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Whey Protein's Impact on Metabolic Health

This review discusses the benefits of dietary whey protein in reducing risk factors for obesity and type 2 diabetes mellitus (DM). Whey protein has been shown to lower serum glucose levels, promote weight loss, maintain muscle mass, and improve hormonal responses related to appetite and metabolism. Additionally, it may reduce inflammation, oxidative stress, and blood pressure, making it a potential dietary strategy for managing metabolic diseases.

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0% found this document useful (0 votes)
8 views9 pages

Whey Protein's Impact on Metabolic Health

This review discusses the benefits of dietary whey protein in reducing risk factors for obesity and type 2 diabetes mellitus (DM). Whey protein has been shown to lower serum glucose levels, promote weight loss, maintain muscle mass, and improve hormonal responses related to appetite and metabolism. Additionally, it may reduce inflammation, oxidative stress, and blood pressure, making it a potential dietary strategy for managing metabolic diseases.

Uploaded by

labacha.hungque
Copyright
© All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd

Sousa et al.

Lipids in Health and Disease 2012, 11:67


[Link]

REVIEW Open Access

Dietary whey protein lessens several risk factors


for metabolic diseases: a review
Gabriela TD Sousa1, Fábio S Lira2, José C Rosa1, Erick P de Oliveira3, Lila M Oyama4, Ronaldo V Santos5 and
Gustavo D Pimentel6*

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 known to be strongly associated with cardiovascular


Excess bodyweight in humans has been increasing diseases [7].
worldwide. It is considered an epidemic by the World Reductions in body weight can reduce obesity-related
Health Organization (WHO) [1,2]. Recently, it was esti- problems [8-10]. Accordingly, dietary manipulations may
mated that more than 300 million people worldwide are promote increased satiety, to stimulate the anorexigenic
obese and more than 1 billion are overweight [3]. hormones and consequent to reduce food intake and
Similar to obesity, type 2 diabetes mellitus (DM) has body weight [11]. Therefore, is extremely important to
been regarded as a major global epidemic of the 21st discover strategies that maximize the effect of weight
century [4]. In addition, obese individuals twice as likely loss and inhibit weight regain after short- and long-term
to develop metabolic syndrome (MS) comorbidities [5]. of nutritional counseling [2,12,13]. Likewise, diet supple-
Obesity and DM are MS-associated diseases. Although mentation with milk serum protein has been suggested
the pathogenesis of MS and each of its components is as an adjunct strategy in the prevention and treatment
complex and poorly understood, abdominal obesity and of obesity and MS-related diseases in humans [14,15]
insulin resistance are recognized as risk factors for MS. and animals [16,17]. In addition, dietary milk serum pro-
Furthermore, patients with MS have a five-fold higher teins, e.g., whey protein, have high nutritional value
risk of developing DM [6]. because it contains all essential amino acids in higher
Patients with DM have an elevated response to post- concentrations than vegetable protein sources [18,19].
prandial triacylglycerols compared to non-diabetic sub- Based on that, this review aims to discuss the main
jects. Additionally, postprandial triacylglycerols are also effects of whey protein in the treatment or prevention of
obesity, DM, hypertension, oxidative stress and MS-
linked metabolic complications.

* Correspondence: gupimentel@[Link]
6
Departamento de Clínica Médica, Universidade Estadual de Campinas Methodology
(UNICAMP), Campinas/SP, MA: 13083-970, Brazil For the preparation of this review, we performed biblio-
Full list of author information is available at the end of the article graphic searches in databases of the CAPES Periodic
© 2012 Souza et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License ([Link] which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Sousa et al. Lipids in Health and Disease 2012, 11:67 Page 2 of 9
[Link]

Portal, Scielo, and Medline/Pubmed, covering articles weight loss, reduction of body fat, maintenance of
published between 2003 and 2012. A search of articles muscle mass and satiety control [10,13,14,29,35-37].
was made using the key words “whey protein,” “milk Frestedt et al. [10] demonstrated that the supplemen-
serum protein,” “type 2 diabetes mellitus,” “obesity,” tation with a mixture of whey protein isolate with other
“insulin resistance,” “inflammation,” “hypertension,” peptides (2 servings/day and each serving with 10 g pro-
“metabolic syndrome,” and “protein hydrolysates.” tein) for 54 healthy subjects for 12 weeks, in addition to
47 control subjects who consumed glucose (10 g/serv-
Main nutritional and functional components of whey ing) led to weight loss in both groups, but the group
protein supplemented with whey protein had higher weight loss.
Milk serum proteins are defined as substances that They also had greater reductions of body fat (6.1%) and
remain soluble in milk serum [20]. These proteins are a higher maintenance of lean mass than the control
naturally formed during the production of cheese [19,21] group who had consumed just glucose.
and account for 20% of the all protein in milk [21-23], Pilvi et al. [13] studied mice that had diet-induced
such as β-lactoglobulins, α-lactalbumin, immunoglobu- obesity and were subsequently fed a low-calorie diet with
lins, lactoferrin, lactoperoxidase, glycomacropeptide, different types of proteins (whey protein isolate, α-lactal-
bovine serum albumin [18,20,22,24], and other proteins bumin, β-lactoglobulin, and lactoferrin) for 50 days, and
[22]. after this period, they returned to high fat diet. The mice
In addition, whey protein has high concentrations of that consumed α-lactalbumin (45.9 g) had a significant
branched chain amino acids (BCAAs), such as leucine, loss of fat mass during the caloric restriction period and
isoleucine, and valine, which are also related to import- a reduction in visceral fat during the weight recovery
ant factors for muscle growth, build, and repair [14,25]. period when compared to other groups. But this is not a
Milk serum proteins do not coagulate in acidic condi- conclusive explanation about the mechanisms that lead
tions; they resist the action of quimosine from the stom- to such results.
ach, quickly reach the jejunum [19], are rapidly digested, Another component of milk, calcium, has been exten-
and raise plasma amino acid concentrations of [21,26]. sively studied with a possible anti-obesity role. But Pilvi
Therefore, milk serum proteins perform several func- et al. [29] observed a significant decrease in weight gain
tions, such as mineral absorption, improvement of pro- and body fat and a higher fat excretion in mice fed for
tein synthesis, sensitivity to hormones, and decreased 21 weeks with high-fat diet (60% of total calories from
blood glucose and lipid levels [7,15,16,21,23,27-29]. In fat), 18% protein (whey protein isolate), and 1.8% cal-
summary, the main nutritional and functional compo- cium carbonate (CaCO3) in comparison with a similar
nents of whey protein are presented in Table 1. diet that had casein as the protein source. The authors
suggest that a possible explanation for this result is the
Improvement risk factors for metabolic diseases high levels of leucine present in the whey protein, e.g.,
Obesity the leucine may modulate insulin signaling by phospha-
Several types of diets are being studied to find a model tidylinositol 3 kinase (PI3K) directing the energy to
that has the quality and quantity of nutrients to promote muscle synthesis and not for storage in adipose tissue.

Table 1 Main components and actions of whey protein


Components Actions
β-lactoglobulin Has content higher of branched chain amino acids (~25.1%). Capture
(45–57%) hydrophobic molecules, participating in the reduction of intestinal
absorption of lipids.
α-lactalbumin Has content higher of tryptophan (6%) of all dietary proteins. It is rich
(15–25%) in lysine, leucine, threonine, and cysteine. It has the ability to bind to
minerals such as Ca and Zn, positively affecting their absorption.
Immunoglobulin Four classes of immunoglobulins are present in serum: IgG, IgA, IgM,
(10–15%) 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 (10–15%) 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].
Sousa et al. Lipids in Health and Disease 2012, 11:67 Page 3 of 9
[Link]

Subsequently, Pilvi et al. [38] showed that mice that con- 12 weeks of supplementation with 54 g of whey protein
sumed a high-fat diet (60% of total calories from fat) compared to control group (without supplementation)
with 18% protein (whey protein isolate) and 1.8% cal- and with consumption of the same amount of glucose.
cium carbonate for 12 weeks had not only an inhibition As a reduction of ~20% in serum triacylglycerols has
in the accumulation of fat mass but also an increase in been shown to reduce the progression of coronary dis-
gene expression in the visceral adipose tissue of leptin eases, these results are very important to decreasing
and β3-adrenergic receptor when compared to another obesity.
group of mice that received a diet with similar fat and Kasim-Karakas et al. [40] studied the influence of the
protein contents, that instead used casein instead of ingestion of whey protein in overweight and obese
whey and only 0.4% calcium carbonate. Thus, the women with polycystic ovary syndrome (PCOS). It has
authors suggest that the whey protein isolate may reduce been known that a reduction in body weight improves
obesity via improvement of leptin sensibility. the symptoms of PCOS. Accordingly, the intake of 75 g
Baer et al. [35] showed that the type of protein can in- of whey protein isolate compared to 75 g of glucose
fluence the weight loss response. Supplementation with reduced the ghrelin levels for 5 hours after consumption.
56 g of whey protein (consumed twice daily) for 23 weeks Therefore, these results also suggest that the whey pro-
diminished body weight and fat mass when compared tein can prolong satiety.
with the group that consumed just carbohydrates. More- Recently, Pal and Ellis [41] showed in overweight and
over, waist circumference and fasting ghrelin levels were obese individuals that supplementation of whey protein
lower in the whey protein group when compared to the (54 g) for 12 weeks did not significantly reduce the body
group that ingested soy protein. These results demon- weight, BMI, waist circumference, and total body fat, but
strated that through yet-unknown mechanisms, different decreases the triacylglycerol and insulin levels after
sources of dietary protein may differentially facilitate treatment.
weight loss and affect body composition. Collectively, these studies that relationship whey pro-
In addition to the type dietary of protein, the propor- tein and obesity showed improvement in insulin sensitiv-
tion of nutrients also influences energy consumption ity and lipid profile with possible increase of energy
and body composition [37]. Pichon et al. [37] observed a expenditure.
reduction in body weight and adipose tissue in rats after
25 days of consuming a high-protein diet (55% of total Type 2 diabetes mellitus
energy intake) compared to rats that consumed a normal Although insulin is a hormone anorectic [42-45] and
protein diet (14% of energy). In addition, the results suppresses ghrelin [40], it is also an anabolic hormone
were more pronounced with the high protein diet con- and therefore is related to increases in muscle protein
taining whey protein isolate enriched with β-lactoglobu- synthesis [42]. Furthermore, hyperinsulinemia inhibits
lin compared with other protein sources, such as whole hormone sensitive lipase (HSL), suppressing the release
milk and whey protein concentrate. The authors sug- of fatty acids from adipose tissue [7] and stimulates the
gested that these results were obtained because the pro- lipoprotein lipase (LPL) and fatty acid synthesis, contrib-
teins have a greater power of satiety when compared to uting to obesity [40]. However, the increase in insulin
the other nutrients. Moreover, β-lactoglobulin may cap- levels after consumption of whey protein reported in
ture hydrophobic molecules, decreasing the absorption several studies is not able to promote the increase of fat
of fat by intestinal cells. Furthermore, a high protein diet mass, perhaps due to the high leucine contents present
induces to increases in thermogenesis [20]. in whey protein and also because its consumption over
Furthermore, the reduction of body weight and body the long-term (>12 weeks) improves insulin sensitivity
fat [9] and the decrease of serum triacylglycerols levels [41].
in obese individuals are extremely important, since these Recent studies have shown the important role of whey
individuals are at increased risk for cardiovascular dis- protein supplementation in glycemia control, possibly
eases [23,26]. Recently, Mortensen et al. [7] showed a through the stimulation of incretin hormones, which in-
decrease in triacylglycerol levels when whey protein was crease fasting and postprandial insulin release and im-
supplemented in DM patients. In addition, Pal et al. [23] prove insulin sensitivity [41,46-48].
confirmed these results in both overweight and obese Pichon et al. [37] showed that a high-protein diet
post-menopausal women. This reduction was found after raises insulin concentrations compared to a normopro-
consumption of 45 g of whey protein isolate together teic diet. However, in human and rat studies in which
with a high-fat meal when compared to consumption of the protein is combined with carbohydrate, an increase
the equivalent amount of glucose or casein. Pal et al. in the insulin response has been observed [14-16]. In
[39] also showed a decrease in triacylglycerol concentra- addition, whey protein stimulates insulin secretion, and
tion in both overweight and obese individuals after when compared to casein, milk serum proteins have
Sousa et al. Lipids in Health and Disease 2012, 11:67 Page 4 of 9
[Link]

increased postprandial insulinotropic effects that are the secretion postprandial GLP-1 is decreased [15,49]
probably mediated by the rapid serum absorption of and the enzyme activity DDP-IV is increased [50].
BCAAs, the improvement in glucose homeostasis in In healthy individuals, an increased GLP-1 levels due
DM, and the possible delay or withdraw of the medicine to consumption of whey protein is more palatable [51].
[46] . Recently, Veldhorst et al. [51] observed an increase in
Recently, Gunnarsson et al. [16] showed the effects of blood insulin (91%) and GLP-1 (164%) levels after con-
acute administration of whey protein plus glucose by sumption of a diet containing 25% of calories from pro-
nasogastric tube (enteral diet) in mice when compared tein (whey protein), 55% from carbohydrates, and 20%
to the administration of only glucose. In this study, the from lipids compared to similar quantities of casein. In
authors found an increase in insulin levels three times addition, non-significant reduction of blood glucose with
greater and an insulin tolerance four times greater with the consumption of whey compared to casein was
consumption of whey protein. observed.
Petersen et al. [15] observed in healthy subjects a sig- In summary, protein is important in fetal growth and
nificant reduction in postprandial glucose (37.5%) when development of the pancreas. Furthermore, adaptations
consumed in a single dose containing 50 g of carbohy- to nutritional stress may permanently alter the physi-
drate plus milk serum proteins (20 g in total). This de- ology and metabolism of several organs, leading to long-
crease was dose-dependent; thus, the higher the protein term diseases such as cardiovascular diseases, DM, and
intake, the greater its effect on blood glucose. The same MS [24]. Likewise, Barnett et al. [24] observed reduction
effect was observed by Frid et al. [46] in DM subjects of 55–65% in insulin secretion in adult life in the off-
that consumed milk serum protein. In this study, the spring of mother rats who consumed low amounts of
authors found a significant increase in insulin and glu- protein (whey protein) during pregnancy. This reduction
cose-dependent insulinotropic peptide (GIP). is related to the early development of DM in adult
Recently, Mortensen et al. [7] confirmed the humans.
hypoglycemic effect of whey protein in individuals with Therefore, whey protein may be utilized by reduce in-
DM within eight hours of consuming a meal test that sulin resistance due the increase in secretion of GLP-1
contained 45 g of whey protein compared to three other and to reduce serum glucose and insulin levels.
meals containing different protein sources, casein, glu-
ten, and codfish. Moreover, within six hours of a meal
test a reduction in triacylglycerol concentrations was Hypertension
observed with the supplementation of whey compared Hypertension is commonly found in patients with DM
to three other meals that contained a different type of and may affect approximately 60% of Brazilian indivi-
protein. Interestingly, all protein meals were associated duals [52].
with a high-fat diet (100 g of butter). Recently, it was discovered that diet is a major deter-
Lan-Pidhainy and Wolever [28] also observed a signifi- minant of blood pressure. Likewise, certain foods have a
cant hypoglycemic effect in individuals with insulin re- direct role in the reduction of blood pressure or add-
sistance after the consumption of a drink containing itional reductions in cardiovascular mortality [41,53].
30 g of whey protein plus 50 g of glucose compared to Some amino acids of the whey protein, e.g., α-lactalbu-
groups of individuals who consumed only 50 g glucose min and β-lactoglobulin, are precursors of peptide inhi-
or another group who consumed 50 g of glucose plus bitors of angiotensin-converting enzyme (ACE) [20].
30 g of canola oil. ACE is a key enzyme in the regulation of blood pressure
Studies performed in rats [16,17] showed that supple- [41].
mentation with whey protein possibly suppressed serum Pal and Ellis [41] showed the hypotensive effect that
glucose level by the inhibition of the enzyme dipeptidyl occurs after intake of whey protein (54 g protein) and
peptidase-IV (DPP-IV), whose function is to disable the casein (27 g protein) in either obese or overweight
incretin hormones, such as GLP-1 (glucagon-like peptide normotensive individuals. However, the components of
1) and GIP, which are both related to glycemic control. proteins that could possibly lead to the improvement of
Gunnarsson et al. [16] suggest, in mice, that the diges- blood pressure were not analyzed in this study. Likewise,
tion of whey protein leads to the formation of di- and Lee et al. [54] found no decrease in blood pressure in
tri-peptides that are a substrate for DPP-IV. Neverthe- individuals with mild hypertension who consumed a
less, Frid et al. [46] and Mortensen et al. [7] found no drink containing skim milk with milk serum proteins
changes in blood GLP-1 levels, only decreased glucose (125 mL) for 12 weeks. The low level of peptides (2.6 g
levels after consumption of different amounts, 36.4 g per 100 g of protein drink) administered together with
and 45 g of whey protein in DM individuals. These find- protein may have been responsible for the absence of an
ings may possibly occur because, in diabetic subjects, effect on blood pressure.
Sousa et al. Lipids in Health and Disease 2012, 11:67 Page 5 of 9
[Link]

In summary, whey protein is associated with reduction Therefore, we may to infer that probably a dose of whey
blood pressure by inhibition of ACE enzyme and pos- was insufficient to stimulate the CCK.
sibly via lower body weight gain in individuals that Pal and Ellis [41] observed a significant decrease in
habitually consumed the aminoacids from whey protein glucose, appetite, and food intake, and an increase in
or BCAA than those subjects that consumption others serum insulin levels after the consumption of a drink
aminoacids, for e.g. non essential. Therefore, whey pro- containing 50 g of whey protein when compared to the
tein can in the future be considered extremely important consumption of a similar amount of protein tuna, tur-
for the control of hypertension. key, or egg albumin. This study suggests a potential
application of these foods in appetite control in both
overweight and obese individuals.
Possible mechanisms involved in reducing risk factors for Furthermore, other amino acids not described in this
metabolic diseases review are also associated with satiety, such as tryptophan,
Reduction of food intake which is a precursor of serotonin and an important modu-
Satiety is an important factor in the regulation of food lator of appetite [51].
intake and also in the control of obesity [11,45]. Dietary Although the gut hormones are known by increase of
protein and specific amino acids are involved in the con- anorexigenic hormones, also was observed that the leu-
trol of gastric and intestinal motility and in pancreatic cine when injected directly in the central nervous system
secretion, and are more potent in inducing satiety than reduces the food intake and body weight [60]. Further-
carbohydrates or fats [55]. more, Ropelle et al. [61] found that both leucine intra-
Gut peptides that regulate the digestive process and cerebroventricular injection or high-protein diet
neuronal signaling in the central nervous system (CNS) decrease AMPK and increase mTOR phosphorylation in
regulate hunger and satiety [42]. Table 2 lists several the CNS inhibiting the neuropeptide Y and stimulating
peripheral hormones and their roles in the regulation of the pro-opiomelanocortin expression, leading to reduc-
food intake [57]. tion of food intake.
Milk serum proteins are more potent stimulants of In summary, these findings suggesting that the aminoa-
cholecystokinin (CCK) and GLP-1 than casein cids from whey protein may reduce the food intake via in-
[26,41,51]. Among the peptides involved with whey pro- crease of gut hormones (CCK and GLP-1), and reduction
tein, glycomacropeptide is an effective secretagogue of of neuropeptide orexigenic (NPY) and increase of neuro-
CCK [36]. CCK is a hormone secreted by I cells of the peptide anorexigenic (POMC) in the hypothalamus.
small intestine that has as one of its functions to modu-
late satiety [59]. However, Burton-Freeman [36] did not Anti-inflammatory actions
observe the effect of dietary whey protein on the Adipose tissue is an endocrine organ that releases hor-
increase of postprandial CCK levels in healthy subjects. mones, cytokines, and others substances that tend to im-
pair insulin sensitivity [55]. Obese individuals have
increased secretion of adipocytokines by adipose tissue
Table 2 Characteristics and functions of hormones
and macrophages [20].
related to appetite regulation
Recently, Pal & Ellis [41] observed in overweight and
Hormones Production and effects
obese subjects that the supplementation of whey protein
CCK Produced: duodenum
(54 g) for 12 weeks did not change the pro-inflammatory
Effect: reduces appetite markers (IL-6, C-reactive protein-CRP, and TNF-α).
GLP-1 Produced: mainly in distal intestine (L cells) However, in D-galactosamine-induced hepatitis and liver
Effect: reduces appetite fibrosis in rats, the consumption of whey protein
Ghrelin Produced: stomach strongly reduced the plasma levels of pro-inflammatory
cytokines (IL-1 beta: 59% and IL-6: 29%) compared to
Effect: stimulates appetite
the consumption of the same amount of casein [62].
GIP Produced: K cells of the duodenum
Collectively, reduction of pro-inflammatory cytokines
Effect: reduces appetite and potentiate insulin release may be associated with reduction of body weight gain
Leptin Produced: mainly in adipose tissue after consumption of whey protein and it aminoacids.
Effect: suppress appetite
Uroguanylin [56] Produced: intestinal epithelial cells Anti-oxidative stress actions
Oxidative stress has been associated with MS, which is a
Effect: reduces appetite
disease recognized by inflammatory effects that are
CCK: cholecystokinin, GLP-1: glucagon-like peptide 1, GIP: glucose-dependent
insulinotropic peptide. Adapted: Pimentel & Zemdegs, 2010 [57] and Pimentel
linked with the activation of reactive oxygen species
et al. [58]. (ROS) [63-65]. Nowadays, indicators that are more
Sousa et al. Lipids in Health and Disease 2012, 11:67 Page 6 of 9
[Link]

typically used in the evaluation of ROS are the endogen- Furthermore, several studies also shown in different
ous antioxidant enzymes such as glutathione peroxidase, models of oxidative stress that only whey protein or
catalase, and superoxide dismutase, and other compo- diets that contain this protein improve antioxidant func-
nents such as malondialdehyde (MDA) and thiobarbitu- tion and decrease oxidative stress [72-75].
ric acid reactive substances (TBARS) [63-66]. Recently, Collectively, these findings suggest that whey protein
the administration of 100 mg/kg of body weight of whey may act as a nutritional component to increase endogen-
protein in streptozotocin-induced diabetic rats was ous antioxidant enzymes (glutathione peroxidase, cata-
found to decrease several oxidative stress indicators, lase, and superoxide dismutase) and to reduce oxidative
such as MDA, nitric oxide, and ROS concentrations; as stress markers (MDA, TBARS) jointly with low expres-
well as reduction of pro-inflammatory cytokines (IL-1β, sion of pro-inflammatory cytokines (IL-1β, IL-6 and
TNF-α, IL-6 and IL-4) and increase glutathione levels TNF-α) in obese, diabetic or stroke patients.
[67]. Another study observed that rats fed high-carbohy-
drate, fat-free diets to induce fatty livers (nonalcoholic Commercialization and safety doses of whey protein
fatty liver model) plus orally administered whey protein Whey protein can be found in drinks, powder, protein
(0.15 g/d/rat) for 28 days reduced MDA and increased bars, and milk. The main natural source of whey protein
glutathione levels [68]. is bovine milk that has approximately 3.5% protein, of
Haraguchi et al. [19] found a protective effect against which 80% is casein and the remaining 20% is whey pro-
oxidative stress, mainly in the liver, and a beneficial ef- tein [22,76]. Whey protein concentrate also may include
fect on renal function in rats supplemented with whey 29–89% milk serum protein, and isolates should contain
protein plus a hypercholesterolemic diet, but they did more than 90% whey protein [22]. In addition, whey pro-
not observe a reduction in serum cholesterol levels. tein can also be found in the form of hydrolysates. This
In human studies, beneficial effects in the reduction of form of whey protein hydrolysates aims to optimize the
oxidative stress after treatment with whey protein [69- physical, chemical, and nutritional properties, improving
71]. Likewise, supplementation with 20 g/d of whey pro- the absorption of proteins [25].
tein isolate for 12 weeks in subjects with nonalcoholic According to the studies presented in this review, the
steatohepatitis was found to increase the glutathione and amount of whey protein administered to adult humans
total antioxidant capacities [70]. In healthy individuals, is between 5.0–54.0 g at durations of approximately
45 g/day of whey protein supplementation in bar format 12 weeks. Furthermore, no serious adverse effects were
for 14 days also increased lymphocyte glutathione levels observed with whey protein supplementation. However,
[69]. De Aguilar-Nascimento et al. [71] studied patients this supplementation must make part of a habitual diet.
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- Future perspectives
taining whey protein and an observed reduction in IL-6 This review shows that whey protein may improve sev-
and an increase in glutathione levels after five days of eral risk factors for DM, obesity, hypertension, oxidative
supplementation. 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.
Sousa et al. Lipids in Health and Disease 2012, 11:67 Page 7 of 9
[Link]

suggest a relationship between consumption of whey Authors’ contributions


protein source foods and oxidative stress, hepatoprotec- 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
tive effects, and increased resting energy expenditure. discussion of papers included . All authors read and approved the final
Kume et al. [62] demonstrated a hepatoprotective effect manuscript.
of consumption of whey protein D-galactosamine-induced
Received: 14 February 2012 Accepted: 7 June 2012
hepatitis and liver fibrosis in rats. There was a significant Published: 7 June 2012
decrease in the activity of hepatic enzymes (AST: 92.5%,
ALT: 98%, LDH: 65%, hyaluronic acid: 60%) after con- References
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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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