Food Proteins or Their Hydrolysates as Regulators of Satiety
2. Protein - Induced Satiety and Food Intake Inhibition — Evidence from
Animal and Human Studies 2.1. High - Protein Preload and High - Protein Meal - Induced Satiety and Food Intake Inhibition
Relatively high - protein diets (meals and diets with on average > 15% of energy from protein are repre-
in most cases exceed feasible and physiologically more sensible amounts for human consumption.
Nevertheless, in humans, several randomized, placebo - controlled intervention studies have shown most frequently comparable, sometimes even supe- rior, effects of high - protein diets (20 – 30% energy from protein) compared with lower - protein diets on weight loss, preservation of lean body mass, and satiety in humans (Westerterp - Plantenga et al.
1999 ; Lejeune et al. 2006 ; Johnstone et al. 2008 ; Leidy et al. 2007 ; Veldhorst et al. 2008 ). For example, Westerterp - Plantenga et al. (1999) com- pared the effect of a high - protein, high - carbohydrate diet (30/60/10% energy from protein, carbohydrate, fat) and a normal - protein diet (10/30/60% energy from protein, carbohydrate, fat) on satiety and meta- bolic rate over 24 hours. When in energy balance, the high - protein diet led to higher satiety and lower hunger and appetite over 24 hours compared to the high - carbohydrate, low - fat diet. In a similar experi- mental setup, the same normal - protein diet was compared to a high - protein, high - fat diet (30/40/30%
energy from protein, carbohydrate, fat) (Lejeune et al. 2006 ). The high - protein, high - fat diet showed increased satiety and decreased appetite and hunger over a 24 - hour period similar to the high - protein, low - fat diet (Westerterp - Plantenga et al. 1999 ). In the latter experiment, the content of fat was kept constant, whereas in the earlier experiment protein was exchanged against both carbohydrate and fat, suggesting that the effect on satiety is indeed depen- dent on the high - protein load and not on the exchange with the type of other macronutrients. A study by Johnstone et al. (2008) investigated further whether the amount of carbohydrate modulates satiety and ad libitum food intake in high - protein diets. Giving either a high - protein diet (30% energy from protein) with very low or medium levels of carbohydrate (4 or 35% energy from carbohydrate, respectively) over 4 weeks, they showed that the high - protein, very low - carbohydrate diet was superior in both reducing ad libitum food intake and increasing satiety.
Overall, high - protein diets have repeatedly been shown to induce higher satiety throughout the day with the effect persisting over longer intervention hunger perceptions were compared after a high -
protein lunch and an isocaloric high - carbohydrate lunch. Although increased satiety was observed 30 and 180 minutes postprandially after the high - protein meal, the differences were minor ( < 10 mm on a 100 mm visual analogue scale score) and disap- peared 210 minutes after lunch (Smeets et al. 2008 ).
The absence of a satiety effect of proteins in these studies was perhaps due to a too - long delay between preload (which is the breakfast in this case) and the ad libitum test - meal. Indeed, several authors have shown that the consumption of a preload more than 2 hours before a test - meal does not reduce subse- quent food intake at the test - meal (Porrini et al. 1997 ; Anderson et al. 2004 ). A possible explanation is that the preload is already metabolized and its effect on the food intake control system has dissipated during the long delay between preload and test - meal. This would suggest that the protein preloads infl uence primarily satiation and short - term satiety.
2.2. Satiety and Food Intake Inhibition in High - Protein Diets
A high - protein diet is generally defi ned as a diet in which high - protein meals are offered at each meal lasting over 24 hours. The difference between a high - protein meal and a high - protein diet is that in the latter situation, the subject gets into a condition where his or her respiratory quotient gets close to the foods quotient. In addition, on a high - protein diet metabolic reactions have been fully established (Lejeune et al. 2006 ). A large body of evidence that high - protein diets affect body weight and energy metabolism is coming from animal studies showing reduction in weight gain and increase in lean body mass in response to high - protein feeding. For example, in a rat study, Pichon et al. (2006) demon- strated that the consumption of a high - protein diet (55% of energy from proteins) over several days leads to a physiological relevant reduction in cumu- lative food intake, thereby lowering weight gain and adiposity compared to a normal - protein diet (14%
of energy from proteins).
However, the protein loads used in animal studies are often very high ( > 50% energy from protein) and
of weight, differences in weight loss and body com- position changes between casein and soy treatments were not signifi cant. In general, in most of the human studies, protein sources can differ with respect to their satiety hormone - releasing proper- ties, but this is seldom related to differences in energy intake or satiety feelings. For example, 50 g of liquid whey, soy, and gluten protein preload evoked different responses in postprandial plasma concentrations of GLP - 1, CCK, and ghrelin; but no differences in energy intake of a subsequent meal was observed for the different protein sources (Bowen et al. 2006a, 2006b ).
Satiety is triggered in part by luminal events within the gastrointestinal tract, including activation of nutrient sensing systems for sugar, fat, and pro- teins. As protein is digested into peptides and amino acids upon ingestion, it has been hypothesised that predigested proteins, that is, protein hydrolysates, are more effi cient in stimulating satiety than intact proteins. Indeed, a few in vitro studies testing the effect of protein hydrolysates on satiety hormone secretion illustrate that hydrolysates induce increased concentrations of CCK and GLP - 1 (Cordier - Bussat et al. 1997 ; Foltz et al. 2008 ). This effect has been partly confi rmed in animal studies, but with fewer differences observed than one could have expected based on the in vitro data. For example, intragastric infusion of pea protein hydrolysate reduced signifi - cantly short - term food intake compared to pea protein but had no effect on 24 - hour energy intake (H ä berer et al. submitted ). In the same study, a similar trend was observed for soy and casein hydro- lysates compared to their corresponding proteins.
Additional evidence that hydrolysates stimulate satiety more than intact proteins is given by Aziz and Anderson (2003) . They investigated the interac- tion between a GLP - 1 receptor agonist (Exendin - 4) and proteins (intact proteins, hydrolysates, and a mixture of amino acids) in rats. The ingestion of a preload of hydrolyzed proteins (whey and casein) or of an amino acid mixture led to reduced energy intake 3 hours after administration compared to ingestion of the intact protein. In this study, products of protein digestion seem to be more effi cient in reducing food intake than the corresponding intact periods up to 4 weeks. The safety of high - protein
diets has yet to be determined in longer - term studies.
2.3. Roles of Protein Sources and Types in Protein - Induced Satiety
Different types of proteins may differ in their sati- ety - inducing and food intake - inhibiting properties.
Indeed, several groups have suggested that different protein sources may differently affect food intake or satiety ratings in high - protein diets or high - protein preloads. Particularly, more rapid gastric emptying and postprandial increase in plasma amino acid con- centration is suggested to increase satiety because of a greater stimulatory effect on gastrointestinal hormones such as cholecystokinin (CCK) and GLP - 1. Despite the fact that several studies reported source - dependent and hydrolysis - dependent effects on satiety hormone release in vitro (Cordier - Bussat et al. 1997 ; Foltz et al. 2008 ), so far only a few human studies have examined the effect of protein source and the degree of protein hydrolysis on satiety and food intake (Lang et al. 1998, 1999 ; Hall et al. 2003 ; Anderson et al. 2004 ; Bowen et al.
2006a, 2006b ; Faipoux et al. 2008 ; Diepvens et al.
2008 ). Most evidence that the protein source may play an important role for protein - induced satiety is coming from studies comparing the food intake inhibitory properties of whey and casein. For example, Hall et al. (2003) reported a signifi cantly lower energy intake after a whey protein preload compared with a casein preload. Other studies, however, show less clear results when comparing the satiating properties of different protein sources.
Comparing the effect of casein, gelatine, and soy protein as part of mixed meals on appetite percep- tion and subsequent meal intake, Lang et al. (1999) obtained only weak effects on satiety and failed to show an effect on food intake. The effect of the protein source in high - protein diets on body weight reduction has rarely been compared. Anderson et al.
(2007) evaluated the effect of high - soy and high - casein meal replacement shakes (4 shakes daily, 20 g protein per shake) on body weight reduction and body composition in a 16 - week intervention study.
Although both study groups lost signifi cant amounts
Secretion of CCK occurs in response to food intake by enteric endocrine I - cells that are scattered throughout the mucosa of the small intestine (Cummings and Overduin 2007 ; Little et al. 2005 ).
Basal plasma CCK concentrations are generally in the low picomolar range in most species and increase approximately 5 - to 10 - fold following meal ingestion, with dietary fat and protein shown as the most potent stimulators of CCK release (Douglas et al. 1988 ). It is believed that CCK release by dietary protein is regulated by endogenous, trypsin - sensitive CCK - releasing peptides (Liddle 1995 ), but some studies, both in vivo and in vitro, have found that dietary protein and its peptide react on CCK - producing cells directly to stimulate CCK release (Beucher et al. 1994 ; Cordier - Bussat et al. 1997 ; Nemoz - Gaillard et al. 1998 ). The presence of protein hydrolysate in the duodenum effectively stimulates the release of CCK from endocrine cells, resulting proteins. However, such an effect could not be
reproduced so far in a human intervention study.
Diepvens and co - workers (2008) obtained only subtle effects of pea protein hydrolysate on satiety and hunger perceptions compared to the nonhydro- lyzed protein.
Taken together, these studies demonstrated that proteins from different sources and proteins vs.
protein hydrolysates differ with respect to their satiety hormone - releasing properties. However, considering the total scientifi c evidence, it is not conclusive so far whether the protein source as well as the integrity in humans has a clinical relevant effect on a behavioral response, that is, reduction in food intake and/or perception of satiety.
3. Mechanisms in