Health Benefits of Whey Protein: A Review

Abstract

Whey, a component of milk, is co-product of cheese-making and casein manufacture in the dairy industry. Nowadays, whey is recognized as a value-added ingredient in many food products. Whey and whey components are viewed as value-added ingredients in infant formulas, sports nutrition foods and beverages, and other food products. Recognition of whey as a source of
diverse biologically active compounds with unique physiological and functional attributes provides opportunities for the food industry to develop functional foods or foods that have potential health benefits. Whey-derived bioactive components have antimicrobial and antiviral properties, and enhance immune defense and bone health, and improve antioxidative activity, and help protect against cancer and cardiovascular disease, and enhance the performance of physically active individuals, among other benefits. The present review is an attempt to cover scientific aspects of whey proteins’ health benefits and critique some of the important research findings associated with them to date.

Full text

Journal of Food Science and Engineering 2 (2012) 129-137
Health Benefits of Whey Protein: A Review
Birsen Bulut Solak1 and Nihat Akin2
1. Dairy Technology Programme, Department of Food Processing, Karapınar Aydoganlar Vocational College, Selcuk University,
Karapinar, Konya 42400, Turkey
2. Department of Food Engineering, Agriculture Faculty, Selcuk University, Campus, Konya 42031, Turkey
Received: December 19, 2011 / Published: March 20, 2012.
Abstract: Whey, a component of milk, is co-product of cheese-making and casein manufacture in the dairy industry. Nowadays,
whey is recognized as a value-added ingredient in many food products. Whey and whey components are viewed as value-added
ingredients in infant formulas, sports nutrition foods and beverages, and other food products. Recognition of whey as a source of
diverse biologically active compounds with unique physiological and functional attributes provides opportunities for the food
industry to develop functional foods or foods that have potential health benefits. Whey-derived bioactive components have
antimicrobial and antiviral properties, and enhance immune defense and bone health, and improve antioxidative activity, and help
protect against cancer and cardiovascular disease, and enhance the performance of physically active individuals, among other
benefits. The present review is an attempt to cover scientific aspects of whey proteins’ health benefits and critique some of the
important research findings associated with them to date.
Key words: Whey, protein, nutrition, health benefit.
1. Introduction
Drinking milk is a practice that dates back to the
domestication of animals in prehistoric times, and has
taken advantage of the extensive nutritional value of
that natural product. However, one major part of
milk-whey, has traditionally not been paid as much
attention as happened with source milk, probably
because it is a by-product of cheese making, viewed
for a long time as of little value. Interestingly,
Hippocrates already applauded the health properties of
whey in Ancient Greece; and during the Middle Age,
whey was considered not only as a medicine, but also
even as an aphrodisiac and a skin balm: it was in fact a
regular component of salves and potions to soothe
burns, to inspire vitality and to cure various illnesses
[1, 2]. Moreover, whey protein, an excellent protein, is
chosen by individuals of all ages who value the role of
a healthy diet in helping to maintain and improve their
Corresponding author: Birsen Bulut Solak, lecturer,
research field: dairy technology. E-mail:
birsenbirsenbulut@gmail.com.
health. Indeed, there are references to various health
benefits of whey in Italian Literature dating back to
early 17th century [3].
Now we detail at whey protein system, we can see
that whey protein, 20% of total milk protein, consists
of several different proteins, including β-lactoglobulin
(β-LG), α-lactalbumin (α-LA), the heavy-and
light-chain immunoglobulins (Igs), bovine serum
albumin (BSA), lactoferrin (LF), lactoperoxidase, and
glycomacropeptide (GMP) [4]. Whey may also
include the proteose-peptone components and
low-molecular weight products formed by the
enzymatic degradation of the caseins during the
cheesemaking process [5]. Whey protein contains all
20 amino acids and all nine essential amino acids, and
it is a rich and balanced source of the sulphur amino
acids that serve a critical role as antioxidants as
precursors to the potent intracellular antioxidant
glutathione and in one-carbon metabolism [6]. It
contains three to four times more bioavailable cysteine
than other proteins. Cysteine is important for the
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Health Benefits of Whey Protein: A Review
130
biosynthesis of glutathione, a tripeptide with
antioxidant, anticarcinogen, and immune stimulatory
properties. It also plays a key role in the regulation of
whole body protein metabolism, which results in
changes in body composition [7, 8]. Leucine is a
particularly important factor in tissue growth and
repair [9]. Leucine, isoleucine, and valine are thought
to play a role as metabolic regulators in protein and
glucose homoeostasis and lipid metabolism, and play
a role in weight control [7, 10-13].
Currently, the biological activity of some of the
minor whey proteins and peptides that can be isolated
is actively studied. Current evidence for the potential
of whey proteins and peptides to have health benefits
beyond basic nutrition, that is to act as functional
foods/food ingredients, arises from a number of
sources. Emerging research findings largely from in
vitro, experimental animals and limited human studies
suggest a number of beneficial bioactivities of whey
and whey components. Whey protein supplemention
has many proven benefits [14]. Now, this review can
helped us to describe health benefits of whey proteins
and it will focus on the most recent research advances
pertaining to the biological properties of whey
proteins to date.
2. Antimicrobial and Antiviral Activities
Milk proteins contain many biologically active
proteins. Protein and peptides, in milk, specifically
whey, show promise as antibacterial and antiviral
modifiers. Whey contains several components which
may protect against toxins, bacteria, and viruses.
These components include Igs, LF and its peptide
derivative, lactoferricin, lactoperoxidase, GMP and
sphingolipids [15, 16]. Furthermore, antimicrobial
peptides may be generated from whey protein by
proteolysis during gastrointestinal transit [17]. LF,
α-LA and β-LG have been assayed for inhibitory
activity aganist human immunodeficiency virus type-1
(HIV-1) [18]. In particular, ß-LG may be potential
agents for preventing transmission of genital
herpesvirus infections as well as the spread of HIV
[19]. LF and lactoferricin inhibit a diverse range of
microorganisms including gram-negative bacteria,
gram-positive bacteria, yeast, fungi and parasitic
protozoa [20]. It has been shown to inhibit the growth
of some harmful foodborne pathogens such as E. coli
and Listeria monocytogenes [16]. LF also shows
significant antiviral activity against human
immunodeficiency virus, human cytomegalovirus
(HCMV), herpes viruses, human papillomavirus
(HPV), alphavirus and hepatitis C, B and G viruses,
among others. In addition, LF is effective aganist
several non-enveloped viruses like rotavirus,
enterovirus, paliovirus (PV), adenovirus and feline
calicivirus (FCV) [21]. It can enhance the antibacterial
activity of lysozme [22]. The antimicrobial role of LF
is of particular interest to intestinal function and in the
prevention of gastroenteric diseases through control of
intestinal microflora. While LF exhibits bactericidal
activity aganist pathogens such as coliforms, it also
provides probiotic support for benifical
microorganisms such as Bifidobacteria and
Lactobacilli ssp. [23]. Helicobacter pylori is known as
the causative agent in the majority of duodenal ulcers.
It is believed to be responsible for 50%-60% of all
gastric carcinomas. A number of studies have reported
that daily administration of LF positively suppresses
gut colonization of Helicobacter pylori in infected
subjects [24]. Whey protein activates immune cell
and/or prevents infection. Whey protein shows
promise to help combat rotaviral diarrhea, which is a
common infection that results in the death of nearly
500,000 children annually [25]. Recent studies have
shown that whey protein (α-LA) fed infants had no
diarrhea [26]. The natural antimicrobial action of
lactoperoxidase is being used in a range of oral
healthcare products and is finding application in such
products directed toward the preventation and
treatment of xerostimia (dry mouth). The
lactoperoxidase containing products have been
clinically proven to inhibit harmful microorganisms

Health Benefits of Whey Protein: A Review
131
associated with gingivitis and oral irritation, to
promote the healing of bleeding gums and reduce
inflammation, and combat both the causes and effects
of halitosis (bad breath) [27]. In vitro, findings are
indicated that the whey-derived sphingolipids,
sphingosine and lysosphingolmyelin, have
antimicrobial activity [28]. Glutathione protects the
cells against free radical damage during exercise [29].
Also, it could potentially decrease infection in HIV
infected children. Whey protein can stimulate
glutathione synthesis. Oral whey protein
supplementation increases glutathione levels in HIV
infected children. Whey protein concentrate
supplementation can possibly decrease the occurrence
of associated co-infections [30].
Caseinophosphopeptides and GMP inhibit growth of
cariogenic bacteria. Glycomacropeptide inhibits
streptococcus mutans [31]. One study demonstrated
that the inclusion of specific immunoglobulins in a
food product may extend the shelf life of the product
while it also helping in the prevention of dental caries
and oral infections [32].
3. Immune Modulating Activity
Whey products and its components are shown to
participate in host immunity [33]. Whey contains
bioactive components that may offer protection
against infections and viruses, enhance immunity,
protect against some cancers. In particular, three whey
peptides are known to boost the immune system by
increasing production of glutathione (α-LA, β-LG and
LF). Growth factors known as IgF-I and IgF-II
promote gut health and wound healing [34]. Immune
response is the highest in dietary whey protein. A
number of whey proteins (α-LA, β-LG, LF) have been
cited for their immunomodulatory effects on the
body’s immune system. Immune respone of whey
protein (α-LA) was higher than casein, soy or whey
protein [35]. LF is secreted by neutrophils and can
stimulate the growth of various cells of the immune
defense system including lymphocytes,
macrophages/monocytes, humoral immune response,
and antibody response [36]. GMP, κ-casein f
(106-169), is a highly biologically active peptide that
has the ability to modulate immune function [37].
Whey proteins contain some immunomodulating
peptides which can be released by enzymatic digestion.
Identification and isolation of these bioactive peptides
could provide insights into the preparation of potent
immunomodulating products [38]. α-Lactorphin, α-LA
f (50-53), and β-LG f (102-105), β-lactorphin also act
as ACE (angiotensin converting enzyme) inhibitors
[39]. Enzymatic hydrolates of α-LA have the ability to
bind calcium, copper, iron, magnesium, manganese,
phosphorus and zinc [40]. LF has shown to play a
major role in iron regulation in mammals. Another
advantage to the use of iron-saturated LF observed in
the human trial was that it did not produce any of the
common side effects of iron supplements such as
stomach pain, cramps [41].
4. Anticancinogenic Properties
Cancer patients undergoing radiation or
chemotherapy often have difficulty in meeting their
daily nutritional requirements due to nausea and lack of
appetite. Whey protein is an excellent protein choice for
cancer patients as it is very easy to digest and very
gentle to the system [42, 43]. Whey proteins and
peptides, as well as the other whey components, may
protect against some cancers [33]. Diets supplemented
with lactoferrin or with β-LG enhance protection
aganist the devolopment of putative tumor precursors.
The mechanism behind the apparent anticancer activity
of dietary whey protein in these studies may be related
to their sulfur amino acid contents (cysteine,
methionine) [44]. Whey protein is more protective
against development of intestinal tumors. Dairy
proteins, particularly whey offers protection against
intestinal induced tumors when compared to other
protein sources. Diets containing whey have been
shown to reduce intestinal, mammary, and colon
cancers [45]. Total dietary whey protein was

Health Benefits of Whey Protein: A Review
132
demostrated to have a protective effect aganist the
development of colon cancer in the young rat when
compared with other common proteins, including
casein, meat and soy. Intracellular concentration of
glutathione, an anticarcinogenic tripeptide, measured in
liver, was greatest in whey protein and casein. Whey is
a source of precursors (cysteine-rich proteins) for
glutathione synthesis and it may be important in
providing protection to the host by stimulating
glutathione synthesis [46]. Whey proteins contain other
critical components with proven health benefits. Its low
molecular weight peptides are natural antioxidants
potentiators that may protect body tissues from aging
and certain cancers [47]. In a vitro study, whey protein
isolate enhanced the effectiveness of an anticancer drug
[48]. Among individual whey proteins, attention has
focused on the cancer inhibitory effect of LF and
lactoferricin. In laboratory animals given chemical
carcinogens, bovine lactoferrin has been shown to
significantly inhibit colon, esophagus, lung, and bladder
cancers when administered orally in the post-initiation
stage [49, 50]. When human prostate epithelial cells
were treated with whey protein isolate, intracellular
levels of glutathione dramatically increased [51].
Sphingomyelin and other sphingolipids suppress colon
tumor development in animal experiments [52]. A
variety of studies suggest a beneficial role for calcium
against some cancers [53]. Whey proteins combat skin
cancer. Treatment with topical α-lactalbumin-oleic acid
has a beneficial and lasting effect on skin papillomas
[54]. BSA may also display anticancer activity. Breast
cancer in human is inhibited by several commerical
BSA preparations during in vitro cell culture [55].
Mader et al. [56] also demonstrated that the nature of
both synthetic and pepsin-generated lactoferricin B is
against human leukemia and carcinoma cell lines
(Colon, breast, and ovary).
5. Cardiovascular Health
Whey proteins potentially improve cardiovascular
health. Milk peptides help lower high blood pressure
[57]. Fermented milk with whey protein concentrate
lowers triglyceride levels in the blood [58]. Also,
whey protein improves blood pressure and vascular
function in overweight and obese individuals [59].
Wang et al. [60] repoted that β-LG had the ability to
bind cholesterol. Futhermore, LF was reported to
significantly inhibit the accumulation of cellular
cholestery esters in macrophages by acting as a
scavenger in a vitro study. Hydrolyzed whey protein
isolate reduced blood pressure and cholesterol [61].
Whey peptides have been shown to inhibit the activity
of ACE. ACE converts the inactive angiotensin I
hormone into angiotensin II which constricts vascular
smooth muscle thereby, increasing blood pressure.
Inhibition of ACE lowers blood pressure. 20 g dose of
hydrolyzed whey protein isolate decreases blood
pressure and it increases white blood cell count. It also
decreases low-density lipoprotein (LDL) cholesterol
[62]. Whey protein exhibits anti-hypertensive effects.
β-lactosin B from a commercial whey product is a
new anti-hypertensive peptide [63]. They stated that
whey protein supplementation has the potential to be
used as an added component in dietary plans and in
functional foods aimed in the management of the
metabolic syndrome risk factors
6. Physical Performance
Whey and whey components offer several benefits
for individuals with physically active lifestyles
according to a review [64]. Whey protein is a rich
source of branched chain amino acids (BCAAs),
containing the highest known levels of any natural
food source. BCAAs are important for athletes since
unlike the other essential amino acids, they are
metabolized directly into muscle tissue and these are
the first ones used during periods of exercise and
resistance training. Whey protein provides the body
with BCAAs to replenish decreased levels and start
repairing and rebuilding lean muscle tissue. Essential
amino acids and whey protein are equally effective in
stimulating muscle protein synthesis in elderly

Health Benefits of Whey Protein: A Review
133
individuals [65]. These amino acids provide an energy
source during endurance exercise which allows
athletes to train more intensively for longer periods of
time [66]. Moreover, whey protein is an excellent
source of the essential amino acid, leucine. Leucine is
important for athletes as it plays a key role in
promoting muscle protein synthesis and muscle
growth. Research has shown that individuals who
exercise benefit from diets high in leucine and have
more lean muscle tissue and less body fat compared to
individuals whose diet contains lower levels of leucine.
Whey protein is easy to digest protein and is
efficiently absorbed into the body. It is often referred
to as a “fast” protein for its ability to quickly provide
nourishment to muscles [29]. Indeed, its consumption
has been shown to result in faster muscle protein
synthesis as compared to other proteins. This makes
whey protein more effective than other proteins for
repairing exercise-related muscle damage and building
bigger, stronger muscles. Its consumption results in a
higher peak amino acid concentration in the blood
than other proteins [67]. Whey proteins are rich in the
amino acids, arginine and lysine, which may increase
the release of growth hormone, a stimulator of muscle
growth. Whey protein cans creatine showing an
increase in lean muscle fiber adaptations [68]. Milk
protein is better than soy protein for greater gains in
lean mass and greater muscle hypertrophy. 20 g of
whey protein casein switches net amino acid balance
to positive after ingestion. It influences muscular
power and strength and increase intracellular
glutathione. It increases net protein gain. The rate of
protein digestion affects protein gain differently
during aging in humans. Whey protein is digested
faster than casein. Faster digestion gives rise to a
quicker amino acid flood into muscle cells. Whey
protein is the preferred protein for net protein gain
[69]. Dietary protein and resistance training affect
muscle body composition in older persons. Adequate
intake of protein combats sarcopenia. Resistance
training helps older people gain muscle, hypertrophy
muscle, and increase whole body fat-free mass.
Adequate intake of protein and resistant exercise
synergistically can reduce sarcopenia [70].
7. Weight Management
Studies show that achieving and maintaining a
healthy weight can add years to your life and help
prevent weight related complications, including
diabetes, cancer and heart disease. Diet plays a key
role in any weight management program and adding
whey protein often helps make a positive difference.
Whey protein is a good choice for diabetics who need
to carefully manage food intake. It has potential as an
added component in dietary plans and in functional
foods aimed at control of appetite and body weight
and in the management of the metabolic consequences
of excess body fat. It has potential as physiologically
functional food component for persons with obesity
and its co-morbidities (hypertension, type II diabetes,
hyper-and dislipidemia) [71]. It is the best protein for
fat loss during energy restricted diets, when combined
with exercise [72]. It improves body composition and
reduces waist circumference. The researchers found
that individuals who consumed whey protein weighed
less, had less body fat [73]. Whey protein is the best
protein for fat loss during energy restricted diets [72].
It influences on appetite and hunger controlling
hormones [74]. A high-protein diet reduces energy
intake and adiposity and that whey protein is more
effective than red meat in reducing body weight gain
and increasing insulin sensitivity [75]. In addition,
whey protein helps control blood glucose levels and
has been shown to be beneficial for weight
management, both of which are often a concern for
type-II diabetics. The meal with α-lactalbumin
preserves lipid oxidation and rapidly delivers amino
acids for use during exercise improved the efficiency
of exercise training to decrease adiposity [76].
8. Bone Health
Milk contains several components effective for

Health Benefits of Whey Protein: A Review
134
bone health. Milk basic protein promotes bone
formation and suppresses bone resorption in healthy
adult men. Milk basic protein is in the whey protein
fraction. 300 mg of milk basic protein increases serum
osteocalcin concentrations. Milk basic protein
promotes bone formation and suppresses bone
resorption [77]. The milk basic protein of whey is the
active protein that activates osteoblast. The active
component in the whey protein plays an important
role in bone formation by activating osteoblasts [78].
LF is a potent regulator of bone cell activity and
increases bone formation in vivo. It increases
osteoblast differentiation and forms new bone
formation. It also decreases bone breakdown [79]. It
has powerful anabolic, differentiating and
anti-apoptotic effects on osteoblasts, and inhibits
osteoclastogenesis. It is a potential therapeutic target
in bone disorders such as osteoporosis and possibly an
important physiological regulator of bone growth [80].
Glycomacropeptide has shown inhibitory activity to
enamel demineralization and promotes tooth enamel
remineralization [31]. Some whey components (e.g.,
proteose-peptones) may protect against tooth tissue
demineralization, and other whey components,
because of their immunostimulatory effects, may have
favorable effects on dental plaque [81].
9. Other Health Benefits
An imbalance in brain serotonin levels is a possible
factor manifesting the negative effects of chronic
stress, fatigue, and delirium [82]. α-LA, a whey
protein in cow's milk with a high content of
tryptophan (a precursor of serotonin) improves
cognitive performance (i.e. memory scanning) in
stress-vulnerable individuals. α-LA rich whey protein
increases serotonin activity. Stressed individuals were
less stressed when they fed α-LA [83]. It reduces
sleepiness and improves attention processes [84].
Infant formula based on predigested (hydrolyzed)
whey protein is little less allergenic than standard
infant formula and possibly decrease the risk that the
infant will later develop allergies [85]. Whey protein
is often the preferred choice for high protein products
recommended by physicians following surgery or
burn therapy. Whey protein contains many of the
same components found in human breast milk and for
this reason, it is a key ingredient in a wide variety of
infant formulas, including those for premature infants.
In addition, whey protein is an excellent protein
choice for the expectant mother who needs increased
amounts of protein. Whey protein concentrate protects
gastric mucosa from ethanol damage. The protective
properties are due to sulfhydyl compounds,
stimulators of glutathione synthesis [86]. Whey
protein is digested quickly and provides a quick rise in
plasma amino acids [87].
10. Conclusion
The above review summarizes the results of
research undertaken to date. In some cases, the
benefits of the active peptides were demonstrated in
human and animal trials. The health benefits of whey
protein and whey proteins have been a subject of
growing commercial interest in the context of
health-promoting functional foods. Whey components,
particulary the proteins and peptides, will incresingly
be preferred as ingredients for functional foods and
nutraceuticals as active medical agents. They built
upon the strong consumer trends for health and
wellbeing, and continuing discovery and
substantiation of the biological functionalty of whey
constituents. As a result, we are likely see major
developments by the food and healthcare sectors in the
widespread application of whey proteins and their
associated peptides as functional food ingredients,
nutraceuticals, and dietary supplements.
References
[1] F.V. Kosikowski, Whey and whey foods, in: F.V.
Kosikowski (Eds.), Cheese and Fermented Milk Foods,
Edwards Brothers, New York, 1982, pp. 446-469.
[2] A.R. Madureira, C.I. Pereira, A.M.P. Gomes, M.E.
Pintado, F. Xavier Malcata, Bovine whey
proteins–Overview on their main biological properties,
Food Research International 40 (2007) 1197-1211.

Health Benefits of Whey Protein: A Review
135
[3] J.C. Baricellus, The First Little Work Concerning the
Qualities and Use of Milk, Naples Lazarum Scoriggium,
1603.
[4] J.N. De Wit, Nutritional and functional characteristics of
whey proteins in food products, J. Dairy Sci. 81 (1998)
597-608.
[5] J.N. De Wit, Functional properties of whey proteins, in:
P.F. Fox (Ed.), Developments in Dairy Chemistry-4,
Elsevier Applied Science, New York, 1989.
[6] A.K. Shoveller, B. Stoll, R.O. Ball, D.G. Burrin,
Nutritional and functional importance of intestinal
sulphur acid metabolism, J. Nutr. 135 (2005) 1609-1612.
[7] R.L. Walzem, C.J. Dillard, J.B. German, Whey
components: Millenia of evolution create functionalities
for mammalian nutrition: What we know and what we
may be overlooking, Critical Reviews in Food Science
and Nutrition 42 (2002) 353-375.
[8] G. Bounous, F. Gervais, V. Amer, G. Batist, P. Gold, The
influence of dietary whey protein on tissue glutathione
and disease of aging, Clin. Invest. Med. 12 (1989)
343-349.
[9] J.C. Anthony, Signalling pathway involved in the
translocational control of protein synthesis in skeletal
muscle by leucine, J. Nutr. 131 (2001) 856-860.
[10] J.T. Smilowitz, C.J. Dillard, J.B. German, Milk beyond
essential nutrients: The metabolic food, Australian J.
Dairy Technol. 60 (2005) 77-83.
[11] G.W. Smithers, Whey and whey proteins-From
gutter-to-gold, Int. Dairy J. 18 (2008) 695-704.
[12] M.B. Zemel, Role of calcium and dairy products in enegy
partioning and weight management, American J. Clin.
Nutr. 79 (2004) 907-912.
[13] S.R. Kimball, L.S. Jefferson, Control of protein synthesis
by amino acid availability, Curr. Opin. Clin. Nutr. Metab.
Care 5 (2002) 63-67.
[14] B. Bulut Solak, N. Akın, Nutritional value and health
benefits of whey proteins, International Scientific
Conference on Nutraceuticals and Functional Foods,
Zilina, Slovakia, June 9th-11th, 2009, p. 18.
[15] H. Wakabayashi, N. Takakura, S. Teraguchi, Y. Tamura,
Lactoferrin feeding augments peritoneal macrophage
activities in mice intraperitoneally injected with
inactivated Candida albicans, Microbiol. Immunol. 47 (1)
(2003) 37-43.
[16] R. Floris, I. Recio, B. Berkhout, S. Visser, Antibacterial
and antiviral effects of milk proteins and derivatives
thereof, Curr. Pharm. Design 9 (2003) 1257-1275.
[17] A.S. Yalcin, Emerging therapeutic potential of whey
proteins and peptides, Curr. Pharm. Design 12 (2006)
1637-1643.
[18] D.E.W. Chatterton, G. Smithers, P. Roupas, A. Brodkorb,
Bioactivity of β lactoglobulin and
α-lactalbumin–Technological implications for processing,
Int. Dairy J. 16 (11) (2006) 1229-1240.
[19] H. Kokuba, L. Aurelian, A.R. Neurath,
3-Hydroxyphthaloyl-β-lactoglobulin: IV. Antiviral
activity in the mouse model of genital herpesvirus
infection, Antivir. Chem. Chemother. 9 (1998) 353-357.
[20] N. Takakura, H. Wakabayashi, H. Ishibashi, Oral
lactoferrin treatment of experimental oral candidiasis in
mice, Antimicrob. Agents Chemother. 47 (8) (2003)
2619-2623.
[21] Y. Pan, B. Shiell, J. Wan, M.J. Coventry, H. Roginski, A.
Lee, et al., Antiviral properties of milk proteins and
peptides, Int. Dairy J. 16 (2006) 1252-1261.
[22] R.T. Ellison, T.J. Giehl, Killing of gram-negative bacteria
by lactoferrin and lysozyme, J. Clin. Invest 88 (1991)
1080-1091.
[23] R. Yamauchi, E. Wada, D. Yamada, M. Yoshikawa, K.
Wada, Effect of β lactotensin on acute stress and fear
memory, Peptides 27 (12) (2006) 3176-3182.
[24] J. Collins, A. Ali-Ibrahim, D.T. Smoot, Antibiotic
therapy for Helicobacter pylori, Med. Clinics of North
America 90 (6) (2006) 1125-1140.
[25] F.M. Wolber, Supplemental whey protein concentrate
reduces rotavirus-induced disease symptoms in suckling
mice, J. Nutr. 135 (2005) 1470-1474.
[26] W.M. Bruck, S.L. Kelleher, G.R. Gibson, K.E. Nielsen,
D.E.W. Chatterton, B. Lönnerdal, rRNA probes used to
quantify the effects of glycomacropeptide and alpha
lactalbumin supplementation on the predominant groups
of intestinal bacteria of infant rhesus monkeys challenged
with enteropathogenic Escherichia coli, J. Pediatr.
Gastroenterol. Nutr. 37 (3) (2003) 273-280.
[27] J. Tnevuo, Clinical application of antimicrobial host proteins
lactoperoxidase, lysozyme and lactoferrin in xerostomia,
efficacy and safety, Oral Diseases 8 (2002) 23-29.
[28] R.C. Sprong, M.F. Hulstein, R. Van Der Meer,
Bactericidal activities of milk lipids, Antimicrob. Agents
Chemother. 45 (4) (2001) 1298-1301.
[29] N. Middleton, P. Jelen, G. Bell, Whole blood and
mononuclear cell glutathione response to dietary whey
protein supplementation in sedentary and trained male
human subjects, Int. J. Food Sci. Nutr. 55 (2) (2004)
131-141.
[30] Y.F. Moreno, V.C. Sgarbieri, M.N. da Silva, A.A. Toro,
M.M. Vilela, Features of whey protein concentrate
supplementation in children with rapidly progressive HIV
infection, J. Trop. Pediatr. 52 (1) (2006) 34-38.
[31] R. Aimutis William, Bioactive properties of milk proteins
with particular focus on anticariogenesis, J. Nutr. 134
(2004) 989-995.
[32] H. Wei, V. Loimaranta, J. Tenovuo, S. Rokka, E.L.
Syv¨aoja, H. Korhonen, Stability and activity of specific

Health Benefits of Whey Protein: A Review
136
antibodies against Streptococcuc mutans and
Streptococcus sobrinus in bovine milk fermented with
Lactobacillus rhamnosusstrain GG or treated at ultra high
temperature, Oral Microbo. Immunol. 17 (2002) 9-15.
[33] W.J. Harper, Biological properties of whey components:
A review, The American Dairy Products Institute,
Chicago, IL, 2004, 2001 with updates 2003.
[34] L.R. Bucci, L. Unlu, Protein and aminoacids in exercise
and sport, in: J. Driskell, I. Wolinsky (Eds.), Energy
Yielding Macronutrients and Energy Metabolism in
Sports Nutrition, CRC press, Boca Raton, FL., 2000, pp.
197-200.
[35] G. Bounous, P.A. Kongshavn, Differential effect of
dietary protein type on the B cell and T-cell immune
response in mice, J. Nutr. 115 (11) (1985) 1403-1408.
[36] H. Wakabayashi, M. Takase, M. Tomita, Lactoferricin
derived from milk protein lactoferrin, Curr. Pharm.
Design 9 (2003) 1277-1287.
[37] E.W. Li, Y. Mine, Immunoenhancing effects of bovine
glycomacropeptide and its derivatives on the proliferative
response and phagocytic activities of human
macrophagelike cells, U937, J. Agric. Food Chem. 52
(2004) 2704-2708.
[38] A. Mercier, S.F. Gauthier, I. Fliss, Immunomodulating
effects of whey proteins and their enzymatic digests, Int.
Dairy J. 14 (3) (2004) 175-183.
[39] M.M. Mullally, H. Meisel, R.J. FitzGerald, Synthetic
peptides corresponding to α-lactalbumin and
β-lactoglobulin sequences with angiotensin-I-converting
enzyme inhibitory activity, Biol. Chem. Hoppe-Seyler
377 (4) (1996) 259-260.
[40] P. Etcheverry, J.C. Wallingford, D.D. Miller, R.P. Glahn,
Calcium, zinc, and iron bioavailabilities from a
commercial human milk fortifier: A comparison study, J.
Dairy Sci. 87 (11) (2004) 3629-3637.
[41] T. Uchida, T. Oda, K. Sato, H. Kawakami, Availability of
lactoferrin as a natural solubilizer of iron for food
products, Int. Dairy J. 16 (2) (2006) 95-101.
[42] G. Bounous, P. Citation, P. Gold, The biological activity
of undenatured dietary whey proteins: Role of glutathione,
Clin. Invest. Med. 14 (4) (1991) 296-309.
[43] N. Akın, Modern Yoghurt Science and Technology,
Damla Ofset, Konya, 2006, pp. 365-405.
[44] G.H. McIntosh, P.J. Royle, R.K. Le Leu, G.O. Regester,
M.A. Johnson, R.L. Grinsted, et al., Whey proteins as
functional food ingredients, Int. Dairy J. 8 (1998) 425-434.
[45] R. Hakkak, S. Korourian, M.J. Ronis, Dietary whey
protein protects against azoxymethane-induced colon
tumors in male rats, Cancer Epidemiol. Biomarkers Prev.
10 (5) (2001) 555-558.
[46] G.H. McIntosh, G.O. Regester, R.K. Le Leu, P.J. Royal,
G.W. Smithers, Dairy protein protect against
dimethylhydrazine-induced intestinal cancers in rats, J.
Nutr. 125 (4) (1995) 809-816.
[47] G. Bounous, G. Batist, P. Gold, Whey protein concentrate
(WPC) and glutathione modulation in cancer treatment,
Anticancer Research 20 (6C) (2000) 4785-4792.
[48] W.Y. Tsai, W.H. Chang, C.H. Chen, Enchancing effect of
patented whey protein isolate (Immunocal) on
cytotoxicity of an anticancer drug, Nutr. Cancer 38 (2000)
200-208.
[49] H. Tsuda, K. Sekine, K. Fujita, Cancer preventation by
bovine lactoferrin and underlying mechanism–A review
of experimential and clinical studies, Biochemistry, Cell
Biology and Biotechnology 80 (2002) 131-136.
[50] N. Akın, Modern Dairy Technology, Damla Ofset, Konya,
2010, pp. 359-413.
[51] K.D. Kent, W.J. Harper, J.A. Bomser, Effect of whey
protein isolate on glutathione concentrations and
oxidative damage in human prostate epithelial cells,
Toxicology in vitro 17 (2003) 27-33.
[52] E.M. Schmelz, M.C. Sullards, D.L. Dillehay, Colonic cell
proliferation and aberrant crypt foci formation are
inhibited by dairy glycosphingolipids in 1,
2-dimethylhydrazine-treated CF1 mice, J. Nutr. 130
(2000) 522-527.
[53] P.W. Parodi, Cow’s milk components with anti-cancer
potential, Australian J. Dairy Technol. 56 (2001) 65-73.
[54] L. Gustafsson, I. Leijonhufvud, A. Aronsson, A.K.
Mossberg, C. Svanborg, Treatment of skin papillomas
with topical α-lactalbumin-oleic acid, New England J.
Med. 350 (26) (2004) 2663-2672.
[55] I. Laursen, P. Briand, A.E. Lykkesfeldt, Serum albumin
as a modulator on growth of the human breast cancer cell
line MCF-7, Anticancer Res. 10 (2A) (1990) 343-351.
[56] J.S. Mader, J. Salsman, D.M. Conrad, D.W. Hoskin,
Bovine lactoferricin selectively induces apoptosis in
human leukemia and carcinoma cell lines, Mol. Cancer
Ther. 4 (4) (2005) 612-624.
[57] A. McNally, Milk peptides to help lower high blood
pressure, 2008, http://www.nutaingredients.com.
[58] M. Kawase, H. Hashimoto, M. Hosoda, H. Morita, A.
Hosono, Effect of administration of fermented milk
containing whey protein concentrate to rats and healthy
men on serum lipid and blood pressure, J. Dairy Sci. 83
(2) (2000) 255-263.
[59] S. Pal1, V. Ellis, The chronic effects of whey proteins on
blood pressure, vascular function, and inflammatory
markers in overweight individuals, British J. Nutr. 105
(2011) 1512-1519.
[60] Q. Wang, J.C. Allen, H.E. Swaisgood, Binding of vitamin
D and cholesterol to β lactoglobulin, J. Dairy Sci. 80 (6)
(1997) 1054-1059.
[61] J.J. Pins, J.M. Keenan, The antihypertensive effect of a

Health Benefits of Whey Protein: A Review
137
hydrolyzed whey protein isolate supplement (BioZate®1):
A pilot study, FASEB J. 17 (5) (2003) A1110.
[62] J.J. Pins, J.M. Keenan, Antihypertensive effects of a
hydrolyzed whey protein isolate supplement (BioZate®1),
Presented at the 11th International Congress on
Cardiovascular Pharmacotherapy, Montreal, Quebec,
Canada, 2002.
[63] M. Murakami, H. Tonouchi, R. Takahashi, H. Kitazawa,
Y. Kawai, H. Negishi, et al., Structural analysis of a new
anti-hypertensive peptide (beta-lactosin B) isolate from a
commercial whey product, J. Dairy Sci. 87 (7) (2004)
1967-1974.
[64] E. Ha, M.B. Zemel, Functional properties of whey, whey
components and essential amino acids: Mechanisms
underlying health benefits for active people: A review, J.
Nutr. Biochem. 14 (5) (2003) 251-258.
[65] D. Paddon-Jones, M. Sheffield-Moore, C.S. Katsanos, X.
Zhang, R.R. Wolfe, Differential stimulation of muscle
protein synthesis in elderly humans following isocaloric
ingestion of amino acids or whey protein, Experimental
Gerontology 42 (2) (2005) 215-219.
[66] D. Layman, The role of leucine in weight loss diets and
glucose hemeostasis, J. Nutr. 133 (2003) 261-267.
[67] K.D. Tipton, T.A. Elliott, M.G. Cree, S.E. Wolf, A.P.
Sanford, R.R. Wolfe, Ingestion of casein and whey
proteins result in muscle anabolism after resistance
exercise, Med. Sci. in Sports and Exercise 36 (12) (2004)
2073-2081.
[68] P.J. Cribb, A.D. Williams, C.G. Stathis, Effects of whey
isolate, creatine and resistance training on muscle
hypertrophy, Med. Sci. in Sports and Exercise 39 (2)
(2007) 298-307.
[69] M. Dangin, C. Guillet, C. Garcia-Rodenas, P. Gachon,
The rate of digestion affects protein gain differently
during aging in humans, J. Physiol. 549 (2003) 635-644.
[70] W. Campbell, Dietary protein and resistance training on
muscle and body composition in older persons, J.
American College Nutr. 26 (6) (2007) 696-703.
[71] B.L. Luhovyy, Whey proteins in the regulation of food
intake and satiety, J. American College Nutr. 26 (6)
(2007) 704-712.
[72] R.H. Demling, L. DeSanti, Effect of a hypocaloric diet
increased protein intake and resistance training on lean
mass gains and fat mass loss in overweight police officers,
Nutr. Metab. 44 (1) (2000) 21-29.
[73] D. Baer, Whey protein decreases body weight and fat in
supplemented overweight and obese adults, US
Department of Agriculture, Beltsville Human Nutrition
Research Center, Beltsville, Maryland, 2006.
[74] W.L. Hall, D.J. Millward, S.J. Long, L.M. Morgan,
Casein and whey exert different effects on plasma amino
acid profiles, gastrointestinal hormone secretion and
appetite, British J. Nutr. 89 (2003) 239-248.
[75] D.P. Belobrajdic, G.H. McIntosh, J.A. Owens, A
high-whey-protein diet reduces body weight gain and
alters insulin sensitivity relative to red meat in wistar rats,
J. Nutr. 134 (2004) 1454-1458.
[76] J.C. Bouthegourd, S.M. Roseau, L. Makarios-Lahham, A
preexercise alpha-lactalbuminenriched whey protein meal
preserves lipid oxidation and decreases adiposity in rats,
American J. Physiol. Endocrinology Metab. 283 (2002)
565-572.
[77] Y. Toba, Y. Takada, Y. Matsuoka, Y. Morita, M. Motouri,
T. Hirai, et al., Milk basic protein promotes bone
formation and suppresses bone resorption in healthy adult
men, Biosci. Biotechnol. Biochem. Res. Commications
65 (6) (2001) 1353-1357.
[78] Y. Takada, S. Aoe, M. Kumegawa, Whey protein
stimulates the proliferation and differentiation of
osteoblastic MC3T3-E1 Cells, Biosci. Biotechnol.
Biochem. Res. Commications 223 (2) (1996) 445-449.
[79] F. Lorget, J. Clough, M. Oliveira, Lactoferrin reduces in
vitro osteoclast differentiation and resorbing activity,
Biochem. Biophys. Res. Commun. 296 (2002) 261-266.
[80] D. Naot, A. Grey, I.R. Reid, J. Cornish, Lactoferrin–A
novel bone growth factor, Clin. Med. Res. 3 (2) (2005)
93-101.
[81] I.S. Johanson, Milk and dairy products: Possible effects
on dental health, J. Nutr. 46 (2002) 119-122.
[82] R.C. Van Der Mast, D. Fekkes, Serotonin and amino
acids: Partners in delirium pathophysiology, Semin. Clin.
Neuropsychiatry 5 (2) (2000) 125-131.
[83] C.R. Markus, B. Olivier, E.H. de Haan, Whey protein
rich in alpha-lactalbumin increases the ratio of plasma
tryptophan to the sum of the other large neutral amino
acids and improves cognitive performance in
stress-vulnerable subjects, American J. Clin. Nutr. 75 (6)
(2002) 1051-1056.
[84] C.R. Markus, L.M. Jonkman, J.H. Lammers, N.E. Deutz,
M.H. Messer, N. Rigtering, Evening intake of
alpha-lactalbumin increases plasma tryptophan availability
and improves morning alertness and brain measures of
attention, American J. Clin. Nutr. 81 (2005) 1026-1033.
[85] H. Szajewska, J.Z. Mrukowicz, B. Stoinska, Extensively
and partially hydrolysed preterm formulas in the
prevention of allergic diseases in preterm infants: A
randomized, double-blind trial, Acta Paediatrica 93 (2004)
1159-65.
[86] C.F. Rosaneli, A.E. Bighetti, M.A. Antônio, J.E.
Carvalho, V.C. Sgarbieri, Efficacy of whey protein
concentrate on the inhibition of stomach ulcerative
lesions caused by ethanol ingestion, J. Med. Food 5 (4)
(2002) 221-228.
[87] Y. Boirie, M. Dangin, P. Gachon, M.P. Vasson, J.L.
Maubois, B. Beaufrere, Slow and fast dietary proteins
differently modulate postprandial protein accretion,
Proceeding of the National Academy of Sci. 94 (1997)
14930-14935.