Arie G. Nieuwenhuizen

Dose-dependent satiating effect of whey relative to casein or soy.

Dietary protein plays a role in body weight regulation, partly because of its effects on appetite. The objective was to compare the effects of high or normal casein-, soy-, or whey-protein breakfasts on appetite, specific hormones, amino acid responses and subsequent energy intake. Twenty-five healthy subjects (mean+/-SEMBMI:23.9+/-0.3 kg/m2; age:22+/-1 years) received standardized breakfasts: custards with either casein-, soy, or whey-protein with either 10/55/35 (normal) or 25/55/20 (high)En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scales) and amino acid concentrations were determined for 4 h whereas plasma glucose, insulin, active Glucagon-like Peptide 1 (GLP-1), and active ghrelin concentrations were determined for 3 h; the sensitive moment for lunch was determined. Subjects returned for a second set of experiments and received the same breakfasts, ad lib lunch was offered 180 min later; energy intake (EI) was assessed. At 10En%, whey decreased hunger more than casein or soy (p <0.05), coinciding with higher leucine, lysine, tryptophan, isoleucine, and threonine responses (p<0.05). At 25En% there were no differences in appetite ratings. Whey triggered the strongest responses in concentrations of active GLP-1 (p<0.05) and insulin (p<0.05) compared with casein and/or soy. There were no differences in EI. In conclusion, differences in appetite ratings between different proteins appeared at a normal concentration; at 10En% whey-protein decreased hunger more than casein- or soy-protein. At 25En% whey-protein triggered stronger responses in hormone concentrations than casein- or soy-protein. The results suggest that a difference in appetite ratings between types of protein appears when certain amino acids are above and below particular threshold values.

The hypothalamic-pituitary-adrenal-axis in the regulation of energy balance

Human (visceral) obesity is associated with alterations hypothalamus-pituitary-adrenal (HPA) axis functioning. It is however not completely clear whether the HPA axis is causally or co-incidentally related to (visceral) obesity. This review summarizes supporting data of an involvement of the HPA axis in the development of (visceral) obesity. First, several DNA polymorphisms related to HPA axis functioning are correlated to the development of obesity. Second, chronic elevation of circulatory glucocorticoid concentrations, as in Cushings disease, results in increased abdominal adiposity. Third, (visceral) obesity is associated with a diminished capacity of cortisol to suppress its own secretion. HPA axis functioning might affect energy balance through affecting energy intake. Both CRH and cortisol influence physiological, central mechanisms involved in the regulation of food intake. Still, general activation of the HPA axis has shown to have inconsistent effects on food intake in humans. This inconsistency may partially be explained by gender differences, individual differences in the functioning of the HPA axis, as well as differences in attitude towards eating. In particular, women with high scores on dietary restraint are prone to stress-induced hyperphagia. Dietary restraint scores, in turn, are positively correlated to basal and dexamethasone-suppressed cortisol levels, indicating a complex dual relationship between stress, HPA axis functioning, attitude towards eating and the risk for stress-induced hyperphagia. In the Western society, with chronically high ambient levels of stress and the availability of high caloric foods, this relationship may imply a risk for the development of (visceral) obesity and the metabolic syndrome.

Acute Stress-related Changes in Eating in the Absence of Hunger

Obesity results from chronic deregulation of energy balance, which may in part be caused by stress. Our objective was to investigate the effect of acute and psychological stress on food intake, using the eating in the absence of hunger paradigm, in normal and overweight men and women (while taking dietary restraint and disinhibition into account). In 129 subjects (BMI = 24.5 ± 3.4 kg/m2 and age = 27.6 ± 8.8 years), scores were determined on the Three Factor Eating Questionnaire (dietary restraint = 7.2 ± 4.4; disinhibition = 4.5 ± 2.6; feeling of hunger = 3.9 ± 2.6) and State‐Trait Anxiety Inventory (trait score = 31.7 ± 24.2). In a randomized crossover design, the “eating in absence of hunger” protocol was measured as a function of acute stress vs. a control task and of state anxiety scores. Energy intake from sweet foods (708.1 kJ vs. 599.4 kJ, P < 0.03) and total energy intake (965.2 kJ vs. 793.8 kJ, P < 0.01) were significantly higher in the stress condition compared to the control condition. Differences in energy intake between the stress and control condition were a function of increase in state anxiety scores during the stress task (Δ state anxiety scores) (R2 = 0.05, P < 0.01). This positive relationship was stronger in subjects with high disinhibition scores (R2 = 0.12, P < 0.05). Differences in state anxiety scores were a function of trait anxiety scores (R2 = 0.07, P < 0.05). We conclude that acute psychological stress is associated with eating in the absence of hunger, especially in vulnerable individuals characterized by disinhibited eating behavior and sensitivity to chronic stress.

Dietary protein, metabolism, and body-weight regulation: dose–response effects

Body-weight management requires a multifactorial approach. Recent findings suggest that an elevated protein intake seems to play a key role herein, through (i) increased satiety related to increased diet-induced thermogenesis; (ii) its effect on thermogenesis; (iii) body composition; and (iv) decreased energy-efficiency, all of which are related to protein metabolism. Supported by these mechanisms, relatively larger weight loss and subsequent stronger body-weight maintenance have been observed. Increased insulin sensitivity may appear, but it is unclear whether this is due to weight loss or type of diet. The phenomenon of increased satiety is utilized in reduced energy-intake diets, mainly in the ad libitum condition, whereby sustained satiety is achieved with sustained absolute protein intake in grams, despite lower energy intake. Elevated thermogenesis and glucagon-like peptide-1 (GLP-1) appear to play a role in high-protein induced satiety. Under conditions of weight maintenance, a high-protein diet shows a reduced energy efficiency related to the body composition of the body weight regained, that is, in favor of fat-free mass. Indeed, during body-weight loss, as well as during weight regain, a high-protein diet preserves or increases fat-free mass and reduces fat mass and improves the metabolic profile. In the short-term this may be supported by a positive protein and a negative fat balance, through increased fat oxidation. As protein intake is studied under various states of energy balance, absolute and relative protein intake needs to be discriminated. In absolute grams, a normal protein diet becomes a relatively high-protein diet in negative energy balance and at weight maintenance. Therefore, ‘high protein negative energy balance diets’ aim to keep the grams of proteins ingested at the same level as consumed at energy balance, despite lower energy intakes.

Acute stress and food-related reward activation in the brain during food choice during eating in the absence of hunger.

Background:Stress results in eating in the absence of hunger, possibly related to food reward perception.Hypothesis:Stress decreases food reward perception.Aim:Determine the effect of acute stress on food choice and food choice reward-related brain activity.Subjects:Nine females (BMI=21.5±2.2 kg/m2, age=24.3±3.5 years).Procedure:Fasted subjects came twice to randomly complete either a rest or stress condition. Per session, two functional MRI scans were made, wherein the subjects chose the subsequent meal (food images). The rewarding value of the food was measured as liking and wanting. Food characteristics (for example, crispiness, fullness of taste and so on), energy intake, amount of each macronutrient chosen, plasma cortisol and Visual Analog Scale (VAS) hunger and satiety were measured.Results:Fasted state was confirmed by high hunger (80±5 mm VAS). Breakfast energy intake (3±1 MJ) and liking were similar in all conditions. Wanting was lower postprandially (Δ=−0.3 items/category, P<0.01). Breakfast decreased hunger (−42 mm VAS, P<0.01). Postprandially, energy intake (−1.1 MJ), protein intake (−14.7 g) and carbohydrate intake (−32.7 g all P<0.05) were lower. Fat intake was not different (−7.3, P=0.4). Putamen activity was not lower postprandially. Cortisol levels were increased in the stress condition (Area under the curve of cortisol: ΔAUC=+2.2 × 104 nmol min−1 l−1, P<0.05). Satiety was lower after breakfast (−8 mm VAS, P<0.01). Postprandial energy intake, protein intake and carbohydrate intake were relatively higher compared with the rest condition, resulting from more choice for crispiness and fullness of taste (P<0.05). Brain activation was reduced in reward areas: amygdala, hippocampus and cingulate cortex (AUC=−13.33, −1.34, −2.56% blood oxygen level dependent (BOLD) s for choosing breakfast and AUC=−9.31, −1.25, −2.34%BOLD s<0.05 for choosing the second meal). Putamen activation was decreased postprandially (AUC=−1.2%BOLD s, P<0.05).Conclusion:Reward signaling and reward sensitivity were significantly lower under stress, coinciding with increased energy intake from food choice for more crispiness and fullness of taste. The changes in putamen activation may reflect specifically decreased reward prediction sensitivity.

A breakfast with alpha-lactalbumin, gelatin, or gelatin + TRP lowers energy intake at lunch compared with a breakfast with casein, soy, whey, or whey-GMP

BACKGROUND & AIMS Dietary protein plays a role in body weight regulation, partly due to its effects on satiety. The objective was to compare the effects of casein-, soy-, whey-, whey without glycomacropeptide (GMP)-, alpha-lactalbumin-, gelatin-, or gelatin with tryptophan (TRP)-protein breakfasts at two concentrations on subsequent satiety and energy intake (EI). METHODS Twenty-four healthy subjects (mean+/-SEM BMI: 24.8+/-0.5 kg/m(2); age: 25+/-2 years) received a breakfast; a custard with casein, soy, whey, whey-GMP, alpha-lactalbumin, gelatin, or gelatin+TRP as protein source with either 10/55/35 (normal) or 25/55/20 (high) En% protein/carbohydrate/fat in a randomized, single-blind design. At the precedingly determined time point for lunch, 180 min, subjects were offered an ad lib lunch. Appetite profile (Visual Analogue Scales, VAS) and EI were determined. RESULTS Both at the level of 10 and 25 En% from protein, EI at lunch was approximately 20% lower after an alpha-lactalbumin or gelatin (+TRP) breakfast (2.5+/-0.2 MJ) compared with after a casein, soy, or whey-GMP breakfast (3.2+/-0.3 MJ, p<0.05). Appetite ratings at 180 min differed 15-25 mm (approximately 40%, p<0.05) between types of protein. Differences in EI were a function of differences in appetite ratings (R(2)=0.4, p<0.001). CONCLUSIONS Different proteins (alpha-lactalbumin, gelatin, gelatin+TRP) that are approximately 40% more satiating than other proteins (casein, soy, whey, whey-GMP) induce a related approximately 20% reduction of subsequent energy intake.

Effects of complete whey-protein breakfasts versus whey without GMP-breakfasts on energy intake and satiety

AIM To compare the effects of whey versus whey without glycomacropeptide (GMP) in a high and a normal amount of protein in a breakfast custard on satiety and energy intake (EI), taking concentrations of amino acids (AA), glucose, insulin, glucagon-like peptide 1 (GLP-1) and ghrelin into account. METHODS Twenty-five healthy subjects (mean+/-S.E.M., BMI: 23.9+/-0.3 kg/m(2); age: 22+/-1 years) received a breakfast containing whey or whey without GMP as protein type with 10/55/35 or 25/55/20 En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scale, VAS), glucose, insulin, GLP-1, ghrelin and AA concentrations were measured, and the adequate moment for ad libitum lunch was determined based on differences in ghrelin concentration. In a second set of experiments subjects received the same breakfasts; ad libitum lunch was offered at the pre-determined moment. RESULTS After a breakfast with 25 En% protein increases in insulin and GLP-1 and decreases in ghrelin concentrations were larger; increases in satiety ratings were lower than after 10 En% (p<0.05); there was a treatment x time interaction effect on glucose and insulin concentrations (p<0.001). After a breakfast with whey without GMP insulin concentrations were increased more than after whey (p<0.05). EI at lunch was lower after whey than after whey without GMP (2877+/-165 kJ versus 3208+/-178 kJ, p<0.05), coinciding with more increased concentrations of serine, threonine, alanine, alpha-aminobutyric acid and isoleucine (p<0.05). CONCLUSION GMP as a whey-fraction reduced energy intake coinciding with increased concentrations of certain amino acids, irrespective of the concentration of whey-protein. Although between different concentrations of whey-protein differences in hormone responses were observed, these were unrelated to satiety ratings or energy intake.

Comparison of 2 diets with either 25% or 10% of energy as casein on energy expenditure, substrate balance, and appetite profile

BACKGROUND An increase in the protein content of a diet results in an increase in satiety and energy expenditure. It is not clear to what extent a specific type of protein has such effects. OBJECTIVE The objective was to compare the effects of 2 diets with either 25% or 10% of energy from casein (25En% and 10En% casein diets), as the only protein source, on energy expenditure, substrate balance, and appetite profile. DESIGN During a 36-h stay in a respiration chamber, 24 healthy subjects [12 men and 12 women, body mass index (in kg/m(2)) of 22.4 +/- 2.4, age 25 +/- 7 y] received isoenergetic diets according to subject-specific energy requirements: 25En% diet (25%, 20%, and 55% of energy as protein, fat, and carbohydrate, respectively) and 10En% diet (10%, 35%, and 55% of energy as protein, fat, and carbohydrate, respectively) in a randomized crossover design. Three days before the diets began, the subjects consumed a similar diet at home. Energy expenditure, substrate oxidation, and appetite scores were measured. RESULTS The 25En% casein diet resulted in a 2.6% higher 24-h total energy expenditure (9.30 +/- 0.24 compared with 9.07 +/- 0.24 MJ/d; P < 0.01) and a higher sleeping metabolic rate (6.74 +/- 0.16 compared with 6.48 +/- 0.17 MJ/d; P < 0.001) than did the 10En% casein diet. With the 25En% casein diet, compared with the 10En% casein diet, the subjects were in positive protein balance (0.57 +/- 0.05 compared with -0.08 +/- 0.03 MJ/d; P < 0.0001) and negative fat balance (-0.83 +/- 0.14 compared with 0.11 +/- 0.17 MJ/d; P < 0.0001), whereas positive carbohydrate balances were not significantly different between diets. Satiety was 33% higher with the 25En% casein diet than with the 10En% casein diet (P < 0.05). CONCLUSION A 25En% casein diet boosts energy expenditure, protein balance, satiety, and negative fat balance, which is beneficial to body weight management.

Acute effects of breakfasts containing α-lactalbumin, or gelatin with or without added tryptophan, on hunger, 'satiety' hormones and amino acid profiles

Proteins are the most satiating macronutrients. Tryptophan (TRP) may contribute to the satiating effect, as it serves as a precursor for the anorexigenic neurotransmitter serotonin. To address the role of TRP in the satiating properties of dietary protein, we compared three different breakfasts, containing either alpha-lactalbumin (high in TRP), gelatin (low in TRP) or gelatin with added TRP (gelatin+TRP, high in TRP), on appetite. Twenty-four subjects (22-29 kg/m2; aged 19-37 years) received a subject-specific breakfast at t = 0 with 10, 55 and 35 % energy from protein, carbohydrate and fat respectively in a randomised, single-blind design. Hunger, glucagon-like peptide (GLP)-1, ghrelin, amino acid concentrations and energy intake during a subsequent lunch were determined. Suppression of hunger was stronger 240 min after the breakfast with alpha-lactalbumin compared with gelatin and gelatin+TRP. Total plasma amino acid concentrations were lower with alpha-lactalbumin compared with gelatin with or without TRP (from t = 180-240 min). TRP concentrations were higher after alpha-lactalbumin than after gelatin with or without TRP from t = 0-100 min, whereas from t = 100-240 min, TRP concentrations were lower after gelatin than after alpha-lactalbumin and gelatin+TRP. The plasma ratio of TRP to other large neutral amino acids (LNAA) was, only at t = 100 min, lower after gelatin+TRP than after the other breakfasts. Plasma amino acid responses, TRP concentrations and TRP:LNAA ratios were not correlated with hunger. GLP-1 and ghrelin concentrations were similar for all diets. Energy intake during a subsequent lunch was similar for all diets. Summarised, an alpha-lactalbumin breakfast suppresses hunger more than a gelatin or gelatin+TRP breakfast. This cannot be explained by (possible) differences found in TRP concentrations and TRP:LNAA ratios in the breakfasts and in plasma, as well as in circulating total amino acids, GLP-1 and ghrelin.

Associations between a Single Nucleotide Polymorphism of the FTO Gene (rs9939609) and Obesity-Related Characteristics over Time during Puberty in a Dutch Children Cohort

BACKGROUND The influence of single nucleotide polymorphisms (SNP) of the FTO gene has been shown to change over time. OBJECTIVE The aim was to investigate the relationship between a SNP of the FTO gene (rs9939609) and obesity-related characteristics longitudinally during childhood and puberty. DESIGN From 101 children (58 boys and 43 girls), the FTO (rs9939609) genotype and yearly anthropometric data from birth to age 7 yr were determined. From ages 12 to 17 yr, we measured anthropometry, body composition, leptin concentrations, physical activity, hours watching television, and attitude toward eating yearly; parental characteristics were determined as well. RESULTS At age 17 yr, 20% of the children were overweight/obese, and 88% of the overweight/obese children had the A allele in contrast to 45% of the lean children (P < 0.001). The A allele carriers had a higher fat mass index (kilograms per square meter) and higher leptin concentrations (micrograms per liter) during puberty, except at age 14 yr. Multiple regression analyses with body mass index (BMI; kilograms per square meter) as the dependent variable showed that at ages 12 and 17 yr, dietary restraint score, disinhibition score, BMI of the mother, and the FTO A allele significantly contributed to the model (R(2) = 0.29, P < 0.002; and R(2) = 0.39, P < 0.001). At age 14 yr, dietary restraint score, disinhibition score, and leptin concentrations per kilogram of fat mass significantly contributed to the model (R(2) = 0.25; P < 0.02). CONCLUSION The FTO A allele (rs9939609) is associated with higher BMI, fat mass index, and leptin concentrations from the age of 12 yr, whereas the associations show a dip at ages 13-14 yr and become stronger at age 17 yr. The dip is presumably caused by the dominating endocrinological changes at midpuberty.