Health - Promoting Proteins and Peptides in Colostrum and Whey
6. Novel Applications of Bioactive Peptides
In many recent studies, traditional, fermented dairy products, such as yogurt, sour milk, dahi, quark, and different types of cheese, have proven to be rich EGF (epidermal growth factor), FGF1 and FGF2
(fi broblast growth factor), IGF - I and IGF - II (insulin - like growth factor), TGF - β 1 and TGF - β 2 (trans- forming growth factor), and PDGF (platelet - derived growth factor). As described in section 2 ,
“ Occurrence and Isolation of Bioactive Whey Proteins, ” the concentrations of all known growth factors are highest in colostrum during the fi rst hours after calving and decrease substantially there- after. Chemically, growth factors are polypeptides and their molecular masses range between 6,000 and 30,000 Daltons with amino acid residues varying from 53 (EFG) to about 425 (TGF - β 2), respectively.
An important characteristic of the growth factors present in colostrum and milk is that they seem to withstand pasteurization and even UHT (ultra high temperature) heat treatment of milk (Gauthier et al.
2006a ) relatively well.
The main biological functions of milk growth factors have been reviewed recently (Gauthier et al.
2006a ; Pouliot and Gauthier 2006 ; Tripathi and Vashishtha 2006 ). In essence, EGF and BTC stimu- late the proliferation of epidermal, epithelial, and embryonic cells. Furthermore, they inhibit the secre- tion of gastric acid and promote wound healing and bone resorption. The TDF - β family plays an impor- tant role in the development of embryo, tissue repair, formation of bone and cartilage, and in regulation of the immune system. Both forms of TGF - β are known to stimulate proliferation of connective tissue cells and inhibit proliferation of lymphocytes and epithelial cells. Both forms of IGF stimulate prolif- eration of many cell types and regulate some meta- bolic functions, for example, glucose uptake and synthesis of glycogen (Pouliot and Gauthier 2006 ).
Contradictory results are reported from studies concerning the stability of growth factors in the gas- trointestinal tract. Many animal model studies have, however, shown that EGF, IGF - I, and both TGF forms can provoke various local effects on the gas- trointestinal tract and can be absorbed intact or par- tially from intestine into blood circulation. At present, there are very few human studies performed about the potential physiological effects of oral administration of bovine growth factors. Mero et al.
(2002) have demonstrated that oral administration
α - la and β - lg have proven good precursor proteins of bioactive peptides with a wide range of bioactivi- ties, such as antihypertensive, antimicrobial, anti- oxidative, anticarcinogenic, immunomodulatory, opioid, hypocholesterolemic, and other metabolic effects (Chatterton et al. 2006 ). Of particular interest are the antihypertensive peptide β - lactosin B (Ala - Leu - Pro - Met; f(142 - 145)), which has shown signifi - cant antihypertensive activity when administered orally to SHR rats (Murakami et al. 2004 ), and a tryptic peptide of β - lg (Ile - Ile - Ala - Glu - Lys; f(71 - 75)), which has exerted hypocholesterolemic activ- ity in rat model studies (Nagaoka et al. 2001 ). Also an opioid peptide, β - lactorphin (Tyr - Leu - Leu - Phe;
f(102 - 105)), has been shown to improve arterial functions in SHR rats (Sipola et al. 2002 ). β - lg - derived peptides carry much biological potential, but further in vivo studies are essential to validate the physiological effects. This view is supported by a study of Roufi k et al. (2006) , who showed that a β - lg - derived ACE - inhibitory peptide (ALPMHIR;
f[142 - 148]) was rapidly degraded upon in vitro incubation with human serum and after oral inges- tion could not be detected in sera of human subjects.
An increasing number of ingredients containing specifi c bioactive peptides derived from milk protein hydrolysates have been launched on the market within the past few years or are currently under development. Examples of these commercial ingre- dients and their applications are listed in Table 11.2 .
7. Conclusion
The global interest in developing heath - promoting functional foods provides a timely opportunity to tap the many innate bioactive milk proteins for inclusion in such formulations. Moving from science to commercial applications now seems appropriate as the fundamental biological properties and mecha- nism of action of milk proteins, bioactive peptides, and growth factors are reasonably well established.
Also, industrial or semi - industrial scale processing techniques are available for fractionation and isola- tion of such components from colostrum and milk.
Fractionation and marketing of bioactive milk sources of bioactive peptides formed during the fer-
mentation process (Chobert et al. 2005 ; FitzGerald and Murray 2006 ; Gobbetti et al. 2007 ). The occur- rence, specifi c activity, and amount of such peptides in fermented dairy products depend on many factors, including type of starters used, type of product, time of fermentation, and storage conditions (Korhonen and Pihlanto 2006 ; Ard ö et al. 2007 ; Ong et al.
2007 ). The formation of peptides can be regulated to some extent by starter cultures used, but the sta- bility of desired peptides during storage seems dif- fi cult to control (Ryh ä nen et al. 2001 ; B ü tikofer et al. 2007 ). The potential health benefi ts attributable to bioactive peptides formed in traditional dairy products warrant extensive research. A study by Ashar and Chand (2004) demonstrated that admin- istration of an Indian fermented milk, “ dahi, ” reduced blood pressure in middle - aged hypertensive male subjects. The technological optimization of release of bioactive peptides in traditional dairy products and the potential health benefi ts of these peptides deserve further research.
Recently, commercial proteolytic enzymes and starter cultures have been employed successfully for production of specifi c bioactive peptides from various milk protein fractions. Such preparations are now commercially available and are being used as ingredients in different consumer products, such as dairy and fruit - based drinks, confectionery, chewing gum, pastilles, and capsules. Bioactive peptides added into these products may possess antihyperten- sive, anticariogenic, mineral - binding, or stress - relieving properties (Korhonen and Pihlanto 2006 ).
So far, the best - studied peptide products are the fermented milk products Calpis ® and Evolus ® , which are targeted to subjects having mild hyperten- sion. The blood pressure – reducing effects of these two products have been established in many human studies (Hata et al. 1996 ; Seppo et al. 2003 ; Mizuno et al. 2004 ; Aihara et al. 2005 ; Jauhiainen et al.
2005 ). Both products contain hypotensive tripep- tides Val - Pro - Pro and Ile - Pro - Pro derived from both β - casein and κ - casein. Casein hydrolysates have been demonstrated to produce many peptides with strong bioactivities (Silva and Malcata 2005 ; L ó pez - Exp ó sito et al. 2007 ; Saito 2008 ), but also bovine
Table 11.2. Examples of commercial dairy products and ingredients based on bioactive peptides. * Brand Names Types of Products Functional Bioactive Peptides Health/Function Claims Manufacturers Calpis/ Ameal S Sour milk Val - Pro - Pro, Ile - Pro - Pro,
derived from β - casein and κ - casein
Blood pressure reduction Calpis Co., Japan
Evolus Fermented milk Val - Pro - Pro, Ile - Pro - Pro, derived from β - casein and κ - casein
Blood pressure reduction Valio Oy, Finland
BioZate Hydrolysed whey protein isolate
β - lactoglobulin fragments Blood pressure reduction Davisco, USA BioPURE - GMP Whey protein isolate κ - casein f(106 - 169)
(Glycomacropeptide)
Anticariogenic, antimicrobial, Antithrombotic,
Davisco, USA
ProDiet F200/
Lactium
Flavored milk drink, confectionery, capsules
α s1 - casein f(91 – 100) (Tyr - Leu - Gly - Tyr - Leu - Glu - Gln - Leu - Leu - Arg)
Stress symptoms relief Ingredia, France
PeptoPro Flavored drink Casein derived di - and tripeptides
Improves athletic
performance and muscle recovery after exercise
DSM Food Specialties, the Netherlands Vivinal Alpha Ingredient α - lactalbumin rich whey
protein hydrolysate
Aids relaxation and sleep Borculo Domo Ingredients (BDI), the Netherlands
Praventin Capsule Lactoferrin enriched whey
protein hydrolysate
Helps reduce acne DMV International, the Netherlands * Modifi ed from Korhonen and Pihlanto 2006 .
proteins and peptides is emerging as a new lucrative sector for the dairy industries and specialized bio - industries. Use of proteomic tools for discovery of active peptides and metabolomics for assessment of their effects in the body are likely to contribute tremendously to the development in this fi eld in coming years.
The dairy industry has already commercialized a few milk protein and peptide - based products, but it can be envisaged that in the near future more similar products will be launched on worldwide markets.
They could be targeted to infants, elderly, and immune - compromised people, as well as to main- tenance of good health status and prevention of diet - related chronic diseases. In view of the current global trend of increasing prevalence of obesity and related diseases, type 2 diabetes in particular, more experi- mental research should be focused on bioactive milk peptides that can regulate appetite and manage blood glucose balance. Other new areas where more
research with bioactive milk proteins and peptides is warranted are impairment of cognitive functions, memory - related diseases, and mood control. In this context, antioxidative and opioid properties of many milk peptides may be worth further investigation.
Also, potential to reduce oxidative stress in the body via oral administration of antioxidative peptides could be of considerable interest in view of the infl ammatory events caused by production of reac- tive oxygen species (ROS) in the living cells.
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