HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Luhovyy, B. L. Articles by Anderson, G. H. Search for Related Content PubMed PubMed Citation Articles by Luhovyy, B. L. Articles by Anderson, G. H.

Whey Proteins in the Regulation of Food Intake and Satiety

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, CANADA

Address correspondence to: Bohdan L. Luhovyy, PhD, Department of Nutritional Sciences, University of Toronto, Rm 329, FitzGerald Building, 150 College St, Toronto, Ontario, CANADA M5S 3E2. E-mail: bohdan.luhovyy{at}utoronto.ca

	ABSTRACT

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
Whey protein has potential as a functional food component to contribute to the regulation of body weight by providing satiety signals that affect both short-term and long-term food intake regulation. Because whey is an inexpensive source of high nutritional quality protein, the utilization of whey as a physiologically functional food ingredient for weight management is of current interest. At present, the role of individual whey proteins and peptides in contributing to food intake regulation has not been fully defined. However,

• Whey protein reduces short-term food intake relative to placebo, carbohydrate and other proteins.
  
• Whey protein affects satiation and satiety by the actions of: (1) whey protein fractions per se; (2) bioactive peptides; (3) amino-acids released after digestion; (4) combined action of whey protein and/or peptides and/or amino acids with other milk constituents.
  
• Whey ingestion activates many components of the food intake regulatory system.
  
• Whey protein is insulinotropic, and whey-born peptides affect the renin-angiotensin system.
  

It remains unclear, however, if the favourable effects of whey on food intake, subjective satiety and intake regulatory mechanisms in humans are obtained from usual serving sizes of dairy products. The effects described have been observed in short-term experiments and when whey is consumed in much higher amounts.

Key words: whey proteins, food intake, satiety, weight management

	Introduction

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
Dietary regulation of food intake by dairy products and their components has potential to contribute to the prevention and management of the obesity pandemic. Food ingestion triggers multiple physiologic responses that affect food intake regulation and induce satiety. The challenge is to understand the relative importance of food components and how to optimize their interaction with the food intake regulatory system [1].

A positive association between dairy consumption and the maintenance of healthy body weights [2–5] has prompted investigations into the effects of milk components on determinants of energy balance. Calcium [6,7], medium-chain triglycerides [8] and conjugated linoleic acid [9] have been established as factors modulating lipid metabolism and energy expenditure. Dairy products and dairy components are known to suppress short-term food intake, increase subjective satiety and stimulate the mechanisms known to signal satiation and satiety [10]. However, the contribution of total milk protein and of the major protein fractions of milk, e.g. caseins or whey, and their individual components in short- and long-term regulation of food intake and satiety has received little attention, even though protein suppresses short-term food intake more than either carbohydrate or fat [11], and there is evidence that high protein diets are more satiating than low protein diets [12,13].

Because milk whey is an abundant by-product in cheese manufacture (9L of whey are produced from 10L of milk during cheese making [14]) it is inexpensive source of high nutritional quality protein for uses as a physiologically functional food ingredient. Therefore the role of whey protein in food intake regulation is reviewed in this paper.

	Whey Proteins: Nomenclature and Commercial Whey Products

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
The latest (sixth) revision of nomenclature for proteins of cows’ milk defines whey proteins as the group of milk proteins that remain soluble in milk serum or whey after precipitation of caseins at pH 4.6 and 20°C and this group includes β-Lactglobulin (β-LG), -Lactalbumin (-LA), serum albumin (SA), immunoglobulins (Ig), lactoferrin (LF) and proteose-peptone fractions [15]. Broader classifications assign LF, lactoperoxidase (LP), β-microglobulin, lysozyme (LYZ), insulin-like growth factor (IGF), -globulins and several other small proteins to minor whey proteins [16]. Although caseinomacropeptide (CMP) originally derives from -casein, it is considered to be a sweet whey constituent, because bovine -casein is hydrolysed by chymosin during cheese-making into para--casein (residues 1–105), which remains with the curd, and CMP (residues 106–169), which is removed with the whey [17]. Total protein content and the ratio between protein fractions in milk differ due to interspecies differences. For example, total protein content in human milk is 1% but in cow milk is 3.4%; the ratio of whey: casein is 60:40 in human milk, 50:50 in equine (mare's) milk, while in the cow, goat, sheep and buffalo milks it is 20:80 [18]. Human and bovine whey protein fractions also differ in their qualitative profiles. For instance, human whey contains 25% of -LA, but bovine whey has only 5% of this fraction and conversely β-LG does not occur in human, rat, mouse or guinea pig milks whereas it is a major protein in bovine milk, representing about 50% of total whey protein and 12% of the total protein of cow milk [18,19].

Whey products on the market encompass: sweet and acid whey powders, reduced lactose whey, demineralized whey, whey protein concentrates with protein contents of: 34% (WPC34), 50% (WPC50), 60% (WPC60), 75% (WPC75), 80% (WPC80), whey protein isolate (WPI) containing not less than 90% of protein, lactoferrin, lactoperoxidase, glycomacropeptide (GMP), dairy product solids (permeate) and mineral-concentrated whey (reduced lactose whey) [20]. The technological implications of whey products as excellent additives to improve food formulation have been proposed for a broad range of foods due to their functional benefits in processing such as solubility, water-binding and viscosity, gelling, emulsification, whipping, foaming and aeration, dispersibility, edible film formation, antioxidant activity, adhesion property and heat-induced browning [21]. These values are important for design of functional foods of various consistences, textures, and flavors suitable for different groups of consumers, from newborns to persons with special needs.

	Physiologic Functionality of Milk Proteins

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
The differences in the physical properties of casein and whey that contribute to their functionality in food systems also contribute to their differences in physiological effects when ingested, including their effect on food intake. Whey protein is rapidly digested whereas casein is more slowly digested. Both proteins contribute to satiety after the digestion of dairy products. However it is the ready availability of whey protein as a by-product of cheese making that has encouraged more extensive investigation of its functional effects in the regulation of food intake and metabolism.

The classification of casein and whey as "slow" and "fast" protein is based on their contribution to protein synthesis and their effect on plasma amino acid concentrations [22]. In humans, intake of whey (0.45 g/kg BW) results in a fast, but short and transient increase in plasma amino acids that peak in 40 min to 2 hours after its ingestion and returns to baseline values after 3 to 4 hours. Casein, in contrast and consistent with its slow gastric emptying, results in plasma amino acid concentrations that rise more slowly and are lower, but sustain a prolonged plateau lasting for at least 7 hours after its consumption [22,23]. The synergism between whey and casein has been confirmed in a recent human study with a milk soluble protein isolate that contained mostly whey proteins. Despite its high Protein Digestibility Corrected Amino Acid Score, the rate of amino acid delivery was too rapid to sustain the anabolic requirement during the postprandial period, while complete milk protein markedly improved dietary protein utilization measured with ¹⁵N-labeled proteins [24].

	Whey Proteins: Physiologic Functionality

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
The growing interest in bioactive ingredients from the dairy sector has increased attention on milk-based ingredients and related novel technologies aimed at the recovery of bioactive components from milk, whey and colostrum and in maintaining their stability in different food matrices and their optimal bioavailability in the body in order to deliver expected health effects [25]. Whey ingredients are used in newborn feeding formulas and in a variety of products appealing to nutrition-conscious consumers and for athletes. They can be consumed as protein drink mixes, sport meals, protein bars, high-protein cookies and in tablet form [26].

Almost all whey proteins possess bioactivities per se and are used as ingredients in many commercial products [27–30] claiming health benefits. [31]. Bioactive peptides are generated from whey proteins both in vivo during the digestion in the gastrointestinal tract and in vitro by the action of milk proteases or enzymes from starter cultures or even after consequent actions of microbial and digestive proteases. A number of commercial functional products with whey-derived bioactive peptides fractions are available on the market and claimed to have health benefits [31]. Many bioactive peptides, named due to their first discovered activity, are now considered as multifunctional peptides [32,33]. For example, -lactorphin has opioid activity, but it also inhibits the angiotensin converting enzyme (ACE) to have an antihypertensive effect [32]. Almost all known whey-derived bioactive peptides can be generated by digestive proteases. Alpha-lactorphin and lactoferricin are released after cleavage by pepsin of -LA and LF, respectively. Albutensin-A is generated by trypsin proteolysis of bovine SA, but β-lactorphin after the combined action of pepsin and trypsin [32].

Bioactive peptides exert their effects by binding to specific receptors in the intestinal lumen or in target organs and tissues after absorption into bloodstream. The growing body of data about interactions between food-born peptides and receptors in the gastro-intestinal tract supports a role for peptides in the regulation of physiologic functions. Short peptides appear in the blood as a result of paracellular transport of short peptides through the intercellular junctions [34] but larger peptides (more than 4 residues) can be transported via carriers. Their susceptibility to brush border peptidases is the primary factor that decides the transport rate [35].

Peptides derived from whey have a number of physiologic functions including modulation of blood pressure, inflammatory processes, hyperglycemia and systems regulating food intake. However these actions are not limited only to whey proteins and peptides, but also due to synergism between whey proteins and other whey constituents such as calcium. For example, the effect of milk with calcium in attenuating weight and fat gain and in reducing blood pressure is much stronger than that of calcium supplementation alone [36].

Blood Pressure.
Whey proteins (-LA and β-LG) are precursors of ACE-inhibitory peptides named lactokinins [33] which have antihypertensive and potentially anti-obesogenic activities. Other whey-born multifunctional peptides called -Lactorphin and β-Lactorphin [32] affect adipocyte lipogenesis due to their ACE-inhibitory activities and also they may reduce food intake via peripheral opioid receptors, similarly to casein and soy protein hydrolysates [37,38].

Inflammatory Response.
An increase of inflammatory cytokines and macrophage cells infiltrating the white adipose tissue are observed in obese subjects [39]. On the other hand, ACE-inhibitors and Ang-II receptors blockers are effective for both hypertension and inflammation [40]. Therefore, inflammatory responses of whey might have beneficial role for both obesity and hypertension as components of metabolic syndrome. Whey protein, unlike casein, strongly reduces the level of inflammatory cytokines (IL-1β and IL-6) and AST, ALT, LD and bilirubin in D-galactosamine-induced hepatitis in rats [41]. Thus, the beneficial effect of whey protein on hypertension may be mediated by its affect on inflammation as well as the renin-angiotensin system (RAS). ACE-inhibitors used in the management of hypertension have anti-inflammatory properties [40]. Recent data demonstrates that adipocytes have an autocrine/paracrine renin-angiotensin system and that adipocyte lypogenesis is regulated in part by angiotensin II. RAS inhibition mildly attenuates obesity in mice and there is some clinical evidence of this effect in hypertensive patients [36].

Insulinotropic Properties of Dairy Protein.
Milk consumption modifies the insulinemic and glycemic response to carbohydrate-rich food in both type II diabetic and healthy subjects [42]. A population-based prospective study (CARDIA) revealed that dairy consumption was inversely associated with the incidence of all components of the insulin resistance syndrome (IRS) among overweight individuals (BMI>=25kg/m²). Each daily occasion of dairy consumption was associated with 21% lower odds of IRS. These associations were similar for blacks and whites and for men and women [43]. Of the milk proteins, whey leads to higher pre-meal insulin concentrations than casein [44] and may contain the predominant insulin secretagogue because the insulin area under the curve (AUC) after preloads of 25 g carbohydrate with 18.2 g of whey protein was 50% higher than after milk or cheese [42]. Addition of whey to a meal containing rapidly digested and absorbed carbohydrates, stimulated greater plasma insulin concentrations (+57% after lunch) and reduced postprandial blood glucose (–21% at 120 min AUC) in type II diabetic subjects [45]. Amino acids may be the primary factor accounting for the insulinotropic effect of whey protein. Healthy subjects that ingested mixture of leucine, isoleucine, valine, lysine and threonine resulted in glycemic and insulinemic responses similar to those after whey ingestion [46] suggesting that branched-chain amino acids (BCAAs) are the major determinants of insulinemia as well as lowered glycemia caused by the whey drink. However the BCAA mixture did not stimulate incretin (GIP and GLP-1) response while the whey drink did suggesting that the action of whey is not simply related to amino acid content and presumably due to the action of peptides. The authors concluded that whey-induced hyperinsulinemia occurs by two or even more separate pathways, one connected to the significant increment in certain amino acids but the other connected through the incretins, which are believed to interact with bioactive peptides derived from proteins [46].

Food Intake Regulation.
Bioactive peptides from protein digestion have a direct effect on food intake suppression via the gastrointiestinal tract. For example, peripheral opioid and cholecystokinin (CCK)-A receptors are activated by ingestion of casein and blocking the receptors with antagonists reduces their effect on food intake [37,38]. While whey proteins are precursors of many bioactive peptides that have potential to exert their actions through gut satiety mechanisms, their mechanism of action remains to be evaluated.

	Whey Protein and Food Intake Regulation

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
The effect of protein on food intake is source dependent. The effect of whey protein on short-term food intake in humans is stronger than after casein, soy protein and egg albumin [47]. However, the effect of source is modified by many factors including dose, form (solid vs. liquid), duration to next meal and the formulation of the treatment, the presence or absence of other macronutrients, and in the case of whey, the amount of GMP. For example, whey protein (45 g, 15% GMP) suppressed food intake more than egg albumin and soy protein at a pizza meal 60 min later in young men [47] when the proteins were provided alone in the form of sweetened beverages. However, whey (< 5% GMP) and casein (50 g) similarly affected intake reduction at a pizza meal 90 min later but at 150 min casein suppressed food intake more than whey [48]. In contrast, a liquid preload containing 48 g of whey (GMP content not defined) with carbohydrate resulted in lower ad libitum intake of a buffet meal 90 min later than a preload containing the same amount of casein and carbohydrate [49]. When time until a buffet meal was 3 hours, food intake was not different after 52 g [50] or 50 g [51] preload of whey (GMP content not reported), and it was not different from casein [50] or gluten and soy protein preloads consumed as beverages containing carbohydrate [51].

The contribution of individual whey components derived from casein on food intake regulation is also of interest. CMP, which is the precursor protein for GMP, is derived from casein is a byproduct of renneting and a component of whey (1.2–1.5 g/L [14]). More than 20 years ago, it was shown that GMP can influence gastrointestinal functions by the inhibition of gastric secretion [52] and such action can be mediated via peptide hormones like cholecystokinin (CCK) [53,54], a potent satiety signal. CCK-like activity of GMP was confirmed by consecutive studies [55,56]. However it had no effect on subjective satiety and on food intake 60 min later when given in 100 ml of a 0.4% or 2% CMP solution as preloads [57]. The authors suggest that the lack of effect was due to inadequate CMP concentration, timing of CMP administration, or heterogeneity of tested CMP preparation, especially its GMP content [57]. The reason is very important because the effects claimed for CMP can be affected by its composition or preparation. About 60% of bovine CMP is glycosylated (GMP), and at least 14 different forms with different rate of glycosylation were found in genetic variant A of bovine CMP and this percentage can be affected by storage or physical treatment, e.g. heating [14]. Therefore, for CMP studies it is very important to know the composition of the preparation used. However, in contrast to its expected effect in reducing food intake, GMP in formula (13 g/L) increased food intake in Macaca rhesus infants compared to other formulas [58]. Thus the effect of this component of whey on food intake remains uncertain.

The classification of whey proteins as "fast proteins", and of caseins as "slow proteins" [22] is consistent with their reported effect on food intake in humans. Whey has been found to reduce food intake more at 90 min but casein to have a stronger effect later (at 150 min) [48]. Whey proteins after ingestion pass quickly through the stomach and reach the jejunum as intact proteins, whereas the release of casein from the stomach is delayed because in the acid environment a clot is formed. After peptic hydrolysis, peptides are released to the small intestine. In the small intestine hydrolysis of whey proteins has been reported to be slow compared to other proteins and their digestion and absorption take place over a greater length of intestine [16,22,59]. However, based on plasma amino acid concentrations, it is clear that the digestion of whey and absorption of its amino acids are faster than for casein. Similarly, rats given preloads of whey suppress food intake more than casein in the first hour of feeding 30 min after the administration of the preloads [60]. Thus, it is possible that milk-born satiation and satiety are the result of synergistic action of whey proteins providing early and casein providing overlapping but later signals.

Whey proteins contain all the essential amino acids and are ranked with the highest quality proteins [61]. The protein efficiency ratio (PER), which reflects the weight gain of young animals per gram of protein consumed over four weeks is very high for whey proteins (3.2) and higher than for casein (2.6). However, the amino acid composition of whey is also of interest for reasons other than their contribution assessed by traditional measures of nutritional quality. Its amino acid composition may also be a factor in its effect on food intake. Whey proteins, compared to other food proteins contain the highest concentration of the branched-chain amino acids, especially L-leucine [28]. Sweet and acid dry whey contain 10.3 and 10.5% of leucine, respectively [62]. Leucine acts as the stimulator of the downstream signal control of protein synthesis in the insulin signaling pathway that contributes to the economy of lean tissue proteins (e.g. muscles) as well as maintains a stable level of glucose and low insulin during energy restriction [63]. Leucine enters the brain from the blood more rapidly than any other amino acid [64] and its importance to hypothalamic regulation of food intake has been shown recently. Direct intracerebroventricular injection of either an amino acid mixture (RPMI 1640) or leucine alone (1 µg) suppressed 24 hour food intake indicating that increasing amino acids concentrations within the brain is sufficient to suppress food intake. This effect was related to increased Agrp mRNA levels in GT1-7 hypothalamic cells exposed to low amino acids for 16hrs, however it was attenuated when leucine was removed from cell culture [65]. Such effect can be mediated through the specific hypothalamic nutrient or metabolic sensing neurons [66,67] via the mTOR-dependent mechanism [65] which may be on of the mechanisms by which an increase in brain amino acids concentrations leads to appetite suppression [68].

The high whey content of human milk provides another line of evidence for a role for whey in food intake regulation. The biological importance of interspecies differences in the proportion of whey and casein in milk to growth and development of food intake and metabolic regulation in the newborn has not been defined, but is a potential factor. Milk proteins are the first exogenous alimentary proteins and have many effects in the development of regulatory functions of the gastrointestinal tract, including satiety signals [69]. In addition, breast-fed infants have higher plasma tryptophan (Trp) relative to the branch chain amino acids (BCAA) than formula-fed infants, despite the higher protein concentration of formulas [19]. Because plasma tryptophan uptake by the brain is determined by the plasma ratio of Trp/BCAA and brain tryptophan concentrations influence serotonin synthesis, it can be predicted that breast-fed infants have higher concentrations of brain serotonin, a neurotransmitter know to suppress food intake [70]. Possibly this may explain why breast-fed infants tend to be smaller than formula-fed infants [71].

	Whey Protein and Satiety Hormones

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
There is considerable evidence that the effect of whey proteins on satiety and food intake is mediated by its effect on the release of satiety hormones. Insulin is involved in both short-term and long term regulation of food intake. More than 20 different regulatory peptide hormones are released in the gastro-intestinal (GI) system and many of them are recognized to be involved in the regulation of food intake and are sensitive to gut nutrient content and composition [72]. Many of these hormones respond after protein ingestion and may account for food intake suppression after milk proteins. CCK, GLP-1, GIP, PYY and ghrelin are of current interest.

Insulin release, as noted earlier, is stimulated by the ingestion of whey. In addition to modifying the glycemic response, plasma concentrations of insulin strongly associated with short-term satiety and decreased food intake [73]. In the short-term, insulin response was found to be a stronger correlate of satiety and food intake than the GI hormones.

Cholecystokinin (CCK) is a well established satiety hormone [74], and in rats, CCK and its A subtype receptor are involved in protein-induced food intake suppression [75,76]. In humans, dietary protein and fat are the most important stimulators of CCK secretion [77], and protein digestion is necessary to elicit CCK release [78]. Milk proteins increase CCK concentrations in plasma, peaking initially at 15–20 minutes. After this peak there is a fall and the increase again to approximately 90 min [49,50]. Whey increased CCK more than casein in the Hall [49] but not in the Bowen [50] study, perhaps due to differences in the GMP content of the whey product utilized in the studies. This effect of whey was also found to be similar to soy and gluten proteins [51].

Glucagon-like peptide-1 (GLP-1) may also play a role in milk protein-induced satiety. Both carbohydrate and fat are potent stimulators of GLP-1 [79], but milk proteins stimulate GLP-1 release independently of carbohydrate and fat. However, whey appears to be the stronger and its secretagogue effect might be enhanced in the presence of other macronutrients. A high protein breakfast (58% of total energy) consisting mainly of a dairy products enriched with whey protein isolate resulted in higher GLP-1 concentrations over 3 hours than a high carbohydrate breakfast (19% of total energy from protein) consisting mainly of plain yoghurt (predominantly casein) [80]. Similarly, when protein preloads of 50 g were given with an additional 200 kcal from fat and carbohydrate, whey protein ingestion resulted in higher plasma concentrations of GLP-1 than casein for up to 3 hours in humans [49]. However, with time it may be that casein has a stronger effect than whey in analogy with plasma amino acid concentrations that begin to fall three hours after whey ingestion in humans, but remain elevated for at least 7 hours after casein ingestion [22]. In support of this, plasma GLP-1 concentrations fell substantially 2 hours after the administration of isoenergetic whey, whey hydrolysate and casein hydrolysate solutions, but continued to increase only after the casein solution [81]. Support for an indirect role of GLP-1 in milk-protein induced satiety is provided by studies in rats showing that Exendin-4 (Ex-4), a GLP-1 receptor agonist, interacted with milk proteins to suppress food intake [82,83]. This effect was observed when the protein was given in intact, partially hydrolyzed, or free amino acid forms [83], suggesting that GLP-1-, unlike CCK-induced satiety [84] after protein ingestion does not depend solely on peptides released during digestion. Similarly, in humans, the increase in plasma GLP-1 concentrations was independent of the degree of protein fractionation [81].

Glucose-dependent insulinotropic polypeptide (GIP) is released from K cells in the duodenum after food ingestion and it may play important role in obesity development since it is known that GIP-receptor-knockout mice are resistant to obesity when fed a high-fat diet [72]. Recent studies showed that a whey drink caused significantly enhanced GIP response (+80%) in healthy subjects while branched amino acid mixtures did not have such effect [46]. It is possible that bioactive peptides present in whey or formed during digestion are the primary stimulators of GIP secretion [46].

Peptide YY (PYY) is gut hormone found in L cells throughout the length of the gut, but at higher concentrations in more distal parts [72]. It is secreted postprandially in proportion to caloric load and depends on macronutrient composition [85]. The concentration of PYY in plasma increased after intragastric administration of whey protein or whey peptide hydrolysate to healthy subjects, but it was independent of the degree of protein fractionation [81]. The effect of whey compared with other proteins has not been reported.

Ghrelin is the only orexigenic gut hormone known to date [72]; it is released into circulation from the stomach and its concentrations usually reach a peak just before meals and it is suppressed by food ingestion [86]. Like other gut hormones, the plasma ghrelin response depends on the macronutrient composition of the meal. All 3 classes of macronutrients can suppress plasma ghrelin, but with varying efficacy. The circulating ghrelin response in rodents receiving isocaloric glucose, amino acid, or intralipid infusions into the gastrointestinal tract was examined, and plasma ghrelin was substantially suppressed by all 3 infusions [87]. Complete milk protein, casein, whey or GMP, given by gavage as preloads to rats all lowered plasma ghrelin concentrations similarly at 30 min compared to the water control [60]. In humans, whey protein isolate and calcium caseinate suppressed ghrelin concentrations similar to lactose, but more than glucose over 3 hours, an effect that was correlated with the greater suppression in subsequent energy intake [50]. Whey, soy and gluten proteins also decreased ghrelin similarly over three hours [51].

The form in which proteins reach the small intestine affects the rate of gastric secretion and release of GI-hormones. For example, hydrolysates obtained from either whey protein or casein elicited about 50% more gastric secretion than the whole protein solutions and it was accompanied by increased GIP in plasma during the first 20 min of gastric emptying [81].

	Whey Proteins: Do They Have a Role in High Protein Diets?

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
In 2005 the Dietary Guidelines for Americans recommend three servings per day of milk and milk products [88]. Canada's Food Guide released in 2007 recommends two servings (500 ml) of milk and alternatives per day for children (2–8 y) and adults (19–50 y), three servings for adults (51+ y), and three-four servings for teens (14–18 y) [89]. The role of dairy products per se and their components in body weight maintenance and weight loss is an area of current interest and some controversy [90]. However, an increased intake of dairy proteins including whey may have a role in contributing to the benefits of high protein diets. It has been proposed than one solution for the prevention of obesity is to increase in the protein content of the food supply to provide 20–30%, rather than the current 14–18%, of energy [91].

High-protein diets are popular among the public for their weight loss effect. Although high protein diets aimed at weight loss are high in fat as well as protein and have been criticized for that reason, a recent study found that the Atkins’ diet (high protein and high fat) compared with the Zone, Ornish and LEARN diets had benefits to 12 months in overweight premenopausal women [92]. However, it is also clear that a benefit to high protein diets occurs with more balanced intakes of carbohydrate. A recent study reported that a isocaloric high protein diet (30% protein, 20% fat, and 50% carbohydrate) markedly increased satiety and decreased energy intake and body weight and body fat [13]. A long-term, strictly controlled dietary intervention with succeeding 2 year follow up revealed that a high-protein (25% of energy) fat-reduced (30% of energy) diet promoted greater weight loss after 6 and up to 12 months and provided better long-term (after 1 year) maintenance of reduced intra-abdominal fat stores [93].

High-protein diet-induced thermogenesis is also the factor contributing to body weight regulation [94]. Among macronutrients, proteins are more thermogenic, however not only protein quantity but also quality is essential. Thus, the diet (20% energy from protein) with predominantly animal proteins (14.5%) was more thermogenic compared to the diet with soy protein as predominant source of protein [95]. These results correspond with another study where 24 hour energy expenditure was higher with pork meat than with soy or carbohydrates [96] although this does not seem to have been investigated for milk proteins.

Even a small increase in the protein content of the diet has been shown to be of benefit. It was shown that the higher protein intake (18% vs 15% of energy) reduces weight regain during 6 months after a weight loss of 5–10% in overweight subjects followed a very-low-energy diet for 4 weeks. Weight regain in the higher protein group was associated to only fat-free mass [97]. Similarly, another study showed that during weight management (3 months after 4 weeks of very-low-energy diet) the group with 18 en% protein intake showed a 50% lower body weight regain only consisting of fat-free mass, a 50% decreased energy efficiency, and increased satiety compared to 15 en% protein intake group [98].

Although not determined in humans, the result of animal studies suggests that whey protein may be preferred as an additive source of protein to increase the protein content of diets. When high protein diets (40%) were provided to rats, those fed an -lactalbumin-based diet depressed their food intake by 52.5% during a 3-hour period, but rats offered a casein-based diet depressed their food intake by only 34.3%. Rats fed soy protein, egg white and protein mixture increased their food intake [99]. Another study with insulin-resistant rats showed a 4% decrease in weight gain of those animals fed with a high protein diet containing whey protein concentrate while the diet formulated with kangaroo red meat protein did not, although both high-protein diets (320 g protein/kg diet) reduced food intake and fat mass compared to diets with lower content of protein (80 g protein/kg diet) [100]. Whey protein concentrate reduced plasma insulin by 40% and increased insulin sensitivity, compared to kangaroo meat [100]. In addition, increased DNA damage in rat colonocytes was observed after casein-based and soy-based high protein (25%) diets, while whey-based high protein diet did not cause DNA damage [101]. It is fortunate that safety of high intakes of whey is supported by these data because large quantities of whey are being consumed from commercial source based on their claims of benefit for building muscle mass and for weight (fat) reduction [102].

	Conclusions

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
In conclusion, whey 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. The role of individual whey proteins and peptides remains unclear. The physiologic effects of whey may be mediated by individual whey proteins peptide fractions, or amino acids or by synergistic actions among them, possibly potentiated by other milk constituents.

However, the favourable effects of whey on food intake, subjective satiety and intake regulatory mechanisms in humans have been usually observed in short-term experiments where the components were consumed in amounts much higher than that found in usual serving sizes of dairy products. Thus, it remains unclear if usual consumption of dairy products has any direct effect on satiety beyond the energy that they contain and if whey contributes to the association found between the consumption of dairy products and body weight.

	FOOTNOTES

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 
This paper was presented at the Institute of Food Technologists Annual Meeting, June 24 - 28, Orlando, Florida, 2006.

Disclosure: The presentation was sponsored by the National Dairy Council.

Received September 17, 2007.

	REFERENCES

TOP FOOTNOTES ABSTRACT Introduction Whey Proteins: Nomenclature and... Physiologic Functionality of... Whey Proteins: Physiologic... Whey Protein and Food... Whey Protein and Satiety... Whey Proteins: Do They... Conclusions REFERENCES

 

1. Anderson GH, Aziz A, Abou Samra R: Physiology of food intake regulation: interaction with dietary components. Nestle Nutr Workshop Ser Pediatr Program58 :133 –143; discussion 143–145,2006 .[Medline]
2. Ranganathan R, Nicklas TA, Yang SJ, Berenson GS: The nutritional impact of dairy product cons umption on dietary intakes of adults (1995-1996): the Bogalusa Heart Study. J Am Diet Assoc105 :1391 –1400,2005 .[Medline]
3. Rajpathak SN, Rimm EB, Rosner B, Willett WC, Hu FB: Calcium and dairy intakes in relation to long-term weight gain in US men. Am J Clin Nutr83 :559 –566,2006 .[Abstract/Free Full Text]
4. Barr SI, McCarron DA, Heaney RP, Dawson-Hughes B, Berga SL, Stern JS, Oparil S: Effects of increased consumption of fluid milk on energy and nutrient intake, body weight, and cardiovascular risk factors in healthy older adults. J Am Diet Assoc100 :810 –817,2000 .[Medline]
5. Phillips SM, Bandini LG, Cyr H, Colclough-Douglas S, Naumova E, Must A: Dairy food consumption and body weight and fatness studied longitudinally over the adolescent period. Int J Obes Relat Metab Disord27 :1106 –1113,2003 .[Medline]
6. Heaney RP, Davies KM, Barger-Lux MJ: Calcium and weight: clinical studies. J Am Coll Nutr21 :152S –155S,2002 .[Abstract/Free Full Text]
7. Zemel MB: Role of calcium and dairy products in energy partitioning and weight management. Am J Clin Nutr79 :907S –912S,2004 .[Abstract/Free Full Text]
8. St-Onge MP, Jones PJ: Greater rise in fat oxidation with medium-chain triglyceride consumption relative to long-chain triglyceride is associated with lower initial body weight and greater loss of subcutaneous adipose tissue. Int J Obes Relat Metab Disord27 :1565 –1571,2003 .[Medline]
9. Wang YW, Jones PJ: Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes Relat Metab Disord28 :941 –955,2004 .[Medline]
10. Aziz A, Anderson GH: The effect of dairy components on food intake and satiety: mechanisms of actions and implications for the development of functional foods. In Saarela M (ed): "Functional Dairy Products." Cambridge, UK: Woodhead Publishing Limited, vol.2,2007 .
11. Anderson GH, Moore SE: Dietary proteins in the regulation of food intake and body weight in humans. J Nutr134 :974S –979S,2004 .[Abstract/Free Full Text]
12. Skov AR, Toubro S, Ronn B, Holm L, Astrup A: Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity. Int J Obes Relat Metab Disord23 :528 –536,1999 .[Medline]
13. Weigle DS, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, Purnell JQ: A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr82 :41 –48,2005 .[Abstract/Free Full Text]
14. Manso MA, Lopez-Fandino R: kappa-Casein macropeptides from cheese whey: Physicochemical, biological, nutritional, and technological features for possible uses. Food Reviews International20 :329 –355,2004 .
15. Farrell HM, Jr., Jimenez-Flores R, Bleck GT, Brown EM, Butler JE, Creamer LK, Hicks CL, Hollar CM, Ng-Kwai-Hang KF, Swaisgood HE: Nomenclature of the proteins of cows’ milk-sixth revision. J Dairy Sci87 :1641 –1674,2004 .[Abstract/Free Full Text]
16. Yalcin AS: Emerging therapeutic potential of whey proteins and peptides. Curr Pharm Des12 :1637 –1643,2006 .[Medline]
17. Brody EP: Biological activities of bovine glycomacropeptide. Br J Nutr84(Suppl 1) :S39 –S46,2000 .
18. Fox PF, McSweeney PLH: "Dairy Chemistry and Biochemistry". London: Blackie Academic & Professional,1998 .
19. Lien EL: Infant formulas with increased concentrations of alpha-lactalbumin. Am J Clin Nutr77 :1555S –1558S,2003 .[Abstract/Free Full Text]
20. Whey Products - Definition, Composition and Functions. Reference Manual for U.S. Whey and Lactose Products. U.S. Dairy Export Council, 2004. Available at: [http://www.usdec.org/files/pdfs/US08D_04.pdf] Accessed May 2,2007 .
21. Burrington K: Functional properties of whey products. Reference Manual for U.S. Whey and Lactose Products. U.S. Dairy Export Council, 2004. Available at: [http://www.usdec.org/files/pdfs/US08D_07.pdf] Accessed May 2,2007 .
22. Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrere B: Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci USA94 :14930 –14935,1997 .[Abstract/Free Full Text]
23. Dangin M, Boirie Y, Guillet C, Beaufrere B: Influence of the protein digestion rate on protein turnover in young and elderly subjects. J Nutr132 :3228S –333S,2002 .[Abstract/Free Full Text]
24. Lacroix M, Bos C, Leonil J, Airinei G, Luengo C, Dare S, Benamouzig R, Fouillet H, Fauquant J, Tome D, Gaudichon C: Compared with casein or total milk protein, digestion of milk soluble proteins is too rapid to sustain the anabolic postprandial amino acid requirement. Am J Clin Nutr84 :1070 –1079,2006 .[Abstract/Free Full Text]
25. Korhonen HJ: Technological and health aspects of bioactive components of milk. Int Dairy J16 :1227 –1228,2006 .
26. Nutritional Products Applications for Whey Products. Reference Manual for U.S. Whey and Lactose Products. U.S. Dairy Export Council, 2004. Available at: [http://www.usdec.org/files/pdfs/US08D_16.pdf] Accessed May 2,2007 .
27. Etzel MR: Manufacture and use of dairy protein fractions. J Nutr134 :996S –1002S,2004 .[Abstract/Free Full Text]
28. Walzem RL, Dillard CJ, German JB: Whey components: millennia of evolution create functionalities for mammalian nutrition: what we know and what we may be overlooking. Crit Rev Food Sci Nutr42 :353 –375,2002 .[Medline]
29. Kitts DD, Weiler K: Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery. Curr Pharm Des9 :1309 –1323,2003 .[Medline]
30. Marshall K: Therapeutic applications of whey protein. Altern Med Rev9 :136 –156,2004 .[Medline]
31. Korhonen HJ, Pihlanto A: Bioactive peptides: Production and functionality. Int Dairy J16 :945 –960,2006 .
32. Meisel H: Multifunctional peptides encrypted in milk proteins. Biofactors21 :55 –61,2004 .[Medline]
33. Hartmann R, Meisel H: Food-derived peptides with biological activity: from research to food applications. Curr Opin Biotechnol18 :163 –169,2007 .[Medline]
34. Satake M, Enjoh M, Nakamura Y, Takano T, Kawamura Y, Arai S, Shimizu M: Transepithelial transport of the bioactive tripeptide, Val-Pro-Pro, in human intestinal Caco-2 cell monolayers. Biosci Biotechnol Biochem66 :378 –384,2002 .[Medline]
35. Shimizu M, Tsunogai M, Arai S: Transepithelial transport of oligopeptides in the human intestinal cell, Caco-2. Peptides18 :681 –687,1997 .[Medline]
36. Zemel MB: Mechanisms of dairy modulation of adiposity. J. Nutr133 :252S –256S,2003 .[Abstract/Free Full Text]
37. Pupovac J, Anderson GH: Dietary peptides induce satiety via cholecystokinin-A and peripheral opioid receptors in rats. J Nutr132 :2775 –2780,2002 .[Abstract/Free Full Text]
38. Froetschel MA, Azain MJ, Edwards GL, Barb CR, Amos HE: Opioid and cholecystokinin antagonists alleviate gastric inhibition of food intake by premeal loads of casein in meal-fed rats. J Nutr131 :3270 –3276,2001 .[Abstract/Free Full Text]
39. Cancello R, Clement K: Is obesity an inflammatory illness? Role of low-grade inflammation and macrophage infiltration in human white adipose tissue. Bjog113 :1141 –1147,2006 .[Medline]
40. Boos CJ, Lip GY: Is hypertension an inflammatory process? Curr Pharm Des12 :1623 –1635,2006 .[Medline]
41. Kume H, Okazaki K, Sasaki H: Hepatoprotective effects of whey protein on D-galactosamine-induced hepatitis and liver fibrosis in rats. Biosci Biotechnol Biochem70 :1281 –1285,2006 .[Medline]
42. Nilsson M, Stenberg M, Frid AH, Holst JJ, Bjorck IM: Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. Am J Clin Nutr80 :1246 –1253,2004 .[Abstract/Free Full Text]
43. Pereira MA, Jacobs DR Jr, Van Horn L, Slattery ML, Kartashov AI, Ludwig DS: Dairy consumption, obesity, and the insulin resistance syndrome in young adults: the CARDIA Study. JAMA287 :2081 –2099,2002 .[Abstract/Free Full Text]
44. Dangin M, Boirie Y, Garcia-Rodenas C, Gachon P, Fauquant J, Callier P, Ballevre O, Beaufrere B: The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol-Endocrinol Metabol280 :E340 –E348,2001 .
45. Frid AH, Nilsson M, Holst JJ, Bjorck IM: Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am J Clin Nutr82 :69 –75,2005 .[Abstract/Free Full Text]
46. Nilsson M, Holst JJ, Bjorck IM: Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am J Clin Nutr85 :996 –1004,2007 .[Abstract/Free Full Text]
47. Anderson GH, Tecimer SN, Shah D, Zafar TA: Protein source, quantity, and time of consumption determine the effect of proteins on short-term food intake in young men. J Nutr134 :3011 –3015,2004 .[Abstract/Free Full Text]
48. Moore SE: The effects of milk proteins on the regulation of short-term food intake and appetite in young men. Thesis (M.Sc.)-University of Toronto,2004 .
49. Hall WL, Millward DJ, Long SJ, Morgan LM: Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr89 :239 –248,2003 .[Medline]
50. Bowen J, Noakes M, Trenerry C, Clifton PM: Energy intake, ghrelin, and cholecystokinin after different carbohydrate and protein preloads in overweight men. J Clin Endocrinol Metab91 :1477 –1483,2006 .[Abstract/Free Full Text]
51. Bowen J, Noakes M, Clifton PM: Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake. J Clin Endocrinol Metab91 :2913 –2919,2006 .[Abstract/Free Full Text]
52. Stan E, Chernikov MP: Physiological activity of kappa-casein glycomacropeptide. Vopr Med Khim25 :348 –352,1979 .[Medline]
53. Aleinik SI, Stan E, Chernikov MP: Glycopeptide obtained from k-casein and its effect on protein assimilation. Vopr Pitan(2) :47 –50,1984 .[Medline]
54. Stan EI, Ekimovskii AP, Aleinik SI, Zhuravlev BV: Heterogeneity and physiological activity of bovine k-casein proteolysis products. Vopr Pitan(1) :39 –43,1988 .[Medline]
55. Beucher S, Levenez F, Yvon M, Corring T: Effects of gastric digestive products from casein on CCK release by intestinal cells in rat. J Nutr Biochem5 :578 –584,1994 .
56. Pedersen NL, Nagain-Domaine C, Mahe S, Chariot J, Roze C, Tome D: Caseinomacropeptide specifically stimulates exocrine pancreatic secretion in the anesthetized rat. Peptides21 :1527 –1535,2000 .[Medline]
57. Gustafson DR, McMahon DJ, Morrey J, Nan R: Appetite is not influenced by a unique milk peptide: caseinomacropeptide (CMP). Appetite36 :157 –163,2001 .[Medline]
58. Kelleher SL, Chatterton D, Nielsen K, Lonnerdal B: Glycomacropeptide and alpha-lactalbumin supplementation of infant formula affects growth and nutritional status in infant rhesus monkeys. Am J Clin Nutr77 :1261 –1268,2003 .[Abstract/Free Full Text]
59. Mahe S, Roos N, Benamouzig R, Davin L, Luengo C, Gagnon L, Gausserges N, Rautureau J, Tome D: Gastrojejunal kinetics and the digestion of [15N]beta-lactoglobulin and casein in humans: the influence of the nature and quantity of the protein. Am J Clin Nutr63 :546 –552,1996 .[Abstract/Free Full Text]
60. Peng X: Milk proteins, glycomacropeptide, and regulation of short-term food intake in rats. Thesis (M.Sc.)-University of Toronto,2005 .
61. Hoffman JR, Falvo MJ: Protein - which is best? J Sports Sci Med3 :118 –130,2004 .
62. Glass L, Hedrick T: Nutritional composition of sweet- and acid-type dry wheys. 1. Major factors including amino acids. J Dairy Sci60 :185 –189,1976 .
63. Layman DK, Walker DA: Potential importance of leucine in treatment of obesity and the metabolic syndrome. J Nutr136 :319S –323S,2006 .[Abstract/Free Full Text]
64. Yudkoff M, Daikhin Y, Nissim I, Horyn O, Luhovyy B, Lazarow A: Brain amino acid requirements and toxicity: the example of leucine. J Nutr135 (6 Suppl) :1531S –1538S,2005 .
65. Morrison CD, Xi X, White CL, Ye J, Martin RJ: Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism. Am J Physiol Endocrinol Metab293 :E165 –171,2007 .[Abstract/Free Full Text]
66. Seeley RJ, York DA: Fuel sensing and the central nervous system (CNS): implications for the regulation of energy balance and the treatment for obesity. Obes Rev6 :259 –265,2005 .[Medline]
67. Levin BE: Metabolic sensing neurons and the control of energy homeostasis. Physiol Behav89 :486 –489,2006 .[Medline]
68. Anderson GH: Hunger, appetite, and food intake. In Ziegler EE, Filer LJ (eds):"Present Knowledge in Nutrition," 7th ed. Washington, D.C.: ILSI Press, International Life Sciences Institute, pp13 –18,1996 .
69. Anderson GH, Aziz A: Multifunctional roles of dietary proteins in the regulation of metabolism and food intake: Application to feeding infants. J Pediatr149 :S74 –S79,2006 .
70. Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE: Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs67 :27 –55,2007 .[Medline]
71. Ziegler EE: Growth of breast-fed and formula-fed infants. Nestle Nutr Workshop Ser Pediatr Program58 :51 –59; discussion 59–63,2006 .[Medline]
72. Murphy KG, Bloom SR: Gut hormones and the regulation of energy homeostasis. Nature444 :854 –859,2006 .[Medline]
73. Samra RA, Wolever TM, Anderson GH: Enhanced food intake regulatory responses after a glucose drink in hyperinsulinemic men. Int J Obes (Lond)31 :1222 –1231,2007 .[Medline]
74. Strader AD, Woods SC: Gastrointestinal hormones and food intake. Gastroenterology128 :175 –191,2005 .[Medline]
75. Figlewicz DP, Nadzan AM, Sipols AJ, Green PK, Liddle RA, Porte D Jr, Woods SC: Intraventricular CCK-8 reduces single meal size in the baboon by interaction with type-A CCK receptors. Am J Physiol263(4 Pt 2) :R863 –867,1992 .
76. Miesner J, Smith GP, Gibbs J, Tyrka A: Intravenous infusion of CCKA-receptor antagonist increases food intake in rats. Am J Physiol262(2 Pt 2) :R216 –219,1992 .
77. Liddle RA, Goldfine ID, Rosen MS, Taplitz RA, Williams JA: Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest75 :1144 –1152,1985 .[Medline]
78. Liddle RA: Regulation of cholecystokinin secretion by intraluminal releasing factors. Am J Physiol269(3 Pt 1) :G319 –G327,1995 .
79. Brubaker PL, Anini Y: Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Can J Physiol Pharmacol81 :1005 –1012,2003 .[Medline]
80. Blom WA, Lluch A, Stafleu A, Vinoy S, Holst JJ, Schaafsma G, Hendriks HF: Effect of a high-protein breakfast on the postprandial ghrelin response. Am J Clin Nutr83 :211 –220,2006 .[Abstract/Free Full Text]
81. Calbet JA, Holst JJ: Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans. Eur J Nutr43 :127 –139,2004 .[Medline]
82. Aziz A, Anderson GH: Exendin-4, a GLP-1 receptor agonist, modulates the effect of macronutrients on food intake by rats. J Nutr132 :990 –995,2002 .[Abstract/Free Full Text]
83. Aziz A, Anderson GH: Exendin-4, a GLP-1 receptor agonist, interacts with proteins and their products of digestion to suppress food intake in rats. J Nutr133 :2326 –2330,2003 .[Abstract/Free Full Text]
84. Trigazis L, Orttmann A, Anderson GH: Effect of a cholecystokinin-A receptor blocker on protein-induced food intake suppression in rats. Am J Physiol272(6 Pt 2) :R1826 –R1833,1997 .
85. Cummings DE, Overduin J: Gastrointestinal regulation of food intake. J Clin Invest117 :13 –23,2007 .[Medline]
86. Badman MK, Flier JS: The gut and energy balance: visceral allies in the obesity wars. Science307 :1909 –1914,2005 .[Abstract/Free Full Text]
87. Williams DL, Cummings DE: Regulation of ghrelin in physiologic and pathophysiologic states. J Nutr135 :1320 –1325,2005 .[Abstract/Free Full Text]
88. Huth PJ, DiRienzo DB, Miller GD: Major scientific advances with dairy foods in nutrition and health. J Dairy Sci89 :1207 –1221,2006 .[Abstract/Free Full Text]
89. Canada's Food Guide. How Many Food Guide Servings of Milk and Alternatives Do I Need? Health Canada. Available at: http://www.hc-sc.gc.ca/fn-an/food-guide-aliment/choose-choix/milk-lait/need-besoin/index_e.html Accessed: May 12,2007 .
90. Pfeuffer M, Schrezenmeir J: Milk and the metabolic syndrome. Obes Rev8 :109 –118,2007 .[Medline]
91. Astrup A: The satiating power of protein - a key to obesity prevention? Am J Clin Nutr82 :1 –2,2005 .[Free Full Text]
92. Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, King AC: Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA297 :969 –977,2007 .[Abstract/Free Full Text]
93. Due A, Toubro S, Skov AR, Astrup A: Effect of normal-fat diets, either medium or high in protein, on body weight in overweight subjects: a randomised 1-year trial. Int J Obes Relat Metab Disord28 :1283 –1290,2004 .[Medline]
94. Johnston CS, Day CS, Swan PD: Postprandial thermogenesis is increased 100% on a high-protein, low-fat diet versus a high-carbohydrate, low-fat diet in healthy, young women. J Am Coll Nutr21 :55 –61,2002 .[Abstract/Free Full Text]
95. Pannemans DL, Wagenmakers AJ, Westerterp KR, Schaafsma G, Halliday D: Effect of protein source and quantity on protein metabolism in elderly women. Am J Clin Nutr68 :1228 –1235,1998 .[Abstract]
96. Mikkelsen PB, Toubro S, Astrup A: Effect of fat-reduced diets on 24-h energy expenditure: comparisons between animal protein, vegetable protein, and carbohydrate. Am J Clin Nutr72 :1135 –1141,2000 .[Abstract/Free Full Text]
97. Lejeune MP, Kovacs EM, Westerterp-Plantenga MS: Additional protein intake limits weight regain after weight loss in humans. Br J Nutr93 :281 –289,2005 .[Medline]
98. Westerterp-Plantenga MS, Lejeune MP, Nijs I, van Ooijen M, Kovacs EM: High protein intake sustains weight maintenance after body weight loss in humans. Int J Obes Relat Metab Disord28 :57 –64,2004 .[Medline]
99. Semon BA, Leung PMB, Rogers QR, Gietzen DW: Effect of type of protein on food intake of rats fed high protein diets. Physiology & Behavior41 :451 –458,1987 .[Medline]
100. Belobrajdic DP, McIntosh GH, Owens JA: A high-whey-protein diet reduces body weight gain and alters insulin sensitivity relative to red meat in wistar rats. J Nutr134 :1454 –1458,2004 .[Abstract/Free Full Text]
101. Toden S, Bird AR, Topping DL, Conlon MA: Differential effects of dietary whey, casein and soya on colonic DNA damage and large bowel SCFA in rats fed diets low and high in resistant starch. Br J Nutr97 :535 –543,2007 .[Medline]
102. Cribb PJ, Williams AD, Carey MF, Hayes A: The effect of whey isolate and resistance training on strength, body composition, and plasma glutamine. Int J Sport Nutr Exerc Metab16 :494 –509,2006 .[Medline]

This Article Abstract Full Text (PDF) Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Luhovyy, B. L. Articles by Anderson, G. H. Search for Related Content PubMed PubMed Citation Articles by Luhovyy, B. L. Articles by Anderson, G. H.