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CHAPTER 8 The Effects of Casein-, Whey-, and Soy Protein on Satiety, Energy Expenditure, and Body Composition Margriet Veldhorst, MSc, Anneke van Vught, MSc, and Prof. Dr. Margriet Westerterp-Plantenga, PhD Abstract Relatively high-protein diets have come into focus as having the potential to act on the different metabolic targets regulating body weight, via (i) an increased postprandial and postabsorptive satiety, (ii) preservation of fat-free body mass, and (iii) a lower energy efficiency due to increased thermogenesis. Casein, whey, and soy are three important protein sources of the diet that have been shown to be more satiating than controls such as carbohydrates or water. When protein types are compared with each other, whey seems to be more satiating than casein or soy. Consumption of casein, whey, or soy induces changes in specific hormones but every type of protein has its own mechanism inducing satiety, mainly dependent on amino acid content. In the longer term, additional to the satiety effect, a sustained energy expenditure in negative energy balance and a fat-free mass sparing effect, possibly induced by changes in the somatotropic axis, may be responsible for the weight maintenance after weight-loss effects of high-protein diets. Again, amino acid composition is of major importance as the mechanism through which protein may influence energy expenditure and body composition. Long-term consumption of high-protein diets may have adverse effects on the 121 Weight Control and Slimming Ingredients in Food Technology Susan S. Cho © 2010 Blackwell Publishing. ISBN: 978-0-813-81323-3

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CHAPTER 8

The Effects of Casein-,Whey-, and Soy Protein onSatiety, EnergyExpenditure, andBody Composition

Margriet Veldhorst, MSc, Anneke van Vught, MSc, andProf. Dr. Margriet Westerterp-Plantenga, PhD

Abstract

Relatively high-protein diets have come into focus as having the potential toact on the different metabolic targets regulating body weight, via (i) an increasedpostprandial and postabsorptive satiety, (ii) preservation of fat-free body mass,and (iii) a lower energy efficiency due to increased thermogenesis. Casein, whey,and soy are three important protein sources of the diet that have been shown to bemore satiating than controls such as carbohydrates or water. When protein typesare compared with each other, whey seems to be more satiating than casein or soy.Consumption of casein, whey, or soy induces changes in specific hormones butevery type of protein has its own mechanism inducing satiety, mainly dependenton amino acid content. In the longer term, additional to the satiety effect, asustained energy expenditure in negative energy balance and a fat-free masssparing effect, possibly induced by changes in the somatotropic axis, may beresponsible for the weight maintenance after weight-loss effects of high-proteindiets. Again, amino acid composition is of major importance as the mechanismthrough which protein may influence energy expenditure and body composition.Long-term consumption of high-protein diets may have adverse effects on the

121Weight Control and Slimming Ingredients in Food Technology Susan S. Cho© 2010 Blackwell Publishing. ISBN: 978-0-813-81323-3

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122 Protein based ingredients

kidneys and on blood pressure in at-risk populations such as diabetics or thosewith existing renal disease. In healthy individuals, relatively high protein intakedoes not seem to have serious adverse effects.

Background

Overweight and obesity are rapidly growing into a threat with epidemicproportions and are the result of a positive energy balance, which ariseswhen energy intake exceeds energy expenditure. The solution for theproblem of overweight and obesity in humans is body weight maintenanceafter body weight loss. Conditions for successful weight maintenance are(i) sustained satiety despite a negative energy balance, (ii) sustained basalenergy expenditure despite body weight loss due to (iii) sparing of fat-free mass, since fat-free mass is the main determinant of basal energyexpenditure.

In the context of research on prevention and treatment of overweight andobesity, relatively high-protein diets have come into focus as having thepotential to act on the different metabolic targets regulating body weight.High protein intake has been shown to play a role during weight lossas well as during weight maintenance thereafter through (i) an increasedpostprandial and postabsorptive satiety, (ii) preservation of fat-free bodymass, and (iii) a lower energy efficiency due to increased thermogenesis.A hierarchy has been observed for the satiating properties of the threedifferent macronutrients protein, carbohydrate, and fat, with protein beingthe most satiating and fat the least. A dose-dependent satiating effect ofprotein offered acutely, that is, in a single meal, has been shown in subjectswho are in energy balance and are weight stable. In addition, persistentprotein-induced satiety has been shown when a high-protein diet wasgiven for 24 hours up to several days. Usually mixed proteins are used, forinstance from meat, fish, plants, or dairy products. In terms of satiatingproperties, however, it is important to distinguish between types of proteinsince differences have been shown between different types of protein. Thischapter focuses on the comparison of the acute meal-induced and medium-term diet-induced satiating properties of three different types of protein,that is, casein, whey, and soy. In addition, other factors through whichprotein plays a role in weight loss and weight maintenance are discussed.

Types of Protein

Casein, whey, and soy are three important protein sources of the diet;together they make up a large part of the total daily protein intake. Casein

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and whey are derived from milk or other dairy products; soy is a vegetableprotein source that is derived from soybeans.

Casein

Casein is an important part of milk protein; it comprises ∼80% of theprotein content of bovine milk. It is considered as a “slow” protein becauseit coagulates in the stomach and delays gastric emptying.

Whey

Whey protein is the other primary source of milk protein; ∼20% ofmilk protein is whey. The components of whey include β-lactoglobulin,α-lactalbumin, and glycomacropeptide (GMP). Whey is a popular dietaryprotein supplement suggested to provide immune modulation, improvedmuscle strength and body composition, and to prevent cardiovasculardisease and osteoporosis. In comparison with casein, it is considered as arelatively “fast” protein and therefore has been suggested to induce satietyquickly. The bioactive peptide GMP has been suggested to decrease foodintake.

Soy

Despite being a vegetable protein, soy is considered as a completeprotein since it contains all essential amino acids. Soy-containing diets aresuggested to have health promoting effects, such as lowering of cholesteroland protective effects against obesity, diabetes, and kidney disease.

Short-Term Effects of Casein, Whey,and Soy on Satiety

Casein, whey, and soy have been shown to be more satiating than con-trols such as water or carbohydrates, and there are several studies thathave compared the satiating properties of these types of protein with eachother. There are a few methods to determine effects on satiety, includingmeasurement of (i) appetite ratings, (ii) orexigenic and anorexigenic hor-mones, amino acids, and/or other metabolites, and (iii) ad libitum foodintake.

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Methods to Determine Satiety

Appetite ratings are measured with visual analogue scales asking ques-tions like “How hungry do you feel?” “How satiated do you feel?” “Howfull do you feel?” and “How is your desire to eat?” Subjects are instructedto rate themselves on a 100-mm horizontal line anchored with “not at all”and “extremely.”

Orexigenic and anorexigenic hormones that are involved in appetiteregulation and that are often measured are ghrelin, glucagon-like peptide1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY), and insulin.

The third method to measure effects on satiety is to offer subjects anad libitum meal after a previous, subject-specific fixed meal, and instructthem to eat till they are comfortably full. The amount of food consumedfrom the ad libitum meal has to be measured and provides informationon the satiety induced by the previous fixed meal relative to a previouscontrol meal.

Effects of Casein, Whey, and Soy on Satiety

When casein and whey were at breakfast as 1.7 MJ with 48 g of one ofthe protein types, there was a reduced desire to eat after the whey break-fast compared with the casein breakfast (Hall et al., 2003). In a similarexperiment, however, these results could not be replicated; no differencesbetween casein and whey in breakfasts, with respect to subsequent ap-petite ratings, appetite regulatory hormones, or ad libitum food intake,were observed (Bowen et al., 2006b). Whey and soy reduced ad libitumfood intake to the same extend 3 hours after a 1.1 MJ liquid consump-tion with 50 g whey or soy. In addition, no differences in postprandialghrelin, GLP-1, insulin, and CCK concentrations were observed (Bowenet al., 2006a). Drinks with 45–50 g whey or soy decreased food intake 1hour later compared with control (Anderson et al., 2004). Also, no differ-ence was observed after the casein or soy treatment in subsequent satiety,24-hour energy- or macronutrient intakes, or postprandial glucose andinsulin concentrations after a lunch of 5.2 MJ with 22% of energy fromprotein with ∼65% of the protein from casein or soy (Lang et al., 1998).A casein-rich lunch, however, delayed glucose and insulin responses for1.5 hours compared with soy, but there were only weak and inconsistenteffects on hunger and satiety ratings and no effects on 24-hour energy- ormacronutrient intakes (Lang et al., 1999). Whey was more satiating thancasein or soy when offered in a breakfast with 10% of energy from one of

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0

10

20

30

40

50

60

70

0 60 120 180 240

Time

Sat

iety

Casein

Whey

Soy

Figure 8.1. Satiety after a breakfast with either casein-, whey-, or soy protein.(Adapted from Veldhorst et al., 2007.)

the single protein types, whereas there were no differences in satiety be-tween protein types at the level of 25% of energy from protein. Althoughwhey was more satiating than casein or soy at the level of 10% of energyfrom protein, there was no effect on energy intake 3 hours after breakfast(Veldhorst et al., 2007). GMP has been shown to increase pancreatic se-cretion of digestive peptides (Beucher et al., 1994; Pedersen et al., 2000);nevertheless, pure GMP in a beverage with 0.4% or 2.0% GMP had no ef-fect on energy intake of subjective satiety ratings (Gustafson et al., 2001).The presence or absence of GMP in whey also had no remarkable effect onsubsequent satiety, food intake, or CCK release (Burton-Freeman, 2007).In another experiment, however, GMP as part of whey in a breakfastlowered subsequent energy intake at lunch with ∼10% compared with abreakfast with whey without GMP (Veldhorst et al., 2008b) (Fig. 8.1).

Explanations for Differences in Results

Differences in results between experiments comparing the satiatingproperties of different types of protein may have several reasons. First of

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all, the protein content of the preload or the meal is of major importance.In the above-mentioned experiments, protein content ranged from 10 en-ergy% to >90 energy%. A high level of protein, being the most satiatingmacronutrient, induces an elevated satiety response making it impossibleto distinguish between types of protein. Furthermore, not all proteins thatwere used in the experiments were pure proteins; sometimes a mixture ofproteins was tested. The most important factor when studying the effectsof different types of protein on subsequent food intake, however, is thetiming of a test meal. Effects on energy intake can only be observed if thetest meal is offered at a sensitive and relevant moment in time. Differencesin energy intake should not occur too early, because of the irrelevanceof a meal at that moment in a normal, free-living condition, nor too late,since differences in appetite ratings or hormones have then become ex-tinguished. What the most sensitive moment in time is can be differentfor different types of protein, and should be tested beforehand in eachdifferent condition.

Conclusion

Although there are different results reported in literature, one mayconclude that whey is more satiating than casein however without anysignificant effects on food intake. GMP as a whey fraction does seemto reduce food intake compared with whey without GMP. Differencesbetween effects of soy and casein or soy and whey consumption are lesspronounced.

Long-Term Effects of Casein, Whey, and Soy

Several studies have found a continuously higher satiety throughout theday after a high-protein versus a normal-protein diet, for instance, in theenergy balance controlled condition of a respiration chamber (Westerterp-Plantenga et al., 1999a). But also in a situation of negative energy balance,a high-protein diet has been found to induce a sustained satiety (Lejeuneet al., 2006; Westerterp-Plantenga et al., 2006).

Energy expenditure has been shown to be increased after a high-proteindiet for 36 hours compared with a high-fat diet (Lejeune et al., 2006;Westerterp-Plantenga et al., 1999a) as well as in comparison with a normaldiet (Lejeune et al., 2006). Although casein, whey, and soy are high-quality proteins containing essential amino acids, consumption of only

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one type of protein is difficult. Therefore, there have hardly been anystudies comparing the effects of casein, whey, or soy on satiety, energyexpenditure, or body composition in the medium or long term. In oneexperiment, casein and soy both induced a significant weight loss whenthey were offered in a shake three times a day as part of a 16-week energy-restricted diet for obese women, but there were no differences in weightloss or loss of fat mass between casein and soy (Anderson et al., 2007).

Mechanisms of Action

Mechanisms that may contribute to the increased satiety of a high-protein meal or diet are (i) increases in concentrations of certain hormonesor metabolites (i.e., amino acids), (ii) increases in energy expenditure, and(iii) changes in the somatotropic axis leading to beneficial changes in bodycomposition. Differences in satiating properties between different typesof protein can therefore be attributed to protein-specific characteristicsregarding, for instance, amino acid content, rate of absorption, and theability to induce changes in certain hormones or metabolites.

Changes in Concentrations of Hormonesor Metabolites

Coinciding with the increased satiety after a breakfast with whey com-pared with casein, there were increased concentrations of the amino acidsleucine, lysine, tryptophan, isoleucine, and threonine. These amino acidsmay play a role in the satiating effect of whey (Veldhorst et al., 2007,2008a). Moreover, the faster gastric emptying and absorption of wheyresulting in higher postprandial excursions of amino acids compared withcasein is suggested to induce an increased satiety (Hall et al., 2003). This isin line with the amino static theory from Mellinkoff that states that a largerrise in plasma amino acids increases satiety (Mellinkoff et al., 1956). Theslower digestion of casein may also induce reduced or retarded hormoneresponses, as was the case in comparison with soy (Lang et al., 1999).

Consumption of a meal with casein, whey, or soy protein lead to changesin hormones such as insulin, GLP-1, or ghrelin, which, in some cases, weredifferent between the different types of protein (Veldhorst et al., 2008a).These changes in hormones, however, were not related to changes insatiety and are a physiological response to the presence of nutrients but

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do not necessarily have a direct relation with feelings of satiety (Smeetset al., 2008; Veldhorst et al., 2008a).

Energy Expenditure

A high-protein-diet-induced satiety has been shown to be related toelevated energy expenditure (Lejeune et al., 2006). Increased energy ex-penditure implies increased oxygen consumption and an increase in bodytemperature both leading to feeling deprived of oxygen and thus promotesatiety (Westerterp-Plantenga et al., 1999b, 2006). Energy expenditure isdifferent due to different protein types and is mediated by digestion rateand ATP costs of postprandial protein synthesis. Taking into account thestoichiometry of amino acid catabolism and urea synthesis, the energyexpenditure to produce ATP varies per amino acid and hence also per typeof protein (Westerterp-Plantenga et al., 2006).

Body Composition

In the longer term, dietary protein has been shown to have a positiveeffect on body composition; increasing the level of protein increased leanbody mass and reduced body fat (Jean et al., 2001). During weight mainte-nance, protein intake is characterized by a fat-free mass sparing effect andfat mass reducing effect (Westerterp-Plantenga et al., 2004). The effect ofdietary protein on body composition may be mediated by the somatotropiceffects of protein and of some amino acids in particular. The somatotropicaxis, that is, growth hormone (GH)/insulin-like growth factor-1 (IGF-1axis), plays an important role in muscle mass synthesis (Flakoll et al.,2004), regulation of the fat distribution and reducing fat mass (Bengtssonet al., 1992). Dietary protein, for instance soy, as well as some aminoacids, particularly arginine and lysine, have been shown to stimulate thesomatotropic axis (Bengtsson et al., 1992; Hoppe et al., 2004; van Vughtet al., 2008a, 2008bb). Studies suggest that the amino acid compositionis crucial in understanding the mechanism through which protein mayinfluence GH and IGF-1 production in relation to body composition. Milkprotein, for instance, increases IGF-1 concentrations in children, whereasvegetable proteins or meat proteins do not show an effect on IGF-1 (Hoppeet al., 2004). Recently, associations were found between intakes of the spe-cific amino acids arginine and arginine in combination with lysine and thedevelopment of fat-free mass and fat mass in children. Arginine alone or

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Effects of Casein-, Whey-, and Soy Protein 129

FM

GH

Lipolysis

IGF-1 FFMProteinARGARG + LYS

Figure 8.2. Influence of protein and the amino acids arginine (ARG) and lysine(LYS) on fat-free mass (FFM) and fat mass (FM), via growth hormone (GH) andinsulin growth factor 1 (IGF-1).

combined with lower amounts of lysine reduced fat mass gain, and argi-nine combined with high lysine stimulated the fat-free mass development(van Vught et al., 2008c). The interaction between the amino acids sug-gest that the effects of proteins on body composition may consist of theavailable amount and combination of specific amino acids (Fig. 8.2).

Conclusion

Overall, it can be concluded that every type of protein has its ownmechanism inducing satiety, mainly dependent on amino acid content.Consumption of casein, whey, or soy induces changes in certain hor-mones, but these changes do not necessarily have a direct relation withsatiety. In the longer term, additional to the satiety effect, a sustained en-ergy expenditure in negative energy balance and sparing of fat-free masspossibly induced by changes in the somatotropic axis may be responsi-ble for the weight maintenance after weight-loss effects of high-proteindiets.

Safety

Long-term consumption of high-protein diets may have adverse effectson the kidneys and on blood pressure, especially in at-risk populations suchas diabetics or those with existing renal disease. In healthy individuals,relatively high protein intake does not seem to have serious adverse effects(Eisenstein et al., 2002).

Different amino acids may have opposing effects on the kid-neys and blood pressure, dependent on whether they are involved in

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gluconeogenesis and/or ureagenesis or whether they are acidifying. Aminoacids involved in gluconeogenesis and/or ureagenesis may have a bloodpressure lowering effect, whereas acidifying amino acids may have ablood pressure raising effect. Subjects with subclinical renal injury, lowrenal functional mass, or obesity-related conditions will be more sus-ceptible to the blood pressure raising effects than others (Veldhorstet al., 2008a).

Food Supplement Applications

Casein, whey, and soy are often used, alone or in combination witheach other, as protein source in nutritional supplement products to enhancesports performance and building muscle mass. In health stores and on theinternet, numerous products can be found that are claimed to be helpfulfor people who want to increase their muscle mass and muscle strength.Moreover, some companies offer soy protein as a food supplement thatis suggested to be beneficial for weight loss, because of less hunger andbetter glycemic control. Combinations of casein, whey, and/or soy are usedin weight-loss products and diets to enhance satiety and thereby reducefood intake.

Patent Activities

There are some patents on the protein content of body weight controlproducts, for instance, patent MXPA04008476 entitled “Compositionsand methods for treatment of body weight conditions with milk mineralsand casein fractions” or patent FR2889067 entitled “Using protein fractionfrom whey for control of body weight, e.g. to promote slimming, comprisesβ-lactoglobulin, and α-lactalbumin at specified ratio.”

Information on Global Suppliers

Casein and whey protein are supplied by the dairy industry with nu-merous companies offering different forms of casein or whey. Soy proteinis, among others, supplied by The Solae Company and The Central SoyaCompany.

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