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Obesity and type 2 diabetes mellitus (DM) have grown in prevalence around the world, and recently, related diseases have been considered epidemic. Given the high cost of treatment of obesity/DM-associated diseases, strategies such as dietary manipulation have been widely studied; among them, the whey protein diet has reached popularity because it has been suggested as a strategy for the prevention and treatment of obesity and DM in both humans and animals. Among its main actions, the following activities stand out: reduction of serum glucose in healthy individuals, impaired glucose tolerance in DM and obese patients; reduction in body weight; maintenance of muscle mass; increases in the release of anorectic hormones such as cholecystokinin, leptin, and glucagon like-peptide 1 (GLP-1); and a decrease in the orexigenic hormone ghrelin. Furthermore, studies have shown that whey protein can also lead to reductions in blood pressure, inflammation, and oxidative stress.
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R E V I E W Open Access
Dietary whey protein lessens several risk factors
for metabolic diseases: a review
Gabriela TD Sousa
1
, Fábio S Lira
2
, José C Rosa
1
, Erick P de Oliveira
3
, Lila M Oyama
4
, Ronaldo V Santos
5
and
Gustavo D Pimentel
6*
Abstract
Obesity and type 2 diabetes mellitus (DM) have grown in prevalence around the world, and recently, related
diseases have been considered epidemic. Given the high cost of treatment of obesity/DM-associated diseases,
strategies such as dietary manipulation have been widely studied; among them, the whey protein diet has reached
popularity because it has been suggested as a strategy for the prevention and treatment of obesity and DM in
both humans and animals. Among its main actions, the following activities stand out: reduction of serum glucose
in healthy individuals, impaired glucose tolerance in DM and obese patients; reduction in body weight;
maintenance of muscle mass; increases in the release of anorectic hormones such as cholecystokinin, leptin, and
glucagon like-peptide 1 (GLP-1); and a decrease in the orexigenic hormone ghrelin. Furthermore, studies have
shown that whey protein can also lead to reductions in blood pressure, inflammation, and oxidative stress.
Keywords: Whey protein, Obesity, Type 2 diabetes mellitus, Appetite, Inflammation, Hypertension.
Introduction
Excess bodyweight in humans has been increasing
worldwide. It is considered an epidemic by the World
Health Organization (WHO) [1,2]. Recently, it was esti-
mated that more than 300 million people worldwide are
obese and more than 1 billion are overweight [3].
Similar to obesity, type 2 diabetes mellitus (DM) has
been regarded as a major global epidemic of the 21
st
century [4]. In addition, obese individuals twice as likely
to develop metabolic syndrome (MS) comorbidities [5].
Obesity and DM are MS-associated diseases. Although
the pathogenesis of MS and each of its components is
complex and poorly understood, abdominal obesity and
insulin resistance are recognized as risk factors for MS.
Furthermore, patients with MS have a five-fold higher
risk of developing DM [6].
Patients with DM have an elevated response to post-
prandial triacylglycerols compared to non-diabetic sub-
jects. Additionally, postprandial triacylglycerols are also
known to be strongly associated with cardiovascular
diseases [7].
Reductions in body weight can reduce obesity-related
problems [8-10]. Accordingly, dietary manipulations may
promote increased satiety, to stimulate the anorexigenic
hormones and consequent to reduce food intake and
body weight [11]. Therefore, is extremely important to
discover strategies that maximize the effect of weight
loss and inhibit weight regain after short- and long-term
of nutritional counseling [2,12,13]. Likewise, diet supple-
mentation with milk serum protein has been suggested
as an adjunct strategy in the prevention and treatment
of obesity and MS-related diseases in humans [14,15]
and animals [16,17]. In addition, dietary milk serum pro-
teins, e.g., whey protein, have high nutritional value
because it contains all essential amino acids in higher
concentrations than vegetable protein sources [18,19].
Based on that, this review aims to discuss the main
effects of whey protein in the treatment or prevention of
obesity, DM, hypertension, oxidative stress and MS-
linked metabolic complications.
Methodology
For the preparation of this review, we performed biblio-
graphic searches in databases of the CAPES Periodic
* Correspondence: gupimentel@yahoo.com.br
6
Departamento de Clínica Médica, Universidade Estadual de Campinas
(UNICAMP), Campinas/SP, MA: 13083-970, Brazil
Full list of author information is available at the end of the article
© 2012 Souza et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
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Portal, Scielo, and Medline/Pubmed, covering articles
published between 2003 and 2012. A search of articles
was made using the key words whey protein,”“milk
serum protein,”“type 2 diabetes mellitus,”“obesity,
insulin resistance,”“inflammation,”“hypertension,
metabolic syndrome,and protein hydrolysates.
Main nutritional and functional components of whey
protein
Milk serum proteins are defined as substances that
remain soluble in milk serum [20]. These proteins are
naturally formed during the production of cheese [19,21]
and account for 20% of the all protein in milk [21-23],
such as β-lactoglobulins, α-lactalbumin, immunoglobu-
lins, lactoferrin, lactoperoxidase, glycomacropeptide,
bovine serum albumin [18,20,22,24], and other proteins
[22].
In addition, whey protein has high concentrations of
branched chain amino acids (BCAAs), such as leucine,
isoleucine, and valine, which are also related to import-
ant factors for muscle growth, build, and repair [14,25].
Milk serum proteins do not coagulate in acidic condi-
tions; they resist the action of quimosine from the stom-
ach, quickly reach the jejunum [19], are rapidly digested,
and raise plasma amino acid concentrations of [21,26].
Therefore, milk serum proteins perform several func-
tions, such as mineral absorption, improvement of pro-
tein synthesis, sensitivity to hormones, and decreased
blood glucose and lipid levels [7,15,16,21,23,27-29]. In
summary, the main nutritional and functional compo-
nents of whey protein are presented in Table 1.
Improvement risk factors for metabolic diseases
Obesity
Several types of diets are being studied to find a model
that has the quality and quantity of nutrients to promote
weight loss, reduction of body fat, maintenance of
muscle mass and satiety control [10,13,14,29,35-37].
Frestedt et al. [10] demonstrated that the supplemen-
tation with a mixture of whey protein isolate with other
peptides (2 servings/day and each serving with 10 g pro-
tein) for 54 healthy subjects for 12 weeks, in addition to
47 control subjects who consumed glucose (10 g/serv-
ing) led to weight loss in both groups, but the group
supplemented with whey protein had higher weight loss.
They also had greater reductions of body fat (6.1%) and
a higher maintenance of lean mass than the control
group who had consumed just glucose.
Pilvi et al. [13] studied mice that had diet-induced
obesity and were subsequently fed a low-calorie diet with
different types of proteins (whey protein isolate, α-lactal-
bumin, β-lactoglobulin, and lactoferrin) for 50 days, and
after this period, they returned to high fat diet. The mice
that consumed α-lactalbumin (45.9 g) had a significant
loss of fat mass during the caloric restriction period and
a reduction in visceral fat during the weight recovery
period when compared to other groups. But this is not a
conclusive explanation about the mechanisms that lead
to such results.
Another component of milk, calcium, has been exten-
sively studied with a possible anti-obesity role. But Pilvi
et al. [29] observed a significant decrease in weight gain
and body fat and a higher fat excretion in mice fed for
21 weeks with high-fat diet (60% of total calories from
fat), 18% protein (whey protein isolate), and 1.8% cal-
cium carbonate (CaCO
3
) in comparison with a similar
diet that had casein as the protein source. The authors
suggest that a possible explanation for this result is the
high levels of leucine present in the whey protein, e.g.,
the leucine may modulate insulin signaling by phospha-
tidylinositol 3 kinase (PI3K) directing the energy to
muscle synthesis and not for storage in adipose tissue.
Table 1 Main components and actions of whey protein
Components Actions
β-lactoglobulin
(4557%)
Has content higher of branched chain amino acids (~25.1%). Capture
hydrophobic molecules, participating in the reduction of intestinal
absorption of lipids.
α-lactalbumin
(1525%)
Has content higher of tryptophan (6%) of all dietary proteins. It is rich
in lysine, leucine, threonine, and cysteine. It has the ability to bind to
minerals such as Ca and Zn, positively affecting their absorption.
Immunoglobulin
(1015%)
Four classes of immunoglobulins are present in serum: IgG, IgA, IgM,
and IgE. It functions as an antioxidant protection and increases immunity.
Lactoferrin (~1%) Inhibits the production of pro-inflammatory cytokines and protects
against the development of hepatitis.
Lactoperoxidase (<1%) Important antimicrobial properties
Glicomacropeptide (1015%) It is formed from the digestion of κ-casein during coagulation of
cheese. It is high in essential amino acids that favor the absorption of
minerals.
Bovine serum albumin Good profile amino acid and function of binding to lipids.
Muro Urista et al. [30], Graf et al. [31], Gilbert et al. [32], Dougkas et al. [33], Madureira et al. [34].
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Subsequently, Pilvi et al. [38] showed that mice that con-
sumed a high-fat diet (60% of total calories from fat)
with 18% protein (whey protein isolate) and 1.8% cal-
cium carbonate for 12 weeks had not only an inhibition
in the accumulation of fat mass but also an increase in
gene expression in the visceral adipose tissue of leptin
and β3-adrenergic receptor when compared to another
group of mice that received a diet with similar fat and
protein contents, that instead used casein instead of
whey and only 0.4% calcium carbonate. Thus, the
authors suggest that the whey protein isolate may reduce
obesity via improvement of leptin sensibility.
Baer et al. [35] showed that the type of protein can in-
fluence the weight loss response. Supplementation with
56 g of whey protein (consumed twice daily) for 23 weeks
diminished body weight and fat mass when compared
with the group that consumed just carbohydrates. More-
over, waist circumference and fasting ghrelin levels were
lower in the whey protein group when compared to the
group that ingested soy protein. These results demon-
strated that through yet-unknown mechanisms, different
sources of dietary protein may differentially facilitate
weight loss and affect body composition.
In addition to the type dietary of protein, the propor-
tion of nutrients also influences energy consumption
and body composition [37]. Pichon et al. [37] observed a
reduction in body weight and adipose tissue in rats after
25 days of consuming a high-protein diet (55% of total
energy intake) compared to rats that consumed a normal
protein diet (14% of energy). In addition, the results
were more pronounced with the high protein diet con-
taining whey protein isolate enriched with β-lactoglobu-
lin compared with other protein sources, such as whole
milk and whey protein concentrate. The authors sug-
gested that these results were obtained because the pro-
teins have a greater power of satiety when compared to
the other nutrients. Moreover, β-lactoglobulin may cap-
ture hydrophobic molecules, decreasing the absorption
of fat by intestinal cells. Furthermore, a high protein diet
induces to increases in thermogenesis [20].
Furthermore, the reduction of body weight and body
fat [9] and the decrease of serum triacylglycerols levels
in obese individuals are extremely important, since these
individuals are at increased risk for cardiovascular dis-
eases [23,26]. Recently, Mortensen et al. [7] showed a
decrease in triacylglycerol levels when whey protein was
supplemented in DM patients. In addition, Pal et al. [23]
confirmed these results in both overweight and obese
post-menopausal women. This reduction was found after
consumption of 45 g of whey protein isolate together
with a high-fat meal when compared to consumption of
the equivalent amount of glucose or casein. Pal et al.
[39] also showed a decrease in triacylglycerol concentra-
tion in both overweight and obese individuals after
12 weeks of supplementation with 54 g of whey protein
compared to control group (without supplementation)
and with consumption of the same amount of glucose.
As a reduction of ~20% in serum triacylglycerols has
been shown to reduce the progression of coronary dis-
eases, these results are very important to decreasing
obesity.
Kasim-Karakas et al. [40] studied the influence of the
ingestion of whey protein in overweight and obese
women with polycystic ovary syndrome (PCOS). It has
been known that a reduction in body weight improves
the symptoms of PCOS. Accordingly, the intake of 75 g
of whey protein isolate compared to 75 g of glucose
reduced the ghrelin levels for 5 hours after consumption.
Therefore, these results also suggest that the whey pro-
tein can prolong satiety.
Recently, Pal and Ellis [41] showed in overweight and
obese individuals that supplementation of whey protein
(54 g) for 12 weeks did not significantly reduce the body
weight, BMI, waist circumference, and total body fat, but
decreases the triacylglycerol and insulin levels after
treatment.
Collectively, these studies that relationship whey pro-
tein and obesity showed improvement in insulin sensitiv-
ity and lipid profile with possible increase of energy
expenditure.
Type 2 diabetes mellitus
Although insulin is a hormone anorectic [42-45] and
suppresses ghrelin [40], it is also an anabolic hormone
and therefore is related to increases in muscle protein
synthesis [42]. Furthermore, hyperinsulinemia inhibits
hormone sensitive lipase (HSL), suppressing the release
of fatty acids from adipose tissue [7] and stimulates the
lipoprotein lipase (LPL) and fatty acid synthesis, contrib-
uting to obesity [40]. However, the increase in insulin
levels after consumption of whey protein reported in
several studies is not able to promote the increase of fat
mass, perhaps due to the high leucine contents present
in whey protein and also because its consumption over
the long-term (>12 weeks) improves insulin sensitivity
[41].
Recent studies have shown the important role of whey
protein supplementation in glycemia control, possibly
through the stimulation of incretin hormones, which in-
crease fasting and postprandial insulin release and im-
prove insulin sensitivity [41,46-48].
Pichon et al. [37] showed that a high-protein diet
raises insulin concentrations compared to a normopro-
teic diet. However, in human and rat studies in which
the protein is combined with carbohydrate, an increase
in the insulin response has been observed [14-16]. In
addition, whey protein stimulates insulin secretion, and
when compared to casein, milk serum proteins have
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increased postprandial insulinotropic effects that are
probably mediated by the rapid serum absorption of
BCAAs, the improvement in glucose homeostasis in
DM, and the possible delay or withdraw of the medicine
[46] .
Recently, Gunnarsson et al. [16] showed the effects of
acute administration of whey protein plus glucose by
nasogastric tube (enteral diet) in mice when compared
to the administration of only glucose. In this study, the
authors found an increase in insulin levels three times
greater and an insulin tolerance four times greater with
consumption of whey protein.
Petersen et al. [15] observed in healthy subjects a sig-
nificant reduction in postprandial glucose (37.5%) when
consumed in a single dose containing 50 g of carbohy-
drate plus milk serum proteins (20 g in total). This de-
crease was dose-dependent; thus, the higher the protein
intake, the greater its effect on blood glucose. The same
effect was observed by Frid et al. [46] in DM subjects
that consumed milk serum protein. In this study, the
authors found a significant increase in insulin and glu-
cose-dependent insulinotropic peptide (GIP).
Recently, Mortensen et al. [7] confirmed the
hypoglycemic effect of whey protein in individuals with
DM within eight hours of consuming a meal test that
contained 45 g of whey protein compared to three other
meals containing different protein sources, casein, glu-
ten, and codfish. Moreover, within six hours of a meal
test a reduction in triacylglycerol concentrations was
observed with the supplementation of whey compared
to three other meals that contained a different type of
protein. Interestingly, all protein meals were associated
with a high-fat diet (100 g of butter).
Lan-Pidhainy and Wolever [28] also observed a signifi-
cant hypoglycemic effect in individuals with insulin re-
sistance after the consumption of a drink containing
30 g of whey protein plus 50 g of glucose compared to
groups of individuals who consumed only 50 g glucose
or another group who consumed 50 g of glucose plus
30 g of canola oil.
Studies performed in rats [16,17] showed that supple-
mentation with whey protein possibly suppressed serum
glucose level by the inhibition of the enzyme dipeptidyl
peptidase-IV (DPP-IV), whose function is to disable the
incretin hormones, such as GLP-1 (glucagon-like peptide
1) and GIP, which are both related to glycemic control.
Gunnarsson et al. [16] suggest, in mice, that the diges-
tion of whey protein leads to the formation of di- and
tri-peptides that are a substrate for DPP-IV. Neverthe-
less, Frid et al. [46] and Mortensen et al. [7] found no
changes in blood GLP-1 levels, only decreased glucose
levels after consumption of different amounts, 36.4 g
and 45 g of whey protein in DM individuals. These find-
ings may possibly occur because, in diabetic subjects,
the secretion postprandial GLP-1 is decreased [15,49]
and the enzyme activity DDP-IV is increased [50].
In healthy individuals, an increased GLP-1 levels due
to consumption of whey protein is more palatable [51].
Recently, Veldhorst et al. [51] observed an increase in
blood insulin (91%) and GLP-1 (164%) levels after con-
sumption of a diet containing 25% of calories from pro-
tein (whey protein), 55% from carbohydrates, and 20%
from lipids compared to similar quantities of casein. In
addition, non-significant reduction of blood glucose with
the consumption of whey compared to casein was
observed.
In summary, protein is important in fetal growth and
development of the pancreas. Furthermore, adaptations
to nutritional stress may permanently alter the physi-
ology and metabolism of several organs, leading to long-
term diseases such as cardiovascular diseases, DM, and
MS [24]. Likewise, Barnett et al. [24] observed reduction
of 5565% in insulin secretion in adult life in the off-
spring of mother rats who consumed low amounts of
protein (whey protein) during pregnancy. This reduction
is related to the early development of DM in adult
humans.
Therefore, whey protein may be utilized by reduce in-
sulin resistance due the increase in secretion of GLP-1
and to reduce serum glucose and insulin levels.
Hypertension
Hypertension is commonly found in patients with DM
and may affect approximately 60% of Brazilian indivi-
duals [52].
Recently, it was discovered that diet is a major deter-
minant of blood pressure. Likewise, certain foods have a
direct role in the reduction of blood pressure or add-
itional reductions in cardiovascular mortality [41,53].
Some amino acids of the whey protein, e.g., α-lactalbu-
min and β-lactoglobulin, are precursors of peptide inhi-
bitors of angiotensin-converting enzyme (ACE) [20].
ACE is a key enzyme in the regulation of blood pressure
[41].
Pal and Ellis [41] showed the hypotensive effect that
occurs after intake of whey protein (54 g protein) and
casein (27 g protein) in either obese or overweight
normotensive individuals. However, the components of
proteins that could possibly lead to the improvement of
blood pressure were not analyzed in this study. Likewise,
Lee et al. [54] found no decrease in blood pressure in
individuals with mild hypertension who consumed a
drink containing skim milk with milk serum proteins
(125 mL) for 12 weeks. The low level of peptides (2.6 g
per 100 g of protein drink) administered together with
protein may have been responsible for the absence of an
effect on blood pressure.
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In summary, whey protein is associated with reduction
blood pressure by inhibition of ACE enzyme and pos-
sibly via lower body weight gain in individuals that
habitually consumed the aminoacids from whey protein
or BCAA than those subjects that consumption others
aminoacids, for e.g. non essential. Therefore, whey pro-
tein can in the future be considered extremely important
for the control of hypertension.
Possible mechanisms involved in reducing risk factors for
metabolic diseases
Reduction of food intake
Satiety is an important factor in the regulation of food
intake and also in the control of obesity [11,45]. Dietary
protein and specific amino acids are involved in the con-
trol of gastric and intestinal motility and in pancreatic
secretion, and are more potent in inducing satiety than
carbohydrates or fats [55].
Gut peptides that regulate the digestive process and
neuronal signaling in the central nervous system (CNS)
regulate hunger and satiety [42]. Table 2 lists several
peripheral hormones and their roles in the regulation of
food intake [57].
Milk serum proteins are more potent stimulants of
cholecystokinin (CCK) and GLP-1 than casein
[26,41,51]. Among the peptides involved with whey pro-
tein, glycomacropeptide is an effective secretagogue of
CCK [36]. CCK is a hormone secreted by I cells of the
small intestine that has as one of its functions to modu-
late satiety [59]. However, Burton-Freeman [36] did not
observe the effect of dietary whey protein on the
increase of postprandial CCK levels in healthy subjects.
Therefore, we may to infer that probably a dose of whey
was insufficient to stimulate the CCK.
Pal and Ellis [41] observed a significant decrease in
glucose, appetite, and food intake, and an increase in
serum insulin levels after the consumption of a drink
containing 50 g of whey protein when compared to the
consumption of a similar amount of protein tuna, tur-
key, or egg albumin. This study suggests a potential
application of these foods in appetite control in both
overweight and obese individuals.
Furthermore, other amino acids not described in this
review are also associated with satiety, such as tryptophan,
which is a precursor of serotonin and an important modu-
lator of appetite [51].
Although the gut hormones are known by increase of
anorexigenic hormones, also was observed that the leu-
cine when injected directly in the central nervous system
reduces the food intake and body weight [60]. Further-
more, Ropelle et al. [61] found that both leucine intra-
cerebroventricular injection or high-protein diet
decrease AMPK and increase mTOR phosphorylation in
the CNS inhibiting the neuropeptide Y and stimulating
the pro-opiomelanocortin expression, leading to reduc-
tion of food intake.
In summary, these findings suggesting that the aminoa-
cids from whey protein may reduce the food intake via in-
crease of gut hormones (CCK and GLP-1), and reduction
of neuropeptide orexigenic (NPY) and increase of neuro-
peptide anorexigenic (POMC) in the hypothalamus.
Anti-inflammatory actions
Adipose tissue is an endocrine organ that releases hor-
mones, cytokines, and others substances that tend to im-
pair insulin sensitivity [55]. Obese individuals have
increased secretion of adipocytokines by adipose tissue
and macrophages [20].
Recently, Pal & Ellis [41] observed in overweight and
obese subjects that the supplementation of whey protein
(54 g) for 12 weeks did not change the pro-inflammatory
markers (IL-6, C-reactive protein-CRP, and TNF-α).
However, in D-galactosamine-induced hepatitis and liver
fibrosis in rats, the consumption of whey protein
strongly reduced the plasma levels of pro-inflammatory
cytokines (IL-1 beta: 59% and IL-6: 29%) compared to
the consumption of the same amount of casein [62].
Collectively, reduction of pro-inflammatory cytokines
may be associated with reduction of body weight gain
after consumption of whey protein and it aminoacids.
Anti-oxidative stress actions
Oxidative stress has been associated with MS, which is a
disease recognized by inflammatory effects that are
linked with the activation of reactive oxygen species
(ROS) [63-65]. Nowadays, indicators that are more
Table 2 Characteristics and functions of hormones
related to appetite regulation
Hormones Production and effects
CCK Produced: duodenum
Effect: reduces appetite
GLP-1 Produced: mainly in distal intestine (L cells)
Effect: reduces appetite
Ghrelin Produced: stomach
Effect: stimulates appetite
GIP Produced: K cells of the duodenum
Effect: reduces appetite and potentiate insulin release
Leptin Produced: mainly in adipose tissue
Effect: suppress appetite
Uroguanylin [56] Produced: intestinal epithelial cells
Effect: reduces appetite
CCK: cholecystokinin, GLP-1: glucagon-like peptide 1, GIP: glucose-dependent
insulinotropic peptide. Adapted: Pimentel & Zemdegs, 2010 [57] and Pimentel
et al. [58].
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typically used in the evaluation of ROS are the endogen-
ous antioxidant enzymes such as glutathione peroxidase,
catalase, and superoxide dismutase, and other compo-
nents such as malondialdehyde (MDA) and thiobarbitu-
ric acid reactive substances (TBARS) [63-66]. Recently,
the administration of 100 mg/kg of body weight of whey
protein in streptozotocin-induced diabetic rats was
found to decrease several oxidative stress indicators,
such as MDA, nitric oxide, and ROS concentrations; as
well as reduction of pro-inflammatory cytokines (IL-1β,
TNF-α, IL-6 and IL-4) and increase glutathione levels
[67]. Another study observed that rats fed high-carbohy-
drate, fat-free diets to induce fatty livers (nonalcoholic
fatty liver model) plus orally administered whey protein
(0.15 g/d/rat) for 28 days reduced MDA and increased
glutathione levels [68].
Haraguchi et al. [19] found a protective effect against
oxidative stress, mainly in the liver, and a beneficial ef-
fect on renal function in rats supplemented with whey
protein plus a hypercholesterolemic diet, but they did
not observe a reduction in serum cholesterol levels.
In human studies, beneficial effects in the reduction of
oxidative stress after treatment with whey protein [69-
71]. Likewise, supplementation with 20 g/d of whey pro-
tein isolate for 12 weeks in subjects with nonalcoholic
steatohepatitis was found to increase the glutathione and
total antioxidant capacities [70]. In healthy individuals,
45 g/day of whey protein supplementation in bar format
for 14 days also increased lymphocyte glutathione levels
[69]. De Aguilar-Nascimento et al. [71] studied patients
with ischemic stroke that were fed via a nasogastric tube
a diet with 35 kcal/kg/d and 1.2 g of protein/kg/d con-
taining whey protein and an observed reduction in IL-6
and an increase in glutathione levels after five days of
supplementation.
Furthermore, several studies also shown in different
models of oxidative stress that only whey protein or
diets that contain this protein improve antioxidant func-
tion and decrease oxidative stress [72-75].
Collectively, these findings suggest that whey protein
may act as a nutritional component to increase endogen-
ous antioxidant enzymes (glutathione peroxidase, cata-
lase, and superoxide dismutase) and to reduce oxidative
stress markers (MDA, TBARS) jointly with low expres-
sion of pro-inflammatory cytokines (IL-1β, IL-6 and
TNF-α) in obese, diabetic or stroke patients.
Commercialization and safety doses of whey protein
Whey protein can be found in drinks, powder, protein
bars, and milk. The main natural source of whey protein
is bovine milk that has approximately 3.5% protein, of
which 80% is casein and the remaining 20% is whey pro-
tein [22,76]. Whey protein concentrate also may include
2989% milk serum protein, and isolates should contain
more than 90% whey protein [22]. In addition, whey pro-
tein can also be found in the form of hydrolysates. This
form of whey protein hydrolysates aims to optimize the
physical, chemical, and nutritional properties, improving
the absorption of proteins [25].
According to the studies presented in this review, the
amount of whey protein administered to adult humans
is between 5.054.0 g at durations of approximately
12 weeks. Furthermore, no serious adverse effects were
observed with whey protein supplementation. However,
this supplementation must make part of a habitual diet.
Future perspectives
This review shows that whey protein may improve sev-
eral risk factors for DM, obesity, hypertension, oxidative
stress and MS (Figure 1). In addition, new studies
Decrease:
Oxidative stress
Figure 1 Main mechanisms of action of whey protein in protection of risk factors for metabolic diseases, such as obesity, type 2
diabetes mellitus, hypertension, oxidative stress and metabolic syndrome.
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suggest a relationship between consumption of whey
protein source foods and oxidative stress, hepatoprotec-
tive effects, and increased resting energy expenditure.
Kume et al. [62] demonstrated a hepatoprotective effect
of consumption of whey protein D-galactosamine-induced
hepatitis and liver fibrosis in rats. There was a significant
decrease in the activity of hepatic enzymes (AST: 92.5%,
ALT: 98%, LDH: 65%, hyaluronic acid: 60%) after con-
sumption of whey protein compared to casein.
In trained subjects, Hackney et al. [27] observed a sig-
nificant increase (5%) after 24 hours of resting energy
expenditure with the consumption of 18 g of whey pro-
tein before of a single session of resistance training (70
75% of one repetition maximum) when compared to an
intake of 19 g of carbohydrates. The authors speculate
that this increase occurred by the increased availability
of amino acids to skeletal muscle after whey protein in-
take. In addition, there was a decrease in respiratory
coefficients in both the consumption of carbohydrates
(5%) and whey (6%); this reduction indicates the
increased oxidation of fat. Furthermore, more studies
are needed to determine whether supplementation of
whey protein plus a balanced diet and resistance training
can increase the long-term increase in resting energy ex-
penditure and improve body composition.
Conclusions
In summary, whey protein has an attractive effect on glu-
cose metabolism control in healthy, overweight, obese,
and insulin-resistant subjects. Moreover, whey protein
assures a higher satiety; this effect is involved with the
modulation of several gut hormones related to the reduc-
tion of food intake, with increased release of anorectic
hormones, such as cholecystokinin, leptin, and GLP-1 and
decreased release of the orexigenic hormone, ghrelin; and
reduction of neuropeptide Y and increase of pro-opiome-
lanocortin in CNS. In addition, the reductions of expres-
sion of both inflammatory and oxidative stress markers, as
well as the reduction in blood pressure, are also the main
beneficial of risk factors for metabolic diseases.
Competing interests
The authors declare that they have no competing interests.
Acknowledgements
We would like to thank funding from the FAPESP.
Author details
1
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas,
Universidade de São Paulo (USP), São Paulo/SP, Brazil.
2
Laboratório de
Bioquímica e Fisiologia do Exercício, Universidade do Extremo Sul
Catarinense, Criciúma/SC, Brazil.
3
Departamento de Patologia, Universidade
Estadual Paulista (UNESP), Botucatu/SP, Brazil.
4
Departamento de Fisiologia,
Universidade Federal de São Paulo (UNIFESP), São Paulo/SP, Brazil.
5
Departamento de Psicobiologia, Universidade Federal de São Paulo
(UNIFESP), São Paulo/SP, Brazil.
6
Departamento de Clínica Médica,
Universidade Estadual de Campinas (UNICAMP), Campinas/SP, MA: 13083-
970, Brazil.
Authorscontributions
GDP was the responsible by design of whole manuscript, GTDS and GDP
wrote the paper, FSL, JCR, EPO, LMO, and RVS participated of choose and
discussion of papers included . All authors read and approved the final
manuscript.
Received: 14 February 2012 Accepted: 7 June 2012
Published: 7 June 2012
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doi:10.1186/1476-511X-11-67
Cite this article as: Sousa et al.:Dietary whey protein lessens several risk
factors for metabolic diseases: a review. Lipids in Health and Disease 2012
11:67.
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... 4,5 Evidence largely from short-term studies suggests resistance-based exercise and/or a higher intake of dietary protein [beyond the Recommended Dietary Amount (RDA)] may oppose these deleterious alterations. [6][7][8] Of the protein sources available, whey protein (a concentrated form of milk protein) contains bioactive peptides and branched-chain amino acids (notably leucine), which are released in the gastrointestinal tract during hydrolysis. 9,10 The functional properties of whey protein are purported to confer metabolic benefits on lipid metabolism, insulin resistance, and immune function. ...
... 9,10 The functional properties of whey protein are purported to confer metabolic benefits on lipid metabolism, insulin resistance, and immune function. 7,9,10 For instance, whey protein modulates incretin hormones and is highly insulinotropic, and immunoglobins present in whey protein possesses anti-inflammatory properties. 7,9,10 Epidemiological and interventional studies 9,11,12 support this by showing the benefits of whey protein on markers of cardiometabolic disease in healthy and clinical populations; however, long-term randomized controlled trials (RCTs) are needed to confirm these findings in older populations. ...
... 7,9,10 For instance, whey protein modulates incretin hormones and is highly insulinotropic, and immunoglobins present in whey protein possesses anti-inflammatory properties. 7,9,10 Epidemiological and interventional studies 9,11,12 support this by showing the benefits of whey protein on markers of cardiometabolic disease in healthy and clinical populations; however, long-term randomized controlled trials (RCTs) are needed to confirm these findings in older populations. ...
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... The soluble proteins present in milk do not participate in the coagulation process in cheese production, therefore, they are contained in the whey. These proteins are divided into different fractions, which are: β-lactoglobulin, α-lactoalbumin, bovine serum albumin (BSA), immunoglobulins, glycomacropeptides (GMP), peptone, proteases, and in a smaller amount or subfractions: lactoferrin and lac toperoxidase (LE MAUX et al., 2016;SOUSA et al., 2012). ...
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... However, previous studies have paid much attention to the effects of high protein intake (Heather & Leidy, 2014; Van et al., 2013) and dietary protein restriction (Deval et al., 2009) on physiological responses of the body. On the other hand, the functions of casein and soy protein in diets have been widely studied (Ascencio et al., 2004;Sousa et al., 2012), but the effect of meat protein has been studied very little. ...
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... Some authors emphasize that whey protein is a rich source of branched-chain amino acids (leucine, isoleucine and valine), which play a key role in the regulation of skeletal muscle protein synthesis [5][6][7]. Moreover, whey proteins reduce oxidative stress and protect from ultraviolet radiation [8]. Anti-inflammation, antioxidant and hepatoprotection are well-known effects of whey protein. ...
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