MEDLINE]

 
14: Oral Dis. 2002 Jan;8(1):23-9. Related Articles, Links
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Clinical applications of antimicrobial host proteins lactoperoxidase, lysozyme and lactoferrin in xerostomia: efficacy and safety.

Tenovuo J.

Institute of Dentistry and Turku Immunology Centre, University of Turku, Finland. jorma.tenovuo@utu.fi

Innate human salivary defence proteins, lysozyme, lactoferrin and peroxidase, are known to exert a wide antimicrobial activity against a number of bacterial, viral and fungal pathogens in vitro. Therefore, these proteins, alone or in combinations, have been incorporated as preservatives in foods and pharmaceuticals as well as in oral health care products to restore salivas' own antimicrobial capacity in patients with dry mouth. These antimicrobials used in oral health care products, such as dentifrices, mouth-rinses, moisturizing gels and chewing gums, have been purified from bovine colostrum. In this review I critically evaluate the clinical efficacy and safety of this kind of preventive approach against various oral diseases and symptoms.

Publication Types:


PMID: 11936452 [PubMed - indexed for MEDLINE]

 
15: Crit Rev Food Sci Nutr. 2003;43(6):607-33. Related Articles, Links

Peptides from milk proteins and their properties.

Kilara A, Panyam D.

Arun Kilara Worldwide, 1020 Lee Road, Suite 200, Northbrook, IL 60062-3818, USA. kilara@akilara.com

This review has attempted to study the literature pertaining to peptides derived from milk proteins. Hydrolysis of milk proteins to generate peptides has been practiced for a long time and it was recognized early on in this process that the taste of hydrolyzates might hinder use of these products in food formulations. Modification of protein is necessary to form a more acceptable or utilizable product, to form a product that is less susceptible to deteriorative reactions and to form a product that is of higher nutritionall quality. Modifications may be achieved by a number of chemical and enzymatic means. This review has considered only enzymatic modification of dairy proteins. Modified proteins contain peptides and some of these peptides have been purified and their functionalities have been compared with unmodified proteins. This paper has examined the literature pertaining to improvement in functionality of enzyme-modified proteins. Improvements in solubility, emulsification, foaming and gelation were examined. There is limited information available on the sequence of the peptides necessary to improve the functional characteristics of proteins. Knowing the sequences of desirable functional peptides can lead to genetic alteration of proteins to improve functionality. Addition of synthetic peptides to intact proteins may be another way in which the functionality of proteins can be augmented. Some of the peptides in milk proteins are capable of affecting biological functions of an organism. These effects can be antimicrobial and probiotic, i.e., prevent the growth and proliferation of undesirable and pathogenic organisms, or they may promote the growth of desirable bacteria in the digestive tract of humans and animals. Peptides derived from milk protein have been shown to exert digestive and metabolic effects as well. They may also influence the immune system. These biological effects may play an important role in the development of medical foods that treat or mitigate the effects of diseases. Proteins are allergens and therefore it is possible that products derived from modification of proteins may also be allergens. The known literature about the allergenicity of peptides derived from milk proteins has been examined in this article. Last, but not the least, the taste attributes of peptides is also considered. Bitterness of hydrolyzates is a common occurrence and the origins of these bitter peptides and possible ways of mitigating this sensory defect has been discussed. Many of the peptides that enhance functionality and exert biological activity are likely to be bitter. Therefore, the bitter taste of hydrolysis products has to be dealt with in boosting the functional or nutraceutical aspects of foods containing these peptides. Analytical techniques for sequencing peptides have become more accessible and purification of peptides is commercially feasible. Computer based modeling techniques have aided the prediction of structures in these peptides. These advances, coupled with the advances in biotechnology, promise to revolutionize the future of nutraceutical and functional foods.

Publication Types:


PMID: 14669880 [PubMed - indexed for MEDLINE]

 
16: J Dairy Sci. 1993 Jan;76(1):301-10. Related Articles, Links
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Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities.

Fiat AM, Migliore-Samour D, Jollès P, Drouet L, Bal dit Sollier C, Caen J.

Laboratoire des Protéines, Centre National de la Recherche Scientifique, URA 1188, University of Paris V, France.

The present paper is devoted to the study of short peptides derived from milk proteins with physiological activities. Some of them behaved as opioids, enzyme inhibitors that convert angiotensin I, peptides that enhance calcium absorption, antiaggregating and antithrombotic peptides, and immunomodulating peptides. Some possessed several physiological properties, such as the C-terminal part of bovine alpha s1-casein. A strategic zone, containing immunostimulating and opioid peptides, could be located in cow and human beta-caseins. Few of these peptides or precursor peptides have so far been characterized in vivo in blood or brain after ingestion of milk. If, in the future, some of the active peptides cannot be characterized in vivo, they can all nevertheless be synthesized and used either as food additives or in pharmacology.

Publication Types:


PMID: 8436680 [PubMed - indexed for MEDLINE]

 
17: Curr Pharm Des. 2007;13(8):829-43. Related Articles, Links
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Technological options for the production of health-promoting proteins and peptides derived from milk and colostrum.

Korhonen H, Pihlanto A.

MTT Agrifood Research Finland, Biotechnology and Food Research, FIN-31600 Jokioinen, Finland. hannu.j.korhonen@mtt.fi.

Milk proteins are known to exert a wide range of nutritional, functional and biological activities. Apart from being a balanced source of valuable amino acids, milk proteins contribute to the consistency and sensory properties of various dairy products. Furthermore, many milk proteins possess specific biological properties which make them potential ingredients of health-promoting foods. These properties are attributed to both native protein molecules and to physiologically active peptides encrypted in the protein molecules. Considerable progress has been made over the last twenty years in technologies aimed at separation, fractionation and isolation in a purified form of many interesting proteins occurring in bovine colostrum and milk. Industrial-scale methods have been developed for native whey proteins such as immunoglobulins, lactoferrin, lactoperoxidase, alpha-lactalbumin and beta-lactoglobulin. Their large-scale manufacture and commercial exploitation is still limited although validated research data about their physiological health benefits is rapidly accumulating. Promising product concepts and novel fields of use have emerged recently, and some of these molecules have already found commercial applications. The same applies to bioactive peptides derived from different milk proteins. Active peptides can be liberated during gastrointestinal digestion or milk fermentation with proteolytic enzymes. Such peptides may exert a number of physiological effects in vivo on the gastrointestinal, cardiovascular, endocrine, immune, nervous and other body systems. However, at present the industrial-scale production of such peptides is limited by a lack of suitable technologies. On the other hand, a number of bioactive peptides have been identified in fermented dairy products, and there are already a few commercial dairy products enriched with blood pressure-reducing milk protein peptides. There is a need to develop methods to optimise the activity of bioactive peptides in food systems and to enable their optimum utilisation in the body. This review highlights existing modern technologies applicable for the isolation of bioactive native proteins and peptides derived from bovine colostrum, milk and cheese whey, and discusses aspects of their current and potential applications for human nutrition and promotion of human health.

PMID: 17430184 [PubMed - in process]
 
18: J Agric Food Chem. 2005 Oct 5;53(20):7673-80. Related Articles, Links
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Sialic acid-containing milk proteins show differential immunomodulatory activities independent of sialic acid.

Mikkelsen TL, Bakman S, Sørensen ES, Barkholt V, Frøkiaer H.

BioCentrum-DTU, Biochemistry and Nutrition, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.

The immunomodulatory activities of four sialic acid-containing milk proteins (kappa-casein, glycomacropeptide, lactoferrin, and proteose peptone-3 component) were determined, and the role of sialic acid was evaluated. Two in vitro models were used: murine splenocyte proliferation, where the effect on LPS-, Con A-, and PHA-stimulated proliferation was studied, and cytokine production in LPS-stimulated murine dendritic cells (DC). All four proteins inhibited LPS-induced splenocyte proliferation, though to different degrees, and independently of sialic acid. kappa-Casein strongly inhibited PHA-induced proliferation and had a weak inhibitory effect on Con A-induced proliferation, whereas lactoferrin stimulated Con A-induced proliferation. kappa-Casein, glycomacropeptide, and lactoferrin differentially affected cytokine production by DC: kappa-casein significantly inhibited production of TNF-alpha, IL-10, -12, -6, and -1beta, independent of sialic acid, whereas less-marked effects of glycomacropeptide and lactoferrin were seen. These findings thus point to important immunosuppressive effects of some milk proteins and indicate that they may function via different mechanisms.

Publication Types:


PMID: 16190615 [PubMed - indexed for MEDLINE]

 
19: J Dairy Res. 2003 May;70(2):189-97. Related Articles, Links

Antibacterial activity of casein-derived peptides isolated from rabbit (Oryctolagus cuniculus) milk.

Baranyi M, Thomas U, Pellegrini A.

Agricultural Biotechnology Center, Szent-Györgyi A. 4, H-2100 Gödöllo, Hungary. baranyi@abc.hu

Acid-precipitated rabbit 'whole casein' was digested by trypsin, chymotrypsin, pepsin, and clostripain to screen for possible peptides with antibacterial properties. The peptide fragments were separated by reversed-phase chromatography. The collected fractions were pooled and their antibacterial properties tested against Escherichia coli, Bacillus subtilis and Staphylococcus lentus. Three antibacterial peptide fragments derived from tryptic digestion of rabbit casein were isolated and identified. Their sequences were found as follows: HVEQLLR (residues 50-56 of beta-casein), ILPFIQSLFPFAER (residues 64-77 of beta-casein), and FHLGHLK (residues 19-25 of alpha(s1)-casein). The three peptides were synthesized and found to exert antibacterial effect against gram positive bacteria only. Proteolytic digestion of rabbit casein by chymotrypsin, pepsin and clostripain yielded several peptide fragments with antibacterial activity. Since antibiotic peptides can be released from casein during the digestion of milk proteins, our results suggest a possible antibacterial function of rabbit caseins. It is conceivable that antibacterial peptides can be generated by endopeptidases of the mammalian gastrointestinal tract possibly providing protection for new-born rabbits against aggression of micro-organisms.

Publication Types:


PMID: 12800873 [PubMed - indexed for MEDLINE]

 
20: Clin Med Res. 2006 Jun;4(2):106-13. Related Articles, Links
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Amoebicidal activity of milk, apo-lactoferrin, sIgA and lysozyme.

León-Sicairos N, López-Soto F, Reyes-López M, Godínez-Vargas D, Ordaz-Pichardo C, de la Garza M.

Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del I.P.N., Apdo. 14-740, México, D.F. 07000, México.

OBJECTIVES: To identify amoebicidal components in human milk and the effect of iron on the amoebicidal activity. DESIGN: Investigation in axenic cultures of Entamoeba histolytica trophozoites. METHODS: Amoebas were treated with 5%-20% of human, bovine and swine milk, with 10% of human milk fractions (i.e., casein, proteins except casein and fat) or with 1 mg/ml of human milk apo-lactoferrin, human secretory immunoglobulin type A (sIgA) and chicken egg-white lysozyme (i.e., purified proteins). Milk proteins were detected using immunoblot. Confocal microscopy was used to define the interaction of milk proteins (100 microM each) and amoebas. Experiments were done at least three times in triplicate, and mean and standard deviations were calculated. RESULTS: Human and bovine milk were amoebicidal showing a concentration-dependent effect. The amoebicidal effect was increased in the absence of iron. Milk protein fractions, with the exception of casein, were the components responsible for the amoebicidal activity found. Apo-lactoferrin, sIgA and lysozyme were identified in the amoebicidal milk protein fraction. Apo-lactoferrin showed the major amoebicidal effect. These proteins, either alone or in combination, showed a killing effect on the trophozoites. They bound to the amoebic membrane causing cell rounding, lipid disruption and damage. CONCLUSIONS: Milk proteins such as apo-lactoferrin, sIgA and lysozyme are able to kill Entamoeba histolytica trophozoites. This study confirms the importance of feeding breast milk to newborns.

Publication Types:


PMID: 16809402 [PubMed - indexed for MEDLINE]

 
21: Biochem Cell Biol. 2002;80(1):109-12. Related Articles, Links
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Bovine lactoferrin and lactoferricin derived from milk: production and applications.

Tomita M, Wakabayashi H, Yamauchi K, Teraguchi S, Hayasawa H.

Nutritional Science Laboratory, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, Japan.

Bovine lactoferrin is produced on an industrial scale from cheese whey or skim milk. The safety of purified lactoferrin has been confirmed from the results of a reverse mutation test using bacteria, a 13-week oral repeated-dose toxicity study in rats, and clinical studies. In order to apply active lactoferrin to various products, a process for its pasteurization was developed. Subsequently, lactoferrin has been used in a wide variety of products since it was first added to infant formula in 1986. A pepsin hydrolysate of lactoferrin is also used in infant formula. This hydrolysate contains a potent antimicrobial peptide named lactoferricin that is derived from the lactoferrin molecule by pepsin digestion. Semilarge-scale purification of lactoferricin can be performed by hydrophobic interaction chromatography. Lactoferricin also exhibits several biological actions and appears to be the functional domain of lactoferrin. Recent studies have demonstrated that oral administration of lactoferrin or lactoferricin exerts a host-protective effect in various animals and in humans. The results of these studies strongly suggest that the effects of oral lactoferrin are mediated by modulation of the immune system. Further elucidation of the clinical efficacy and mechanism of action of lactoferrin will increase the value of lactoferrin-containing products.

Publication Types:


PMID: 11908633 [PubMed - indexed for MEDLINE]

 
22: J Dairy Sci. 2000 Jun;83(6):1187-95. Related Articles, Links
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Bioactive milk peptides: a prospectus.

Clare DA, Swaisgood HE.

Department of Food Science, North Carolina State University, Raleigh 27695-7624, USA. debra_clare@ncsu.edu

Bioactive peptides have been identified within the amino acid sequences of native milk proteins. Hydrolytic reactions, such as those catalyzed by digestive enzymes, result in their release. These peptides directly influence numerous biological processes evoking behavioral, gastrointestinal, hormonal, immunological, neurological, and nutritional responses. The specific bioreactions associated with each physiological class have been well characterized. Herein, we review the scientific literature and attempt to stimulate consideration of the continued use of bioactive peptides and their expanded development as a commercial product. Several applications have already evolved. For example, phosphopeptides derived from casein fractions are currently used as both dietary and pharmaceutical supplements. Potentially, the addition of bioactive peptides to food products could improve consumer safety as a result of their antimicrobial properties. Lastly, bioactive peptides may function as health care products, providing therapeutic value for either treatment of infection or prevention of disease.

Publication Types:


PMID: 10877382 [PubMed - indexed for MEDLINE]

 
23: Crit Rev Food Sci Nutr. 2005;45(7-8):645-56. Related Articles, Links
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Milk biologically active components as nutraceuticals: review.

Séverin S, Wenshui X.

School of Food Science and Technology, Southern Yangtze University, Wuxi, 214036, China.

Milk contains components that provide critical nutritive elements, immunological protection, and biologically active substances to both neonates and adults. Milk proteins are currently the main source of a range of biologically active peptides. Concentrates of these peptides are potential health-enhancing nutraceuticals for food and pharmaceutical applications. Several bioactive peptides may be used as nutraceuticals, for example, in the treatment of diarrhea, hypertension, thrombosis, dental diseases, as well as mineral malabsorption, and immunodeficiency. Minor whey proteins, such as lactoferrin, lactoperoxidase, lysozyme, and immunoglobulins, are considered antimicrobial proteins. Milk also contains some natural bioactive substances. These include oligosaccharides, fucosylated oligosaccharides, hormones, growth factors, mucin, gangliosides, and endogenous peptides, which are present in milk at secretion. Most of the claimed physiological properties of milk bioactive components have been carried out in vitro or in animal model systems, and these hypothesized properties remain to be proven in humans. Whether these milk bioactive components will replace drugs entirely in the immediate future is still unclear, but the increasing appreciation of "drug foods" or nutraceuticals plays a complementary rather than a substitutional role to the synthetic pharmacological drugs.

Publication Types:


PMID: 16371332 [PubMed - indexed for MEDLINE]

 
24: AIDS Res Hum Retroviruses. 1996 Jun 10;12(9):769-75. Related Articles, Links

Antiviral effects of milk proteins: acylation results in polyanionic compounds with potent activity against human immunodeficiency virus types 1 and 2 in vitro.

Swart PJ, Kuipers ME, Smit C, Pauwels R, deBéthune MP, de Clercq E, Meijer DK, Huisman JG.

Department of Pharmaceutical Pharmacology and Clinical Pharmacy, University Centre for Pharmacy, Groningen, The Netherlands.

A number of native and modified milk proteins from bovine or human sources were analyzed for their inhibitory effects on human immunodeficiency virus type 1 (HIV-1) and HIV-2 in vitro in an MT4 cell test system. The proteins investigated were lactoferrin, alpha-lactalbumin, beta-lactoglobulin A, and beta-lactoglobulin B. By acylation of the amino function of the lysine residues in the proteins, using anhydrides of succinic acid or cis-aconitic acid, protein derivatives were obtained that all showed a strong antiviral activity against human immunodeficiency virus type 1 and/or 2. The in vitro IC50 values of the aconitylated proteins were in the concentration range of 0.3 to 3 nM. Succinylation or aconitylation of alpha-lactalbumin and beta-lactoglobulin A/B also produced strong anti-HIV-2 activity with IC50 values on the order 500 to 3000 nM. All compounds showed virtually no cytotoxicity at the concentration used. Peptide-scanning studies indicated that the native lactoferrin as well as the charged modified proteins strongly bind to the V3 loop of the gp120 envelope protein, with Kd values in the same concentration range as the above-mentioned IC50. Therefore, shielding of this domain, resulting in inhibition of virus-cell fusion and entry of the virus into MT4 cells, may be the likely underlying mechanism of antiviral action.

Publication Types:


PMID: 8738428 [PubMed - indexed for MEDLINE]

 
25: Curr Pharm Des. 2003;9(16):1309-23. Related Articles, Links
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Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery.

Kitts DD, Weiler K.

Food Science, Food, Nutrition and Health, Faculty of Agricultural Sciences University of B.C., Vancouver, B.C. Canada, V6T-1Z4. ddkitts@interchange.ubc.ca

There are many examples of biologically active food proteins, with physiological significance beyond the pure nutritional requirements that concern available nitrogen for normal growth and maintenance. Moreover, there are many physiologically active peptides, derived by protease activity from various food protein sources; however, relationships between structural properties and functional activities have not been completely elucidated. Many bioactive peptides have in common structural properties that include a relatively short peptide residue length (e.g. 2-9 amino acids), possessing hydrophobic amino acid residues in addition to proline, lysine or arginine groups. Bioactive peptides are also resistant to the action of digestion peptidases. Antihypertensive peptides, known as Angiotensin I converting enzyme (ACE) inhibitors have been derived from milk, corn and fish protein sources. Peptides with opioid activities are derived from wheat gluten or casein, following digestion with pepsin. Exorphins, or opioid peptides derived from food proteins such as wheat and milk (e.g. exogenous sources) have similar structure to endogenous opioid peptides, with a tyrosine residue located at the amino terminal or bioactive site. Immunomodulatory peptides derived from tryptic hydrolysates of rice and soybean proteins act to stimulate superoxide anions (reactive oxygen species-ROS), which triggers non-specific immune defense systems. Antioxidant properties that prevent peroxidation of essential fatty acids have also been shown for peptides derived from milk proteins. The addition of a Leu or Pro residue to the N-terminus of a His-His, dipeptide will enhance antioxidant activity and facilitate further synergy with non-peptide antioxidants (e.g. BHT). We also show herein, that the tryptic digests of casein yielding caseinophosphopeptides exhibits both hydrophilic and lipophilic antioxidant activity due to both metal ion sequestering and quenching of ROS. The separation and purification of bioactive peptides which will involve development of automated and continuous systems is an important field for Food chemists. Much effort has been given to develop selective column chromatography methods that can replace batch methods of salting out, or using solvent extraction to isolate and purify bioactive peptides. Advances here will enable recovery of bioactive peptides with minimal destruction thus enabling utilization by returning these active peptides to functional food or specific nutraceutical applications.

Publication Types:


PMID: 12769739 [PubMed - indexed for MEDLINE]

 
26: J AOAC Int. 2005 May-Jun;88(3):955-66. Related Articles, Links

Bioactive peptides derived from food.

Rutherfurd-Markwick KJ, Moughan PJ.

Massey University, Institute of Food, Nutrition and Human Health, Private Bag 11 222, Palmerston North, New Zealand. k.j.rutherfurd@massey.ac.nz

As interest in the ability of functional foods to impact on human health has grown over the past decade, so has the volume of knowledge detailing the beneficial roles of food-derived bioactive peptides. Bioactive peptides from both plant and animal proteins have been discovered, with to date, by far the most being isolated from milk-based products. A wide range of activities has been described, including antimicrobial and antifungal properties, blood pressure-lowering effects, cholesterol-lowering ability, antithrombotic effects, enhancement of mineral absorption, immunomodulatory effects, and localized effects on the gut. Although there is still considerable research to be performed in the area of food-derived bioactive peptides, it is clear that the generation of bioactive peptides from dietary proteins during the normal digestive process is of importance. Therefore, it will become necessary when determining dietary protein quality to consider the potential effects of latent bioactive peptides that are released during digestion of the protein.

Publication Types:


PMID: 16001873 [PubMed - indexed for MEDLINE]

 
27: Curr Med Chem. 2005;12(16):1905-19. Related Articles, Links
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Biochemical properties of peptides encrypted in bovine milk proteins.

Meisel H.

Federal Research Centre of Nutrition and Food - Location Kiel, Institute for Dairy Chemistry and Technology, D-24121 Kiel, P.O. Box 6069, Germany. meisel@bafm.de.

Milk proteins are precursors of many different biologically active peptides. These peptides are inactive within the protein sequence, requiring enzymatic proteolysis for release of the bioactive fragment from the proteins precursor. It is evident that activated peptides originating from milk proteins should be taken into account as potential modulators of various regulatory processes in the body. Activated peptides are potential modulators of various regulatory processes in the living system: immuno-modulatory peptides stimulate the activities of cells of the immune system and several cytomodulatory peptides inhibit cancer cell growth, antimicrobial peptides kill sensitive microorganisms, angiotensin-I-converting enzyme (ACE)-inhibitory peptides exert an hypotensive effect, opioid peptides are opioid receptor ligands which can modulate absorption processes in the intestinal tract, mineral binding peptides may function as carriers for different minerals, especially calcium, antithrombotic peptides inhibit fibrinogen binding to a specific receptor region on the platelet surface and inhibit aggregation of platelets. Moreover, many milk-derived peptides reveal multifunctional properties, i.e. specific peptide sequences having two or more different biological activities have been reported. Bioactive peptides can interact with target sites (e.g. receptors, enzymes) at the luminal side of the intestinal tract, or they could be absorbed and reach any potential site of action in the system to elicit physiological effects. Bioactive peptides encrypted in bovine milk proteins can be produced on an industrial-scale and are claimed to be health enhancing components for functional foods, nutraceuticals and pharmaceutical preparations that are used to reduce risk of disease or to enhance certain physiological functions.

Publication Types:


PMID: 16101509 [PubMed - indexed for MEDLINE]

 
28: Nahrung. 1995;39(1):1-20. Related Articles, Links

Bioactive peptides derived from milk proteins. Structural, physiological and analytical aspects.

Schlimme E, Meisel H.

Institut für Chemie und Physik, Bundesanstalt für Milchforschung, Kiel, Bundesrepublik Deutschland.

The primary function of dietary proteins is to supply the body adequately with indispensable amino acids and organic nitrogen. Little attention has been paid up to date to milk proteins, in particular caseins, that are currently the main source of biologically active peptides, although other animal as well as vegetable proteins are known to contain potentially bioactive sequences. Such regulatory peptides can be released by enzymatic proteolysis of caseins in vitro and in vivo and may act as potential physiological modulators of metabolism during the intestinal digestion of the diet. It has been proved that bioactive peptides derived from caseins, such as beta-casomorphins and phosphopeptides, can be released during gastrointestinal passage. It is also evident that peptides originating from food proteins should be taken into account as potential modulators of various regulatory processes in the body. The possible regulatory effects concern nutrient uptake (phosphopeptides, casomorphins), postprandial hormone secretion (casomorphins), immune defense (immunopeptides, casokinins, casomorphins) and neuroendocrine information transfer (casokinins). The advances in the research field of bioactive peptides are driven by a molecular understanding of biological processes, and analytical techniques are a critical component of this understanding. Different up-to-date methods, including peptide synthesis and immunochemistry, have been applied to the chemical characterization of bioactive peptides. Especially casein derived peptides have already found interesting applications, both as dietary supplements (phosphopeptides) and as pharmaceutical preparations (phosphopeptides, beta-casomorphins). The question of 'what kinds of bioactive peptides are beneficial and desirable as food constituents or as drugs' should be always carefully examined. However, the possibilities for the design of dietary products and 'natural' drugs look promising.

Publication Types:


PMID: 7898574 [PubMed - indexed for MEDLINE]

 
29: Nahrung. 1999 Jun;43(3):159-64. Related Articles, Links

Antihypertensive peptides derived from milk proteins.

Yamamoto N, Takano T.

Calpis Co., Ltd., R & D Center, Fuchinobe, Sagamihara-shi, Kanagawa, Japan.

This paper reviews the angiotensin I-converting enzyme inhibitory peptides originated from milk proteins. Focus was put on the peptides derived from milk casein by the action of some proteolytic enzymes and fermented products by lactic acid bacteria. Some of the angiotensin I-converting enzyme inhibitory peptides exhibit significant antihypertensive effects in spontaneously hypertensive rats. However, there were some antihypertensive peptides with low inhibitory activity of this enzyme. Key factors needed for the peptide to demonstrate the antihypertensive effects are discussed. Fermented milk, which has inhibitory activity of the enzyme, showed the reduction of blood pressure of hypertensive subjects. The possibility of the bioactive peptides for functional foods are also discussed.

Publication Types:


PMID: 10399348 [PubMed - indexed for MEDLINE]

 
30: Biochimie. 1998 Feb;80(2):155-65. Related Articles, Links
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Casein peptide release and passage to the blood in humans during digestion of milk or yogurt.

Chabance B, Marteau P, Rambaud JC, Migliore-Samour D, Boynard M, Perrotin P, Guillet R, Jollès P, Fiat AM.

CNRS-URA 1188, Université de Paris V, France.

In adult humans, after milk or yogurt ingestion, many peptides derived from alpha s1-, beta- or kappa-caseins were detected in stomach, including the kappa-caseinoglycopeptide, an inhibitor of platelet aggregation. Smaller peptides derived from casein and lactoferrin were recovered from duodenum. Two long peptides, the kappa-caseinoglycopeptide and the N-terminal peptide of alpha s1-casein, were absorbed and detected in plasma. These results support the concept that food-born peptides could have physiological activities in man.

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PMID: 9587673 [PubMed - indexed for MEDLINE]

 
31: J Nutr. 2004 Apr;134(4):980S-8S. Related Articles, Links
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Hypotensive peptides from milk proteins.

FitzGerald RJ, Murray BA, Walsh DJ.

Department of Life Sciences, University of Limerick, Limerick, Ireland. dick.fitzgerald@ul.ie

Hypertension is the major controllable risk factor associated with cardiovascular disease (CVD) events such as myocardial infarction, stroke, heart failure, and end-stage diabetes. A 5 mm Hg decrease in blood pressure has been equated with approximately 16% decrease in CVD. In the U.S. alone current annual antihypertensive drug costs are approximately dollars 15 billion. The renin-angiotensin-aldosterone system is a target for blood pressure control. Cleavage of angiotensinogen by renin produces angiotensin I which is subsequently hydrolyzed by angiotensin-I-converting enzyme (ACE) to angiotensin II (a potent vasoconstrictor). Various side effects are associated with the use of ACE inhibitory drugs in the control of blood pressure including hypotension, increased potassium levels, reduced renal function, cough, angioedema, skin rashes, and fetal abnormalities. Milk proteins, both caseins and whey proteins, are a rich source of ACE inhibitory peptides. Several studies in spontaneously hypertensive rats show that these casokinins and lactokinins can significantly reduce blood pressure. Furthermore, a limited number of human studies have associated milk protein-derived peptides with statistically significant hypotensive effects (i.e., lower systolic and diastolic pressures). The advent of effective milk protein based functional food ingredients/nutraceuticals for the prevention/control of blood pressure therefore has the potential to significantly reduce global healthcare cost.

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PMID: 15051858 [PubMed - indexed for MEDLINE]

 
32: Br J Nutr. 2000 Nov;84 Suppl 1:S3-10. Related Articles, Links

Effects of milk-derived bioactives: an overview.

Shah NP.

School of Life Science and Technology, Victoria University of Technology, Melbourne, Australia. Nagendra.shah@vu.edu.au

Milk contains various components with physiological functionality. Peptides derived from caseins and whey proteins including opioid peptides, antihypertensive peptides, casein phosphopeptides, alpha- and beta-lactorphins and albutensin have been shown to possess various bioactive properties. This review considers an overview of the bioactive components in milk proteins and whey and their physiological function.

Publication Types:


PMID: 11242440 [PubMed - indexed for MEDLINE]

 
33: J Nutr. 2007 Mar;137(3 Suppl 2):825S-9S. Related Articles, Links
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Milk peptides and blood pressure.

Jauhiainen T, Korpela R.

Valio Ltd., Research Center, Helsinki, Finland.

Epidemiological studies suggest that milk consumption and dietary intake of dairy proteins are inversely related to the risk for hypertension. Also, some intervention studies have shown a blood pressure-lowering effect of milk products and dairy proteins. Milk peptides are formed from milk proteins by enzymatic breakdown by digestive enzymes or by the proteinases formed by lactobacilli during the fermentation of milk. Several milk peptides have been shown to have antihypertensive effects in animal and in clinical studies. The most studied mechanism underlying the antihypertensive effects of milk peptides is inhibition of angiotensin-converting enzyme. Milk peptides may also have other additional mechanisms to lower blood pressure such as opioid-like activities and mineral-binding and antithrombotic properties. The future challenge is to identify the antihypertensive components in milk and their mechanisms of action and thus to find more possibilities for using these constituents and products as a dietary treatment of hypertension.

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PMID: 17311982 [PubMed - indexed for MEDLINE]

 
34: Am J Clin Nutr. 2000 Jul;72(1):5-14. Related Articles, Links
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Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders.

Playford RJ, Macdonald CE, Johnson WS.

Department of Gastroenterology, Imperial College School of Medicine, Hammersmith Hospital, London, UK. r.playford@ic.ac.uk

Colostrum is the specific first diet of mammalian neonates and is rich in immunoglobulins, antimicrobial peptides, and growth factors. In this article we review some of these constituents of human and bovine colostrum in comparison with those of mature milk. Recent studies suggest that colostral fractions, or individual peptides present in colostrum, might be useful for the treatment of a wide variety of gastrointestinal conditions, including inflammatory bowel disease, nonsteroidal antiinflammatory drug-induced gut injury, and chemotherapy-induced mucositis. We therefore discuss the therapeutic possibilities of using whole colostrum, or individual peptides present in colostrum, for the treatment of various gastrointestinal diseases and the relative merits of the 2 approaches.

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PMID: 10871554 [PubMed - indexed for MEDLINE]

 
35: J Nutr. 2004 Apr;134(4):989S-95S. Related Articles, Links
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Bioactive properties of milk proteins with particular focus on anticariogenesis.

Aimutis WR.

Food Technical Development Center, Cargill, Inc, Wayzata, MN 55391, USA. bill_aimutus@cargill.com

Beyond nutrition, there is an increasing amount of data and information to demonstrate a bioactive role for dairy components in adults including a role in prevention of dental caries. Specifically, the casein fraction and hydrolysates thereof have been the focus of researchers investigating cariogenicity prevention. Tooth enamel is a polymeric substance consisting of crystalline calcium phosphate embedded in a protein matrix. Dental caries develop by acidic demineralization (calcium and phosphorus solubilization) of tooth enamel. Demineralization occurs directly (acidic food consumption) or indirectly (by fermentation products of dental plaque odontopathogenic bacteria growing on residual food particles between teeth or adhering to the plaque). Research efforts with milk derived bioactive peptides have focused on inhibition of cariogenic, plaque-forming bacteria, inhibition of tooth enamel demineralization, and subsequent enamel remineralization. Caseinophosphopeptides (CPP) and glycomacropeptide (GMP) have been patented for use in common personal hygiene products to prevent dental caries. Research has shown CPP and GMP to be growth inhibitory to the cariogenic bacteria Streptococcus mutans and other species. Additionally, CPP forms nanoclusters with amorphous calcium phosphate (AMP) at the tooth surface to provide a reservoir of calcium and phosphate ions to maintain a state of super saturation with respect to tooth enamel. This would buffer plaque pH, and also provide ions for tooth enamel remineralization. Glycosidic structures attached to GMP are important to numerous bioactive properties of the peptide including anticariogenicity. Like CPP, GMP has shown inhibitory activity to enamel demineralization and promotes tooth enamel remineralization.

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PMID: 15051859 [PubMed - indexed for MEDLINE]

 
36: J Pediatr Gastroenterol Nutr. 1992 May;14(4):450-5. Related Articles, Links

Milk protein quality in low birth weight infants: effects of protein-fortified human milk and formulas with three different whey-to-casein ratios on growth and plasma amino acid profiles.

Priolisi A, Didato M, Gioeli R, Fazzolari-Nesci A, Räihä NC.

Department of Pediatrics, University of Palermo, Italy.

Growth rates (weight, length, and head circumference) and selected biochemical indexes of protein metabolism (serum urea, acid-base status, and plasma amino acid concentrations) were determined in low birth weight (LBW) infants appropriate for gestational age (birth weight less than 1,650 g) fed three formulas differing only in the whey-to-casein ratios: 60/40, 50/50, and 35/65. A group of infants fed exclusively human milk protein (HMP)-fortified human milk was used as a control. All diets provided similar daily protein and energy intakes, which were 3.5 g/kg and 122 kcal/kg in the human milk-fed infants and 3.3 g/kg and 121 kcal/kg in the formula-fed infants. Neither weight gain nor rate of growth in length and head circumference differed between the feeding groups and reached intrauterine or better rates in all groups. Values for serum urea and acid-base status were normal and also did not differ among the groups. At the end of the study, plasma threonine concentrations were significantly higher in all formula-fed infants than in the infants fed human milk. The highest plasma threonine concentration was found in the infants receiving the whey-predominant formula. Plasma concentrations of valine, methionine, and phenylalanine were also significantly higher in all formula-fed groups when compared with the human milk group. Plasma total essential amino acid concentrations were also significantly higher in the formula-fed infants than in the human milk fed. The results show that protein quality does not affect growth rate or biochemical indexes of metabolic tolerance in LBW infants fed adequate protein and energy intakes.(ABSTRACT TRUNCATED AT 250 WORDS)

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PMID: 1517949 [PubMed - indexed for MEDLINE]